[Modern methods of diagnosis dyslipidemia ].

PubMed

Sukhorukov, V N; Karagodin, V P; Orekhov, A N

2016-01-01

Dyslipidemia is abnormalities of lipid and lipoprotein metabolism. Most dyslipidemias are hyperlipidemias; that is an abnormally high level of lipids and/or lipoproteins in the blood. Lipid and lipoprotein abnormalities are common in the general population, and are regarded as a modifiable risk factor for cardiovascular disease due to their influence on atherosclerosis. Primary dyslipidemia is usually due to genetic causes, while secondary dyslipidemia arises due to other underlying causes such as diabetes mellitus. Thus, dyslipidemia is an important factor in the development of atherosclerosis and cardiovascular diseases therefore, it is important to diagnose it in time. This review focuses on the modern methods of diagnosis of dyslipidemia.

Comprehensive genotyping in dyslipidemia: mendelian dyslipidemias caused by rare variants and Mendelian randomization studies using common variants.

PubMed

Tada, Hayato; Kawashiri, Masa-Aki; Yamagishi, Masakazu

2017-04-01

Dyslipidemias, especially hyper-low-density lipoprotein cholesterolemia and hypertriglyceridemia, are important causal risk factors for coronary artery disease. Comprehensive genotyping using the 'next-generation sequencing' technique has facilitated the investigation of Mendelian dyslipidemias, in addition to Mendelian randomization studies using common genetic variants associated with plasma lipids and coronary artery disease. The beneficial effects of low-density lipoprotein cholesterol-lowering therapies on coronary artery disease have been verified by many randomized controlled trials over the years, and subsequent genetic studies have supported these findings. More recently, Mendelian randomization studies have preceded randomized controlled trials. When the on-target/off-target effects of rare variants and common variants exhibit the same direction, novel drugs targeting molecules identified by investigations of rare Mendelian lipid disorders could be promising. Such a strategy could aid in the search for drug discovery seeds other than those for dyslipidemias.

Novel QTLs for HDL levels identified in mice by controlling for Apoa2 allelic effects: confirmation of a chromosome 6 locus in a congenic strain.

PubMed

Welch, Carrie L; Bretschger, Sara; Wen, Ping-Zi; Mehrabian, Margarete; Latib, Nashat; Fruchart-Najib, Jamila; Fruchart, Jean Charles; Myrick, Christy; Lusis, Aldons J

2004-03-12

Atherosclerosis is a complex disease resulting from the interaction of multiple genes, including those causing dyslipidemia. Relatively few of the causative genes have been identified. Previously, we identified Apoa2 as a major determinant of high-density lipoprotein cholesterol (HDL-C) levels in the mouse model. To identify additional HDL-C level quantitative trait loci (QTLs), while controlling for the effect of the Apoa2 locus, we performed linkage analysis in 179 standard diet-fed F(2) mice derived from strains BALB/cJ and B6.C-H25(c) (a congenic strain carrying the BALB/c Apoa2 allele). Three significant QTLs and one suggestive locus were identified. A female-specific locus mapping to chromosome 6 (Chr 6) also exhibited effects on plasma non-HDL-C, apolipoprotein AII (apoAII), apoB, and apoE levels. A Chr 6 QTL was independently isolated in a related congenic strain (C57BL/6J vs. B6.NODc6: P = 0.003 and P = 0.0001 for HDL-C and non-HDL-C levels, respectively). These data are consistent with polygenic inheritance of HDL-C levels in the mouse model and provide candidate loci for HDL-C and non-HDL-C level determination in humans.

Systematic Functional Interrogation of Rare Cancer Variants Identifies Oncogenic Alleles | Office of Cancer Genomics

Cancer.gov

Cancer genome characterization efforts now provide an initial view of the somatic alterations in primary tumors. However, most point mutations occur at low frequency, and the function of these alleles remains undefined. We have developed a scalable systematic approach to interrogate the function of cancer-associated gene variants. We subjected 474 mutant alleles curated from 5,338 tumors to pooled in vivo tumor formation assays and gene expression profiling. We identified 12 transforming alleles, including two in genes (PIK3CB, POT1) that have not been shown to be tumorigenic.

The distribution of apolipoprotein E gene polymorphism in Chinese civil aircrews, and a possible risk factor to their overweight and dyslipidemia is cumulative flight time.

PubMed

Huang, He; Liu, Jing; Feng, Yingjin; Chen, Weiru

2013-02-01

The prevalence of dyslipidemia and overweight is significantly higher in aircrews than that in general population. The purpose of the study was to examine the distribution of APOE gene polymorphism and the influence of which as well as occupational environment on dyslipidemia and overweight in Chinese civil aircrews. APOE gene polymorphism was investigated using PCR-RFLP, plasma lipid parameters were measured by standard enzymatic kits and personal information of the aircrews was collected through questionnaires. The allele frequencies among aircrews were ε2: 17.0%, ε3: 80.9%, and ε4: 2.1%, APOE gene polymorphism was associated with significant differences in TC and LDL-C. E2 individuals had the lowest TC and LDL-C concentrations, and E4 participants had the highest levels (p<0.001). In addition, the TC and LDL-C concentrations, as well as BMI rose with the increasing cumulative flying hours (p<0.05). The further logistic regression analysis showed the significant associations of BMI and dyslipidemia (p<0.0001, OR=2.093), cumulative flight time and overweight (p<0.0001, OR=1.560). The distribution of APOE alleles among aircrews was provided for the first time, which is not fully identical with that among general population. These data also suggested the cumulative flight time influenced dyslipidemia and overweight as an environmental contributor. Copyright © 2012 Elsevier B.V. All rights reserved.

Frequency of Testing for Dyslipidemia: An Evidence-Based Analysis

PubMed Central

2014-01-01

Background Dyslipidemias include high levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides and low levels of high-density lipoprotein (HDL) cholesterol. Dyslipidemia is a risk factor for cardiovascular disease, which is a major contributor to mortality in Canada. Approximately 23% of the 2009/11 Canadian Health Measures Survey (CHMS) participants had a high level of LDL cholesterol, with prevalence increasing with age, and approximately 15% had a total cholesterol to HDL ratio above the threshold. Objectives To evaluate the frequency of lipid testing in adults not diagnosed with dyslipidemia and in adults on treatment for dyslipidemia. Research Methods A systematic review of the literature set out to identify randomized controlled trials (RCTs), systematic reviews, health technology assessments (HTAs), and observational studies published between January 1, 2000, and November 29, 2012, that evaluated the frequency of testing for dyslipidemia in the 2 populations. Results Two observational studies assessed the frequency of lipid testing, 1 in individuals not on lipid-lowering medications and 1 in treated individuals. Both studies were based on previously collected data intended for a different objective and, therefore, no conclusions could be reached about the frequency of testing at intervals other than the ones used in the original studies. Given this limitation and generalizability issues, the quality of evidence was considered very low. No evidence for the frequency of lipid testing was identified in the 2 HTAs included. Canadian and international guidelines recommend testing for dyslipidemia in individuals at an increased risk for cardiovascular disease. The frequency of testing recommended is based on expert consensus. Conclusions Conclusions on the frequency of lipid testing could not be made based on the 2 observational studies. Current guidelines recommend lipid testing in adults with increased cardiovascular risk, with

Body Mass Index Is Better than Other Anthropometric Indices for Identifying Dyslipidemia in Chinese Children with Obesity

PubMed Central

Jing, Jin; Ma, Jun; Chen, Yajun; Li, Xiuhong; Yang, Wenhan; Guo, Li; Jin, Yu

2016-01-01

Background Body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) are used in screening and predicting obesity in adults. However, the best identifier of metabolic complications in children with obesity remains unclear. This study evaluated lipid profile distribution and investigated the best anthropometric parameter in association with lipid disorders in children with obesity. Methods A total of 2243 school children aged 7–17 years were enrolled in Guangzhou, China, in 2014. The anthropometric indices and lipid profiles were measured. Dyslipidemia was defined according to the US Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents. The association between anthropometry (BMI, WC, and WHR) and lipid profile values was examined using chi-square analysis and discriminant function analysis. Information about demography, physical activity, and dietary intake was provided by the participant children and their parents. Results Children aged 10–14 and 15–17 years old generally had higher triglyceride values but lower median concentration of total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol compared with children aged 7–9 years old (all P < 0.001). These lipid parameters fluctuated in children aged 10–14 years old. The combination of age groups, BMI, WC and WHR achieved 65.1% accuracy in determining dyslipidemic disorders. BMI correctly identified 77% of the total dyslipidemic disorders in obese children, which was higher than that by WHR (70.8%) (P< 0.05). Conclusion The distribution of lipid profiles in Chinese children differed between younger and older age groups, and the tendency of these lipid levels remarkably fluctuated during 10 to 14 years old. BMI had better practical utility in identifying dyslipidemia among school-aged children with obesity compared with other anthropometric measures. PMID:26963377

Body Mass Index Is Better than Other Anthropometric Indices for Identifying Dyslipidemia in Chinese Children with Obesity.

PubMed

Zhu, Yanna; Shao, Zixian; Jing, Jin; Ma, Jun; Chen, Yajun; Li, Xiuhong; Yang, Wenhan; Guo, Li; Jin, Yu

2016-01-01

Body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) are used in screening and predicting obesity in adults. However, the best identifier of metabolic complications in children with obesity remains unclear. This study evaluated lipid profile distribution and investigated the best anthropometric parameter in association with lipid disorders in children with obesity. A total of 2243 school children aged 7-17 years were enrolled in Guangzhou, China, in 2014. The anthropometric indices and lipid profiles were measured. Dyslipidemia was defined according to the US Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents. The association between anthropometry (BMI, WC, and WHR) and lipid profile values was examined using chi-square analysis and discriminant function analysis. Information about demography, physical activity, and dietary intake was provided by the participant children and their parents. Children aged 10-14 and 15-17 years old generally had higher triglyceride values but lower median concentration of total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol compared with children aged 7-9 years old (all P < 0.001). These lipid parameters fluctuated in children aged 10-14 years old. The combination of age groups, BMI, WC and WHR achieved 65.1% accuracy in determining dyslipidemic disorders. BMI correctly identified 77% of the total dyslipidemic disorders in obese children, which was higher than that by WHR (70.8%) (P< 0.05). The distribution of lipid profiles in Chinese children differed between younger and older age groups, and the tendency of these lipid levels remarkably fluctuated during 10 to 14 years old. BMI had better practical utility in identifying dyslipidemia among school-aged children with obesity compared with other anthropometric measures.

Development of job standards for clinical nutrition therapy for dyslipidemia patients.

PubMed

Kang, Min-Jae; Seo, Jung-Sook; Kim, Eun-Mi; Park, Mi-Sun; Woo, Mi-Hye; Ju, Dal-Lae; Wie, Gyung-Ah; Lee, Song-Mi; Cha, Jin-A; Sohn, Cheong-Min

2015-04-01

Dyslipidemia has significantly contributed to the increase of death and morbidity rates related to cardiovascular diseases. Clinical nutrition service provided by dietitians has been reported to have a positive effect on relief of medical symptoms or reducing the further medical costs. However, there is a lack of researches to identify key competencies and job standard for clinical dietitians to care patients with dyslipidemia. Therefore, the purpose of this study was to analyze the job components of clinical dietitian and develop the standard for professional practice to provide effective nutrition management for dyslipidemia patients. The current status of clinical nutrition therapy for dyslipidemia patients in hospitals with 300 or more beds was studied. After duty tasks and task elements of nutrition care process for dyslipidemia clinical dietitians were developed by developing a curriculum (DACUM) analysis method. The developed job standards were pretested in order to evaluate job performance, difficulty, and job standards. As a result, the job standard included four jobs, 18 tasks, and 53 task elements, and specific job description includes 73 basic services and 26 recommended services. When clinical dietitians managing dyslipidemia patients performed their practice according to this job standard for 30 patients the job performance rate was 68.3%. Therefore, the job standards of clinical dietitians for clinical nutrition service for dyslipidemia patients proposed in this study can be effectively used by hospitals.

Dyslipidemia in people living with HIV-AIDS in a tertiary hospital in South-East Nigeria.

PubMed

Anyabolu, Ernest Ndukaife

2017-01-01

Across the globe, human immunodeficiency virus (HIV) infection is a healthcare problem. Dyslipidemia, a cardiovascular risk factor, is known to occur with the progression of HIV infection. The factors which influence dyslipidemia in HIV subjects have not been completely identified. The aim of this study was to evaluate serum lipids and identify the factors which might influence dyslipidemia in treatment-naïve HIV subjects in Owerri, Nigeria. This was a cross-sectional study of treatment-naïve HIV subjects. Anthropometric and demographic data were collected. Serum LDL serum cholesterol, serum high density lipoprotein cholesterol, serum triglyceride, spot urine creatinine, spot urine osmolality, spot urine protein, serum creatinine, 24-hour urine protein, 24-hour urine osmolality, 24-hour urine creatinine, creatinine clearance and hemoglobin were conducted. The variables were compared between those who have dyslipidemia and those who have no dyslipidemia. The mean age of the subjects was 39 ± 11 years. Females constituted 72.0% and males 28.0%. Elevated serum LDL was present in 17.6%, elevated serum total cholesterol in 11.4%, elevated serum triglyceride in 9.9% and low serum HDL in 34.4% of the subjects. There was significant association between dyslipidemia and CD4 cells count, as well as anemia. There was no significant association between dyslipidemia and urine protein, urine creatinine, urine osmolality, creatinine clearance, as well as 24-hour urine volume. The prevalence of dyslipidemia was high in the study subjects. Abnormal CD4 cells count and anemia were common in treatment-naïve HIV subjects who have dyslipidemia.

LipidSeq: a next-generation clinical resequencing panel for monogenic dyslipidemias.

PubMed

Johansen, Christopher T; Dubé, Joseph B; Loyzer, Melissa N; MacDonald, Austin; Carter, David E; McIntyre, Adam D; Cao, Henian; Wang, Jian; Robinson, John F; Hegele, Robert A

2014-04-01

We report the design of a targeted resequencing panel for monogenic dyslipidemias, LipidSeq, for the purpose of replacing Sanger sequencing in the clinical detection of dyslipidemia-causing variants. We also evaluate the performance of the LipidSeq approach versus Sanger sequencing in 84 patients with a range of phenotypes including extreme blood lipid concentrations as well as additional dyslipidemias and related metabolic disorders. The panel performs well, with high concordance (95.2%) in samples with known mutations based on Sanger sequencing and a high detection rate (57.9%) of mutations likely to be causative for disease in samples not previously sequenced. Clinical implementation of LipidSeq has the potential to aid in the molecular diagnosis of patients with monogenic dyslipidemias with a high degree of speed and accuracy and at lower cost than either Sanger sequencing or whole exome sequencing. Furthermore, LipidSeq will help to provide a more focused picture of monogenic and polygenic contributors that underlie dyslipidemia while excluding the discovery of incidental pathogenic clinically actionable variants in nonmetabolism-related genes, such as oncogenes, that would otherwise be identified by a whole exome approach, thus minimizing potential ethical issues.

Quantitative trait loci at the 11q23.3 chromosomal region related to dyslipidemia in the population of Andhra Pradesh, India.

PubMed

Pranavchand, Rayabarapu; Reddy, Battini Mohan

2017-06-13

Given the characteristic atherogenic dyslipidemia of south Indian population and crucial role of APOA1, APOC3, APOA4 and APOA5 genes clustered in 11q23.3 chromosomal region in regulating lipoprotein metabolism and cholesterol homeostasis, a large number of recently identified variants are to be explored for their role in regulating the serum lipid parameters among south Indians. Using fluidigm SNP genotyping platform, a prioritized set of 96 SNPs of the 11q23.3 chromosomal region were genotyped on 516 individuals from Hyderabad, India, and its vicinity and aged >45 years. The linear regression analysis of the individual lipid traits viz., TC, LDLC, HDLC, VLDL and TG with each of the 78 SNPs that confirm to HWE and with minor allele frequency > 1%, suggests 23 of those to be significantly associated (p ≤ 0.05) with at least one of these quantitative traits. Most importantly, the variant rs632153 is involved in elevating TC, LDLC, TG and VLDLs and probably playing a crucial role in the manifestation of dyslipidemia. Additionally, another three SNPs rs633389, rs2187126 and rs1263163 are found risk conferring to dyslipidemia by elevating LDLC and TC levels in the present population. Further, the ROC (receiver operating curve) analysis for the risk scores and dyslipidemia status yielded a significant area under curve (AUC) = 0.675, suggesting high discriminative power of the risk variants towards the condition. The interaction analysis suggests rs10488699-rs2187126 pair of the BUD13 gene to confer significant risk (Interaction odds ratio = 14.38, P = 7.17 × 10 5 ) towards dyslipidemia by elevating the TC levels (β = 37.13, p = 6.614 × 10 5 ). On the other hand, the interaction between variants of APOA1 gene and BUD13 and/or ZPR1 regulatory genes at this region are associated with elevated TG and VLDL. The variants at 11q23.3 chromosomal region seem to determine the quantitative lipid traits and in turn dyslipidemia in the population of Hyderabad

Systems genetics identifies a co-regulated module of liver microRNAs associated with plasma LDL cholesterol in murine diet-induced dyslipidemia

USDA-ARS?s Scientific Manuscript database

Chronically altered levels of circulating lipids, termed dyslipidemia, is a significant risk factor for a number of metabolic and cardiovascular morbidities. MicroRNAs (miRNAs) have emerged as important regulators of lipid balance, have been implicated in dyslipidemia, and have been proposed as cand...

Targeted next-generation sequencing in monogenic dyslipidemias.

PubMed

Hegele, Robert A; Ban, Matthew R; Cao, Henian; McIntyre, Adam D; Robinson, John F; Wang, Jian

2015-04-01

To evaluate the potential clinical translation of high-throughput next-generation sequencing (NGS) methods in diagnosis and management of dyslipidemia. Recent NGS experiments indicate that most causative genes for monogenic dyslipidemias are already known. Thus, monogenic dyslipidemias can now be diagnosed using targeted NGS. Targeting of dyslipidemia genes can be achieved by either: designing custom reagents for a dyslipidemia-specific NGS panel; or performing genome-wide NGS and focusing on genes of interest. Advantages of the former approach are lower cost and limited potential to detect incidental pathogenic variants unrelated to dyslipidemia. However, the latter approach is more flexible because masking criteria can be altered as knowledge advances, with no need for re-design of reagents or follow-up sequencing runs. Also, the cost of genome-wide analysis is decreasing and ethical concerns can likely be mitigated. DNA-based diagnosis is already part of the clinical diagnostic algorithms for familial hypercholesterolemia. Furthermore, DNA-based diagnosis is supplanting traditional biochemical methods to diagnose chylomicronemia caused by deficiency of lipoprotein lipase or its co-factors. The increasing availability and decreasing cost of clinical NGS for dyslipidemia means that its potential benefits can now be evaluated on a larger scale.

Antisense therapy and emerging applications for the management of dyslipidemia.

PubMed

Toth, Peter P

2011-01-01

Because a significant percentage of patients who require high-dose statin therapy for dyslipidemia experience treatment-related muscle symptoms and an inconsistent clinical response, alternative or adjunctive approaches to the management of dyslipidemia are needed. One alternative approach, antisense therapy, may offer an effective and well-tolerated option for patients not satisfactorily responsive to or intolerant to standard pharmacologic dyslipidemia therapies. This review provides an overview of antisense technology and its potential role in the management of dyslipidemia. Source material was obtained primarily from the published literature identified through a search of the PubMed database. Antisense technology is an evolving approach to therapy that has gone through a series of refinements to enhance molecular stability, potency, and tolerability. Mipomersen is an antisense molecule capable of producing clinically meaningful reductions in low-density lipoprotein cholesterol in patients with severe familial hypercholesterolemia. Further long-term clinical studies are required to more clearly quantify its impact on risk for cardiovascular events and establish whether it increases risk for hepatosteatosis. Antisense therapy represents a potentially effective and well-tolerated emerging treatment modality for numerous diseases. In the treatment of hypercholesterolemia, the antisense therapy mipomersen may provide a possible treatment option for patients with treatment-resistant dyslipidemia. Copyright © 2011 National Lipid Association. Published by Elsevier Inc. All rights reserved.

[Association between CETP polymorphisms and haplotypes with dyslipidemia in Xinjiang Uygur and Kazak residents].

PubMed

Hu, Y H; Liu, J M; Zhang, M; He, J; Yan, Y Z; Ma, J L; Ma, R L; Guo, H; Rui, D S; Sun, F; Mu, L L; Niu, Q; Ding, Y S; Zhang, J Y; Li, S G; Guo, S X

2016-08-24

To explore the relationship between the polymorphisms and haplotypes in the CETP gene and dyslipidemia among Xinjiang Kazak and Uygur residents. A population status survey was performed from 2010 to 2011 in Kashgar Xinjiang Uygur and Kazak residents, stratified cluster sampling method was used to select Uygur, Kazak residents with abnormal blood lipid values (n=367 and 345, respectively) as the dyslipidemia groups, and to select residents with normal lipid values as control group from the same area (n=374 and 390, respectively). SNaPshot technology was applied to detect the DNA of CETP gene rs3764261, rs1800775, rs708272 and rs5882 loci in all selected residents, and linkage disequilibrium analysis and haplotype construction were performed. (1) In Uygur residents, the dyslipidemia risk of rs708272 CT (OR=0.64, 95%CI 0.46-0.91, P=0.01) and TT genotype (OR=0.60, 95%CI 0.40-0.91, P=0.02) was significantly lower than CC genotype. Dyslipidemia risk of rs3764261 GT (OR=0.55, 95%CI 0.40-0.74, P=0.00) and TT genotype (OR=0.47, 95%CI 0.28-0.78, P<0.01) was significantly lower than GG genetype. Dyslipidemia risk of the rs1800775 CC genotype was higher than AA genotype (OR=1.79, 95%CI 1.17-2.74, P=0.01). There was no statistical significance in CETP gene of the 4 genotype and allele frequency between the dyslipidemia and normal lipid groups in Kazak residents (all P>0.05). (2) In Uighur residents with dyslipidemia, HDL-C level was significantly higher in rs708272 TT genotype carriers than in CC and CT genotypes (all P<0.05) and in rs3764261 TT genotype carriers than in GG genotype carriers (P=0.008), while was significantly lower in rs1800775 CC genotype carriers with AA genotype carriers (P=0.008). (3) Linkage disequilibrium analysis showed that there was strong linkage disequilibrium between rs3764261 and rs708272 (D'=0.869, r(2)=0.869), rs1800775 and rs708272 (D'=0.845, r(2)=0.446) in Uighur residents, and there was strong linkage disequilibrium between rs3764261 and rs

Managing mixed dyslipidemia in special populations.

PubMed

Miller, Michael

2010-01-01

Controlling low-density lipoprotein cholesterol is one of the major focuses of cardiovascular care. However, the twin global pandemics of obesity and diabetes are promoting an increased prevalence of associated cardiometabolic risk factors. These factors include mixed dyslipidemia, which is prevalent among several important subgroups of the overall population. Cardiovascular risk increases as women reach and extend beyond menopause, partly reflective of dyslipidemia. In addition, women with polycystic ovary syndrome display a cluster of risk factors reminiscent of the metabolic syndrome. Certain ethnic groups are also at increased risk for type 2 diabetes or the metabolic syndrome. Dyslipidemia contributes significantly to overall cardiovascular risk in the elderly, and the frequency of children and adolescents presenting with type 2 diabetes or metabolic syndrome is increasing worldwide. Physicians should be aware of the possibility of mixed dyslipidemia in patients at elevated cardiometabolic risk. However, while combination therapy may successfully correct the associated dyslipidemia, it remains to be established whether the addition of a second agent improves coronary risk beyond statin monotherapy.

LipidSeq: a next-generation clinical resequencing panel for monogenic dyslipidemias[S

PubMed Central

Johansen, Christopher T.; Dubé, Joseph B.; Loyzer, Melissa N.; MacDonald, Austin; Carter, David E.; McIntyre, Adam D.; Cao, Henian; Wang, Jian; Robinson, John F.; Hegele, Robert A.

2014-01-01

We report the design of a targeted resequencing panel for monogenic dyslipidemias, LipidSeq, for the purpose of replacing Sanger sequencing in the clinical detection of dyslipidemia-causing variants. We also evaluate the performance of the LipidSeq approach versus Sanger sequencing in 84 patients with a range of phenotypes including extreme blood lipid concentrations as well as additional dyslipidemias and related metabolic disorders. The panel performs well, with high concordance (95.2%) in samples with known mutations based on Sanger sequencing and a high detection rate (57.9%) of mutations likely to be causative for disease in samples not previously sequenced. Clinical implementation of LipidSeq has the potential to aid in the molecular diagnosis of patients with monogenic dyslipidemias with a high degree of speed and accuracy and at lower cost than either Sanger sequencing or whole exome sequencing. Furthermore, LipidSeq will help to provide a more focused picture of monogenic and polygenic contributors that underlie dyslipidemia while excluding the discovery of incidental pathogenic clinically actionable variants in nonmetabolism-related genes, such as oncogenes, that would otherwise be identified by a whole exome approach, thus minimizing potential ethical issues. PMID:24503134

Dyslipidemia in HIV Infected Children Receiving Highly Active Antiretroviral Therapy.

PubMed

Mandal, Anirban; Mukherjee, Aparna; Lakshmy, R; Kabra, Sushil K; Lodha, Rakesh

2016-03-01

To assess the prevalence of dyslipidemia and lipodystrophy in Indian children receiving non-nucleoside reverse transcriptase inhibitor (NNRTI) based highly active antiretroviral therapy (HAART) and to determine the associated risk factors for the same. The present cross-sectional study was conducted at a Pediatric Clinic of a tertiary care teaching center in India, from May 2011 through December 2012. HIV infected children aged 5-15 y were enrolled if they did not have any severe disease or hospital admission within last 3 mo or receive any medications known to affect the lipid profile. Eighty-one children were on highly active antiretroviral therapy (HAART) for at least 6 mo and 16 were receiving no antiretroviral therapy (ART). Participants' sociodemographic, nutritional, clinical, and laboratory data were recorded in addition to anthropometry and evidence of lipodystrophy. Fasting lipid profile, apolipoprotein A1 and B levels were done for all the children. Among the children on highly active antiretroviral therapy (HAART), 38.3 % had dyslipidemia and 80.2 % had lipodystrophy, while 25 % antiretroviral therapy (ART) naïve HIV infected children had dyslipidemia. No clinically significant risk factors could be identified that increased the risk of dyslipidemia or lipodystrophy in children on highly active antiretroviral therapy (HAART). There is a high prevalence of dyslipidemia and lipodystrophy in Indian children with HIV infection with an imminent need to establish facilities for testing and treatment of these children for metabolic abnormalities.

Saroglitazar for the treatment of dyslipidemia in diabetic patients.

PubMed

Joshi, Shashank R

2015-03-01

Diabetes and dyslipidemia are commonly associated modifiable risk factors for cardiovascular diseases. Majority of patients with diabetes also suffer from dyslipidemia (diabetic dyslipidemia). Diabetic dyslipidemia is more atherogenic as it is commonly associated with high triglyceride (TG) levels, high proportion of small dense low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol (HDL-C) level (atherogenic dyslipidemia). Currently used pharmacotherapies for the management of diabetes and dyslipidemia like thiazolidinediones (PPAR-γ agonist; for insulin resistance) and fibrates (PPAR-α agonist; for hypertriglyceridemia) have many limitations and side effects. Saroglitazar , a dual PPAR-α/γ agonists, is an emerging therapeutic option with its dual benefit on glycemic and lipid parameters. This paper reviews the clinical development of saroglitazar for the management of diabetic dyslipidemia. The efficacy and safety profile of saroglitazar is reviewed in context to currently available therapy like pioglitazone for diabetes and fibrates for hypertriglyceridemia. In addition, this paper also reviews the association between diabetes and dyslipidemia and the role of TG in reducing cardiovascular events. Saroglitazar, a dual PPAR-α/γ agonist, is a potential therapeutic option for the management of diabetic dyslipidemia. It has dual benefit of significant improvement in glycemic parameters (glycated hemoglobin and fasting blood glucose) and significant improvement in dyslipidemia (TGs, apolipoprotein B, non-HDL-C). The results of Phase III clinical trials indicate that saroglitazar is devoid of conventional side effects of fibrates and pioglitazone. Future clinical trials of saroglitazar will further establish its place in the management of diabetes, dyslipidemia and associated cardiovascular risk.

Dyslipidemia and Auditory Function

PubMed Central

Evans, M. Bradley; Tonini, Ross; Shope, Cynthia Do; Oghalai, John S.; Jerger, James F.; Insull, William; Brownell, William E.

2013-01-01

The relationship between dyslipidemia and hearing is unclear. This study was conducted to investigate whether elevated serum lipid levels impact auditory function in humans and in guinea pigs. In the human study, a cross-sectional study of 40 volunteers with dyslipidemia was conducted. Pure tone thresholds, distortion product otoacoustic emissions, and lipid profiles were analyzed. When controlled for patient age and sex, we found that elevated triglycerides were associated with reduced hearing. In the guinea pig study, a prospective study of animals fed a high-fat diet for 14 weeks was conducted. Although the high-fat diet led to a dramatic elevation in the average weight and total cholesterol in all animals (from 61 to 589 mg/dl), there were no meaningful changes in distortion product otoacoustic emission magnitudes. These results suggest that whereas chronic dyslipidemia associated with elevated triglycerides may reduce auditory function, short-term dietary changes may not. PMID:16868509

Mixed dyslipidemias in primary care patients in France.

PubMed

Laforest, Laurent; Ambegaonkar, Baishali M; Souchet, Thierry; Sazonov, Vasilisa; Van Ganse, Eric

2012-01-01

To determine the prevalence of single and mixed dyslipidemias among patients treated with statins in clinical practice in France. This is a prospective, observational, cross-sectional, pharmacoepidemiologic study with a total of 2544 consecutive patients treated with a statin for at least 6 months. Prevalence of isolated and mixed dyslipidemias of low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides among all patients and among patients at high cardiovascular risk; clinical variables associated with attainment of lipid targets/normal levels in French national guidelines. At least one dyslipidemia was present in 50.8% of all patients and in 71.1% of high-risk patients. Dyslipidemias of LDL-C, HDL-C, and triglycerides were present in 27.7%, 12.4%, and 28.7% of all patients, respectively, and in 51.0%, 18.2%, and 32.5% of high-risk patients, respectively. Among all subjects with any dyslipidemia, 30.9% had mixed dyslipidemias and 69.4% had low HDL-C and/or elevated triglycerides, while 30.6% had isolated elevated LDL-C; corresponding values for high-risk patients were 36.8%, 58.9%, and 41.1%. Age, gender, body mass index and Framingham Risk Score >20% were the factors significantly associated with attainment of normal levels for ≥2 lipid levels. At least one dyslipidemia persisted in half of all patients and two-thirds of high cardiovascular risk patients treated with a statin. Dyslipidemias of HDL-C and/or triglycerides were as prevalent as elevated LDL-C among high cardiovascular risk patients.

Genetics of Dyslipidemia and Ischemic Heart Disease.

PubMed

Sharma, Kavita; Baliga, Ragavendra R

2017-05-01

Genetic dyslipidemias contribute to the prevalence of ischemic heart disease. The field of genetic dyslipidemias and their influence on atherosclerotic heart disease is rapidly developing and accumulating increasing evidence. The purpose of this review is to describe the current state of knowledge in regard to inherited atherogenic dyslipidemias. The disorders of familial hypercholesterolemia (FH) and elevated lipoprotein(a) will be detailed. Genetic technology has made rapid advancements, leading to new discoveries in inherited atherogenic dyslipidemias, which will be explored in this review, as well as a description of possible future developments. Increasing attention has come upon the genetic disorders of familial hypercholesterolemia and elevated lipoprotein(a). This review includes new knowledge of these disorders including description of these disorders, their method of diagnosis, their prevalence, their genetic underpinnings, and their effect on the development of cardiovascular disease. In addition, it discusses major advances in genetic technology, including the completion of the human genome sequence, next-generation sequencing, and genome-wide association studies. Also discussed are rare variant studies with specific genetic mechanisms involved in inherited dyslipidemias, such as in the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme. The field of genetics of dyslipidemia and cardiovascular disease is rapidly growing, which will result in a bright future of novel mechanisms of action and new therapeutics.

Mixed dyslipidemias in primary care patients in France

PubMed Central

Laforest, Laurent; Ambegaonkar, Baishali M; Souchet, Thierry; Sazonov, Vasilisa; Van Ganse, Eric

2012-01-01

Objective To determine the prevalence of single and mixed dyslipidemias among patients treated with statins in clinical practice in France. Methods This is a prospective, observational, cross-sectional, pharmacoepidemiologic study with a total of 2544 consecutive patients treated with a statin for at least 6 months. Main outcome measures Prevalence of isolated and mixed dyslipidemias of low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides among all patients and among patients at high cardiovascular risk; clinical variables associated with attainment of lipid targets/normal levels in French national guidelines. Results At least one dyslipidemia was present in 50.8% of all patients and in 71.1% of high-risk patients. Dyslipidemias of LDL-C, HDL-C, and triglycerides were present in 27.7%, 12.4%, and 28.7% of all patients, respectively, and in 51.0%, 18.2%, and 32.5% of high-risk patients, respectively. Among all subjects with any dyslipidemia, 30.9% had mixed dyslipidemias and 69.4% had low HDL-C and/or elevated triglycerides, while 30.6% had isolated elevated LDL-C; corresponding values for high-risk patients were 36.8%, 58.9%, and 41.1%. Age, gender, body mass index and Framingham Risk Score >20% were the factors significantly associated with attainment of normal levels for ≥2 lipid levels. Conclusions At least one dyslipidemia persisted in half of all patients and two-thirds of high cardiovascular risk patients treated with a statin. Dyslipidemias of HDL-C and/or triglycerides were as prevalent as elevated LDL-C among high cardiovascular risk patients. PMID:22566746

Increased serum soluble corin in dyslipidemia: A cross-sectional study.

PubMed

Wang, Xiaolei; Chen, Shi; Zhang, Qiu; Liu, Yan; Liu, Lu; Li, Huiling; Peng, Hao

2015-10-23

Natriuretic peptides have been associated with dyslipidemia. As a physiological activator of natriuretic peptides, corin might also be associated with dyslipidemia. However, this association has not yet been studied in Chinese populations. Serum soluble corin and blood lipid profiles were determined for 2496 participants aged above 30y. A logistic regression model was applied to evaluate the association between serum soluble corin and dyslipidemia. Serum soluble corin was significantly increased in participants with dyslipidemia in both men (P<0.001) and women (P<0.001). After controlling for the confounding factors, OR of dyslipidemia positively increased with increasing levels of serum soluble corin in men (P for trend=0.011) and women (P for trend=0.043). Participants with a high corin level were more likely to have dyslipidemia than those with a low corin level in men (OR, 95% CI: 1.45, 1.07-1.97) and women (OR, 95% CI: 1.33, 1.04-1.70). Serum soluble corin was significantly and positively associated with dyslipidemia. Our findings suggested that serum soluble corin may be a marker or risk factor for dyslipidemia. Copyright © 2015 Elsevier B.V. All rights reserved.

Circulating metabolomic profile can predict dyslipidemia in HIV patients undergoing antiretroviral therapy.

PubMed

Rodríguez-Gallego, Esther; Gómez, Josep; Domingo, Pere; Ferrando-Martínez, Sara; Peraire, Joaquim; Viladés, Consuelo; Veloso, Sergi; López-Dupla, Miguel; Beltrán-Debón, Raúl; Alba, Verónica; Vargas, Montserrat; Castellano, Alfonso J; Leal, Manuel; Pacheco, Yolanda María; Ruiz-Mateos, Ezequiel; Gutiérrez, Félix; Vidal, Francesc; Rull, Anna

2018-06-01

Dyslipidemia in HIV-infected patients is unique and pathophysiologically associated with host factors, HIV itself and the use of antiretroviral therapy (ART). The use of nuclear magnetic resonance spectroscopy (NMR) provides additional data to conventional lipid measurements concerning the number of lipoprotein subclasses and particle sizes. To investigate the ability of lipoprotein profile, we used a circulating metabolomic approach in a cohort of 103 ART-naive HIV-infected patients, who were initiating non-nucleoside analogue transcriptase inhibitor (NNRTI)-based ART, and we subsequently followed up these patients for 36 months. Univariate and multivariate analyses were performed to evaluate the predictive power of NMR spectroscopy. VLDL-metabolism (including VLDL lipid concentrations, sizes, and particle numbers), total triglycerides and lactate levels resulted in good classifiers of dyslipidemia (AUC 0.903). Total particles/HDL-P ratio was significantly higher in ART-associated dyslipidemia compared to ART-normolipidemia (p = 0.001). Large VLDL-Ps were positively associated with both LDL-triglycerides (ρ 0.682, p < 0.001) and lactate concentrations (ρ 0.416, p < 0.001), the last one a marker of mitochondrial low oxidative capacity. Our data suggest that circulating metabolites have better predictive values for HIV/ART-related dyslipidemia onset than do the biochemical markers associated with conventional lipid measurements. NMR identifies changes in VLDL-P, lactate and LDL-TG as potential clinical markers of baseline HIV-dyslipidemia predisposition. Differences in circulating metabolomics, especially differences in particle size, are indicators of important derangements of mitochondrial function that are linked to ART-related dyslipidemia. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Dyslipidemia in systemic lupus erythematosus: just another comorbidity?

PubMed

Tselios, Konstantinos; Koumaras, Charalambos; Gladman, Dafna D; Urowitz, Murray B

2016-04-01

Among traditional atherosclerotic risk factors, dyslipidemia is believed to decisively affect the long-term prognosis of lupus patients, not only with regard to cardiovascular events but also by influencing other manifestations, such as lupus nephritis. The aim of this study was to review the epidemiology, pathogenesis, evidence for its impact on atherosclerosis manifestations and management of dyslipidemia in lupus patients. English-restricted MEDLINE database search (Medical Subject Headings: lupus or systemic lupus erythematosus and dyslipidemia or hyperlipidemia). The prevalence of dyslipidemia in systemic lupus erythematosus (SLE) ranges from 36% at diagnosis to 60% or even higher after 3 years, depending on definition. Multiple pathogenetic mechanisms are implicated, including antibodies against lipoprotein lipase and cytokines affecting the balance between pro- and anti-atherogenic lipoproteins. Dyslipidemia has a clear impact on clinical cardiovascular disease and surrogate markers for subclinical atherosclerosis. Moreover, it negatively affects end-organ damage (kidneys and brain). Treatment with statins yielded contradictory results as per minimizing cardiovascular risk. Dyslipidemia is a significant comorbidity of lupus patients with multiple negative effects in the long term. Its treatment represents a modifiable risk factor; prompt and adequate treatment can minimize unnecessary burden in lupus patients, thus reducing hospitalizations and their overall morbidity and mortality. Copyright © 2016 Elsevier Inc. All rights reserved.

Drug-related problems in type 2 diabetes mellitus patients with dyslipidemia

PubMed Central

2013-01-01

Background Drug-Related Problems (DRPs) commonly occur among type 2 diabetes mellitus (T2DM) patients. However, few studies have been performed on T2DM patients with dyslipidemia. This purpose of this study was to assess drug-related problems (DRPs) and factors associated with its occurrence. Methods The retrospective study involved 208 T2DM in-patients and out-patients with dyslipidemia, and was conducted at a tertiary hospital in Malaysia from January 2009 to December 2011. The identification and assessment of DRPs were based on the Pharmaceutical Care Network Europe (PCNE) tool version 5.01. The potentially inappropriate medication use in older adults was assessed based on the American Geriatrics Society updated Beers Criteria. Results A total of 406 DRPs were identified. Among these patients, 91.8% had at least one DRP, averaging 1.94 ± 1.10 problems per patient. The majority of T2DM patients with dyslipidemia (91.8%) had at least one DRP. The most frequent types of DRP were potential drug-drug interaction (18.0%), drug not taken or administered (14.3%) and insufficient awareness of health and diseases (11.8%). Anti-hypertensive, lipid-modifying and anti-diabetic agents were the drug classes that were most likely to be associated with DRPs. Male gender, renal impairment, polypharmacy and poor lipid control were factors that were significantly associated with DRP in diabetic dyslipidemia patients. Conclusion Early identification of DRPs and factors associated with them are essential to prevent and resolve DRPs in T2DM patients with dyslipidemia. PMID:24341672

Polygenic influences on dyslipidemias.

PubMed

Dron, Jacqueline S; Hegele, Robert A

2018-04-01

Rare large-effect genetic variants underlie monogenic dyslipidemias, whereas common small-effect genetic variants - single nucleotide polymorphisms (SNPs) - have modest influences on lipid traits. Over the past decade, these small-effect SNPs have been shown to cumulatively exert consistent effects on lipid phenotypes under a polygenic framework, which is the focus of this review. Several groups have reported polygenic risk scores assembled from lipid-associated SNPs, and have applied them to their respective phenotypes. For lipid traits in the normal population distribution, polygenic effects quantified by a score that integrates several common polymorphisms account for about 20-30% of genetic variation. Among individuals at the extremes of the distribution, that is, those with clinical dyslipidemia, the polygenic component includes both rare variants with large effects and common polymorphisms: depending on the trait, 20-50% of susceptibility can be accounted for by this assortment of genetic variants. Accounting for polygenic effects increases the numbers of dyslipidemic individuals who can be explained genetically, but a substantial proportion of susceptibility remains unexplained. Whether documenting the polygenic basis of dyslipidemia will affect outcomes in clinical trials or prospective observational studies remains to be determined.

[Associations of sedentary behavior and physical activity with dyslipidemia].

PubMed

Zhou, J; Zhou, Q; Wang, D P; Zhang, T; Wang, H J; Song, Y; He, H Z; Wang, M; Wang, P Y; Liu, A P

2017-06-18

To analyze associations of sedentary behavior and physical activity with dyslipidemia among residents in Wuhai city. Data about social demographic characteristics, life style, health status and other covariate required for analysis in this study was obtained from a cross-sectional study on a total of 11 497 18-79 years old residents in Wuhai City by questionnaire, body mea-surement and laboratory examination. In this study, sedentary behavior and physical activity were evaluated using international physical activity questionnaire long version (IPAQ). IPAQ is widely used all over the world, and its reliability and validity have been tested in Chinese population. 2016 Chinese Guideline for the Management of Dyslipidemia in Adults was used to define dyslipidemia in this study. According to IPAQ scoring protocol, 124 participants were excluded as a result of reporting more than 960 min of physical activity per day. 50.58% of 11 373 participants included in the analysis reported more than 4 hours of sedentary behavior per day in this study, thus 49.42% participants reported no more than 4 hours of sedentary behavior per day; the proportions of these 11 373 participants who reached Low level physical activity, Moderate level physical activity and high level physical activity were 23.43%, 37.29% and 39.28% respectively; and the detection ratios of new cases and prevalent cases of dyslipidemia in Wuhai City were 20.46% and 16.13% respectively. After controlling for confounders in this study, we found out that sedentary behavior increased the risk of new cases of dyslipidemia in women (OR=1.17, 95% CI: 1.00-1.36), and increased the risk of prevalent cases of dyslipidemia in both men (OR=1.21, 95% CI: 1.02-1.44) and women (OR=1.24, 95% CI: 1.04-1.48); as for association of physical activity with dyslipidemia, association was found between high level physical activity and prevalent cases of dyslipidemia in men in this study (OR=0.78, 95% CI: 0.62-0.98), suggested that high

Prevalence and Risk Factors Associated with Dyslipidemia in Chongqing, China.

PubMed

Qi, Li; Ding, Xianbin; Tang, Wenge; Li, Qin; Mao, Deqiang; Wang, Yulin

2015-10-26

The increasing prevalence of dyslipidemia has become a worldwide public health problem, and the prevalence varies widely according to socioeconomic, cultural and ethnic characteristics. Chongqing has experienced rapid economic development and is now the economic center of Southwestern China. There are scant data on serum lipid profile of residents in Chongqing, the largest municipality directly under the Central Government in China. We conducted a cross-sectional study in a representative sample of 5375 residents of Chongqing, aged ≥18 years, and estimated the prevalence of dyslipidemia and its associated risk factors. According to the National Cholesterol Education Program-Adult Treatment Panel III criteria, the age-standardized prevalence of dyslipidemia was 35.5% (34.4% among men and 37.6% among women). Among the 2009 patients with dyslipidemia, 44.2% had isolated hypertriglyceridemia, 14.7% had isolated hypercholesterolemia, 13.2% had mixed hyperlipidemia, and 28.0% had isolated low high-density lipoprotein cholesterol. The peak prevalence of dyslipidemia in men was between 30 and 39 years (48.2%), and then declined gradually; in women, the prevalence of dyslipidemia increased with age, with the peak prevalence occurring after age 60 (46.3%). Multivariable logistic regression analysis revealed that dyslipidemia was associated with age, education level, physical activity, obesity and central obesity for both men and women. In conclusion, the results indicated dyslipidemia, particularly hypertriglyceridemia and low high-density lipoprotein cholesterol, are very common in Chongqing. To prevent dyslipidemia, it is essential to conduct appropriate intervention programs aimed at risk factor reduction and implement routine screening programs for blood lipid levels in Chongqing, China.

Prevalence and Risk Factors Associated with Dyslipidemia in Chongqing, China

PubMed Central

Qi, Li; Ding, Xianbin; Tang, Wenge; Li, Qin; Mao, Deqiang; Wang, Yulin

2015-01-01

The increasing prevalence of dyslipidemia has become a worldwide public health problem, and the prevalence varies widely according to socioeconomic, cultural and ethnic characteristics. Chongqing has experienced rapid economic development and is now the economic center of Southwestern China. There are scant data on serum lipid profile of residents in Chongqing, the largest municipality directly under the Central Government in China. We conducted a cross-sectional study in a representative sample of 5375 residents of Chongqing, aged ≥18 years, and estimated the prevalence of dyslipidemia and its associated risk factors. According to the National Cholesterol Education Program-Adult Treatment Panel III criteria, the age-standardized prevalence of dyslipidemia was 35.5% (34.4% among men and 37.6% among women). Among the 2009 patients with dyslipidemia, 44.2% had isolated hypertriglyceridemia, 14.7% had isolated hypercholesterolemia, 13.2% had mixed hyperlipidemia, and 28.0% had isolated low high-density lipoprotein cholesterol. The peak prevalence of dyslipidemia in men was between 30 and 39 years (48.2%), and then declined gradually; in women, the prevalence of dyslipidemia increased with age, with the peak prevalence occurring after age 60 (46.3%). Multivariable logistic regression analysis revealed that dyslipidemia was associated with age, education level, physical activity, obesity and central obesity for both men and women. In conclusion, the results indicated dyslipidemia, particularly hypertriglyceridemia and low high-density lipoprotein cholesterol, are very common in Chongqing. To prevent dyslipidemia, it is essential to conduct appropriate intervention programs aimed at risk factor reduction and implement routine screening programs for blood lipid levels in Chongqing, China. PMID:26516874

Management Status of Cardiovascular Disease Risk Factors for Dyslipidemia among Korean Adults.

PubMed

Lee, Jongseok; Son, Heejeong; Ryu, Ohk Hyun

2017-03-01

Dyslipidemia, hypertension, and diabetes are well-established risk factors for cardiovascular disease (CVD). This study investigated the prevalence and management status of these factors for dyslipidemia among Korean adults aged 30 years old and older. The prevalence and management status of dyslipidemia, hypertension, and diabetes were analyzed among 12229 subjects (≥30 years) participating in the Korea National Health and Nutrition Survey 2010-2012. Dyslipidemia was defined according to treatment criteria rather than diagnostic criteria in Korea. Therefore, hyper-low-density lipoprotein (LDL) cholesterolemia was defined if LDL cholesterol levels exceeded the appropriate risk-based threshold established by the National Cholesterol Education Program Adult Treatment Panel III. The age-standardized prevalence was highest for dyslipidemia (39.6%), followed by hypertension (32.8%) and diabetes (9.8%). The lowest patient awareness was found for dyslipidemia (27.9%). The treatment rate was 66.5% for diabetes and 57.3% for hypertension, but only 15.7% for dyslipidemia. The control rate among those undergoing treatment was highest for hypertension (64.2%), followed by dyslipidemia (59.2%) and diabetes (22.1%). The higher the risk levels of CVD were, the lower the control rate of dyslipidemia. While the prevalence of dyslipidemia was higher than hypertension and diabetes, awareness and treatment rates thereof were lower. Higher CVD-risk categories showed lower control rates of dyslipidemia. In order to improve awareness and control rates of dyslipidemia, diagnostic criteria should be reconciled with treatment targets based on cardiovascular risk in Korean populations.

[High frequency of dyslipidemia in children and adolescents with Down Syndrome].

PubMed

de la Piedra, María J; Alberti, Gigliola; Cerda, Jaime; Cárdenas, Antonia; Paul, María A; Lizama, Macarena

2017-01-01

Down Syndrome (DS) shows an increased risk of chronic diseases, associated to higher morbidity and mortality for cardiovascular disease. Some studies have shown a worse lipid profile in children with DS, however, until now there is no recommendation for screening for dyslipidemia in these subjects. To describe the frequency of dyslipidemia in a population of Chilean children and adolescents with DS. Retrospective study, including patients with DS, aged 2 to 18 years, who participated in a special health care program for people with DS in Health Net UC CHRISTUS, between 2007 and 2015. Patients who had a lipid profile between their routine laboratory tests were included. Clinical characteristics, relevant comorbidities, malformations, medications, nutritional status and pubertal development were obtained from medical records. Diagnosis of dyslipidemia was considered according to the criteria of the NHLBI 2011. The medical records of 218 children with DS were revised, 58,3% had some type of dyslipidemia. The most frequent single dyslipidemias were low HDL Chol (15,1%) and hypertriglyceridemia (12,8%). Atherogenic dyslipidemia (low HDL plus hypertriglyceridemia) was the most frequent combined dyslipidemia (13,3%). The occurrence of atherogenic dyslipidemia was not associated with overnutrition and obesity. A high frequency of dyslipidemia was found in Chilean children and adolescents with DS. Our results make us suggest that lipid profile should be performed early in all patients with DS, independent of the presence of risk factors for dyslipidemia.

Atherogenic dyslipidemia: prevalence and management in lipid clinics.

PubMed

Pedro-Botet, J; Flores-Le Roux, J A; Mostaza, J M; Pintó, X; de la Cruz, J J; Banegas, J R

2014-12-01

Atherogenic dyslipidemia, which is characterized by increased triglyceride levels and reduced HDL cholesterol levels, is underestimated and undertreated in clinical practice. We assessed its prevalence and the achievement of therapeutic objectives for HDL cholesterol and triglyceride levels in patients treated at lipid and vascular risk units in Spain. This was an observational, longitudinal, retrospective, multicenter study performed in 14 autonomous Spanish communities that consecutively included 1828 patients aged ≥18 years who were referred for dyslipidemia and vascular risk to 43 lipid clinics accredited by the Spanish Society of Arteriosclerosis. We collected information from the medical records corresponding to 2 visits conducted during 2010 and 2011-12, respectively. Of the 1649 patients who had a lipid profile in the first visit (90.2%), 295 (17.9%) had atherogenic dyslipidemia. The factors associated with atherogenic dyslipidemia were excess weight/obesity, not taking hypolipidemic drugs (statins and/or fibrates), diabetes, myocardial infarction and previous heart failure. Of the 273 (92.5%) patients with atherogenic dyslipidemia that had a lipid profile in the last visit, 44 (16.1%) achieved the therapeutic objectives for HDL cholesterol and triglyceride levels. The predictors of therapeutic success were normal weight and normoglycemia. One of every 6 patients treated in lipid and vascular risk units had atherogenic dyslipidemia. The degree to which the therapeutic goals for HDL cholesterol and triglyceride levels were achieved in these patients was very low. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Dyslipidemia: Obese or Not Obese-That Is Not the Question.

PubMed

Ipsen, David H; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

2016-12-01

Purpose of review: It is becoming increasingly clear that some obese individuals do not develop dyslipidemia and instead remain healthy, while some normal weight individuals become dyslipidemic and unhealthy. The present review examines the similarities and differences between healthy and unhealthy individuals with and without obesity and discusses putative underlying mechanisms of dyslipidemia. The presence of dyslipidemia and compromised metabolic health in both lean and obese individuals suggests that the obese phenotype per se does not represent a main independent risk factor for the development of dyslipidemia and that dyslipidemia, rather than obesity, may be the driver of metabolic diseases. Notably, adipose tissue dysfunction and ectopic lipid deposition, in particular in the liver, seems a common trait of unhealthy individuals.

Management Status of Cardiovascular Disease Risk Factors for Dyslipidemia among Korean Adults

PubMed Central

Lee, Jongseok

2017-01-01

Purpose Dyslipidemia, hypertension, and diabetes are well-established risk factors for cardiovascular disease (CVD). This study investigated the prevalence and management status of these factors for dyslipidemia among Korean adults aged 30 years old and older. Materials and Methods The prevalence and management status of dyslipidemia, hypertension, and diabetes were analyzed among 12229 subjects (≥30 years) participating in the Korea National Health and Nutrition Survey 2010–2012. Dyslipidemia was defined according to treatment criteria rather than diagnostic criteria in Korea. Therefore, hyper-low-density lipoprotein (LDL) cholesterolemia was defined if LDL cholesterol levels exceeded the appropriate risk-based threshold established by the National Cholesterol Education Program Adult Treatment Panel III. Results The age-standardized prevalence was highest for dyslipidemia (39.6%), followed by hypertension (32.8%) and diabetes (9.8%). The lowest patient awareness was found for dyslipidemia (27.9%). The treatment rate was 66.5% for diabetes and 57.3% for hypertension, but only 15.7% for dyslipidemia. The control rate among those undergoing treatment was highest for hypertension (64.2%), followed by dyslipidemia (59.2%) and diabetes (22.1%). The higher the risk levels of CVD were, the lower the control rate of dyslipidemia. Conclusion While the prevalence of dyslipidemia was higher than hypertension and diabetes, awareness and treatment rates thereof were lower. Higher CVD-risk categories showed lower control rates of dyslipidemia. In order to improve awareness and control rates of dyslipidemia, diagnostic criteria should be reconciled with treatment targets based on cardiovascular risk in Korean populations. PMID:28120563

Prevalence and pattern of dyslipidemia in Nepalese individuals with type 2 diabetes.

PubMed

Pokharel, Daya Ram; Khadka, Dipendra; Sigdel, Manoj; Yadav, Naval Kishor; Acharya, Shreedhar; Kafle, Ramchandra; Sapkota, Ravindra Mohan; Sigdel, Tara

2017-04-04

Atherogenic dyslipidemia is an important modifiable risk factor for cardiovascular disease among patients of type 2 diabetes mellitus. Timely detection and characterization of this condition help clinicians estimate future risk of cardiovascular disease and take appropriate preventive measures. The aim of this study was to determine the prevalence, pattern and predictors of dyslipidemia in a cohort of Nepalese patients with type 2 diabetes. We found mixed dyslipidemia as the most prevalent (88.1%) and isolated dyslipidemia (10.1%) as the least prevalent forms of dyslipidemia in our patients. The most prevalent form of single dyslipidemia was high LDL-C (73.8%) and combined dyslipidemia was high TG, high LDL-C and low HDL-C (44.7%). Prevalence of all single and mixed dyslipidemia was higher in patients with poor glycemic control and hypertension. The glycemic status of patients correlated with their fasting serum lipid profile. Dyslipidemia was associated mainly with male gender, poor glycemic control and hypertension. Atherogenic dyslipidemia is associated mainly with male gender, poor glycemic control and hypertension. It is highly prevalent in Nepalese patients with type 2 diabetes. Urgent lifestyle modification, sustained glycemic control and aggressive lipid lowering treatment plans are necessary to minimize the future risk of cardiovascular disease in this population.

Dyslipidemia: management using optimal lipid-lowering therapy.

PubMed

Ito, Matthew K

2012-10-01

To evaluate current approaches and explore emerging research related to dyslipidemia management. MEDLINE (2004-April 2012) was searched for randomized controlled trials using the terms dyslipidemia and lipid-lowering therapy or statin (>1000 hits). Separate searches (MEDLINE, Google) identified meta-analyses (2010-2011), disease prevalence statistics, and current consensus guidelines (2004-July 2011). Additional references were identified from the publications reviewed. English-language articles on large multicenter trials were evaluated. National Cholesterol Education Program Adult Treatment Panel III guidelines for the reduction of cardiovascular risk recommend the attainment of specific low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) target values, based on an individual's 10-year risk of coronary heart disease or global risk. For most patients unable to achieve recommended lipid level goals with therapeutic lifestyle changes, statins are the first option for treatment. Results of large, well-controlled clinical trials have demonstrated that statins are effective in primary and secondary prevention of cardiovascular disease in diverse populations, including patients with diabetes and the elderly, and that intensive statin therapy provides more effective lipid goal attainment and significantly greater risk reduction in patients with coronary artery disease. Statin therapy is generally well tolerated but may increase the risk of myopathy. Statin use has been associated with increases in hepatic transaminases and an increased risk of diabetes, although the absolute risk of diabetes is low compared with the risk reduction benefit. Combination therapy including a statin may be appropriate for certain populations, but the risk reduction benefits of combination therapy remain unclear. Ezetimibe is an important treatment option for patients with hypercholesterolemia who do not tolerate intensive statin therapy

Cadmium Exposure is Associated with the Prevalence of Dyslipidemia.

PubMed

Zhou, Zhou; Lu, Yong-Hui; Pi, Hui-Feng; Gao, Peng; Li, Min; Zhang, Lei; Pei, Li-Ping; Mei, Xiang; Liu, Lin; Zhao, Qi; Qin, Qi-Zhong; Chen, Yu; Jiang, Yue-Ming; Zhang, Zhao-Hui; Yu, Zheng-Ping

2016-01-01

Cadmium is a widespread environmental and occupational pollutant that accumulates in human body with a biological half-life exceeding 10 years. Cadmium exposure has been demonstrated to increase rates of cardiovascular diseases. Whether occupational cadmium exposure is associated with the increase in the prevalence of dyslipidemia and hence contributes to the risk of cardiovascular diseases is still equivocal. To test the hypothesis that exposure to cadmium is related to the prevalence of dyslipidemia, we examined the associations between blood cadmium concentration and the prevalence of dyslipidemia in workers occupationally exposed to cadmium in China. A cross-sectional survey on demographic data, blood cadmium level and lipid profile in cadmium exposed workers from seven cadmium smelting factories in central and southwestern China was conducted. We measured blood cadmium concentration and lipid components of 1489 cadmium exposed workers. The prevalence of dyslipidemia was compared across blood cadmium quartiles. Associations between the blood cadmium concentrations and the prevalence of dyslipidemia were assessed using confounder adjusted linear and logistic regressions. The blood cadmium concentration was 3.61±0.84µg/L ( mean ±SD). The prevalence of dyslipidemia in this occupational population was 66.3%. Mean blood cadmium concentration of workers with dyslipedemia was significantly higher than that of workers without dyslipidemia (p <0.01). The prevalence of dyslipidemia increased dose-dependently with elevations in blood cadmium concentrations (p for trend <0.001). Elevated levels of blood cadmium were associated with BMI, education attainment, income, smoking status and duration of exposure (all p <0.01). Furthermore, the profile of blood lipid was obviously changed in this occupational population. The prevalence of high TC, high TG, Low HDL-C and high LDL-C rose with increases in blood cadmium levels dose-dependently (p for trend <0.001). The odds ratios

Genome-wide association study identifies HLA 8.1 ancestral haplotype alleles as major genetic risk factors for myositis phenotypes.

PubMed

Miller, F W; Chen, W; O'Hanlon, T P; Cooper, R G; Vencovsky, J; Rider, L G; Danko, K; Wedderburn, L R; Lundberg, I E; Pachman, L M; Reed, A M; Ytterberg, S R; Padyukov, L; Selva-O'Callaghan, A; Radstake, T R; Isenberg, D A; Chinoy, H; Ollier, W E R; Scheet, P; Peng, B; Lee, A; Byun, J; Lamb, J A; Gregersen, P K; Amos, C I

2015-10-01

Autoimmune muscle diseases (myositis) comprise a group of complex phenotypes influenced by genetic and environmental factors. To identify genetic risk factors in patients of European ancestry, we conducted a genome-wide association study (GWAS) of the major myositis phenotypes in a total of 1710 cases, which included 705 adult dermatomyositis, 473 juvenile dermatomyositis, 532 polymyositis and 202 adult dermatomyositis, juvenile dermatomyositis or polymyositis patients with anti-histidyl-tRNA synthetase (anti-Jo-1) autoantibodies, and compared them with 4724 controls. Single-nucleotide polymorphisms showing strong associations (P<5×10(-8)) in GWAS were identified in the major histocompatibility complex (MHC) region for all myositis phenotypes together, as well as for the four clinical and autoantibody phenotypes studied separately. Imputation and regression analyses found that alleles comprising the human leukocyte antigen (HLA) 8.1 ancestral haplotype (AH8.1) defined essentially all the genetic risk in the phenotypes studied. Although the HLA DRB1*03:01 allele showed slightly stronger associations with adult and juvenile dermatomyositis, and HLA B*08:01 with polymyositis and anti-Jo-1 autoantibody-positive myositis, multiple alleles of AH8.1 were required for the full risk effects. Our findings establish that alleles of the AH8.1 comprise the primary genetic risk factors associated with the major myositis phenotypes in geographically diverse Caucasian populations.

Genome-wide Association Study Identifies HLA 8.1 Ancestral Haplotype Alleles as Major Genetic Risk Factors for Myositis Phenotypes

PubMed Central

Miller, Frederick W.; Chen, Wei; O’Hanlon, Terrance P.; Cooper, Robert G.; Vencovsky, Jiri; Rider, Lisa G.; Danko, Katalin; Wedderburn, Lucy R.; Lundberg, Ingrid E.; Pachman, Lauren M.; Reed, Ann M.; Ytterberg, Steven R.; Padyukov, Leonid; Selva-O’Callaghan, Albert; Radstake, Timothy R.; Isenberg, David A.; Chinoy, Hector; Ollier, William E.R.; Scheet, Paul; Peng, Bo; Lee, Annette; Byun, Jinyoung; Lamb, Janine A.; Gregersen, Peter K.; Amos, Christopher I.

2016-01-01

Autoimmune muscle diseases (myositis) comprise a group of complex phenotypes influenced by genetic and environmental factors. To identify genetic risk factors in patients of European ancestry, we conducted a genome-wide association study (GWAS) of the major myositis phenotypes in a total of 1710 cases, which included 705 adult dermatomyositis; 473 juvenile dermatomyositis; 532 polymyositis; and 202 adult dermatomyositis, juvenile dermatomyositis or polymyositis patients with anti-histidyl tRNA synthetase (anti-Jo-1) autoantibodies, and compared them with 4724 controls. Single-nucleotide polymorphisms showing strong associations (P < 5 × 10−8) in GWAS were identified in the major histocompatibility complex (MHC) region for all myositis phenotypes together, as well as for the four clinical and autoantibody phenotypes studied separately. Imputation and regression analyses found that alleles comprising the human leukocyte antigen (HLA) 8.1 ancestral haplotype (AH8.1) defined essentially all the genetic risk in the phenotypes studied. Although the HLA DRB1*03:01 allele showed slightly stronger associations with adult and juvenile dermatomyositis, and HLA B*08:01 with polymyositis and anti-Jo-1 autoantibody-positive myositis, multiple alleles of AH8.1 were required for the full risk effects. Our findings establish that alleles of the AH8.1haplotype comprise the primary genetic risk factors associated with the major myositis phenotypes in geographically diverse Caucasian populations. PMID:26291516

[Diabetes and dyslipidemia: Why are they so closely related?

PubMed

Rašlová, Katarína

Diabetes mellitus is a group of metabolic diseases that are characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The cause of premature death among patients with diabetes predominantly involves cardiovascular diseases. The risk of death from cardiovascular complications is so high that diabetes mellitus is considered a risk equivalent to a manifest atherosclerotic disease. High cardiovascular risk is also determined by dyslipidemia which is present in a large number of patients with diabetes. The review is devoted to the pathogenesis of dyslipidemia in type 1 and type 2 diabetes with an emphasis on atherogenic dyslipidemia. It describes the strategy of therapeutic procedures and their effect on cardiovascular morbidity and mortality.Key words: atherogenic dyslipidemia - fibrates - statins - type 2 diabetes mellitus.

Identifying allelic loss and homozygous deletions in pancreatic cancer without matched normals using high-density single-nucleotide polymorphism arrays.

PubMed

Calhoun, Eric S; Hucl, Tomas; Gallmeier, Eike; West, Kristen M; Arking, Dan E; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Chakravarti, Aravinda; Hruban, Ralph H; Kern, Scott E

2006-08-15

Recent advances in oligonucleotide arrays and whole-genome complexity reduction data analysis now permit the evaluation of tens of thousands of single-nucleotide polymorphisms simultaneously for a genome-wide analysis of allelic status. Using these arrays, we created high-resolution allelotype maps of 26 pancreatic cancer cell lines. The areas of heterozygosity implicitly served to reveal regions of allelic loss. The array-derived maps were verified by a panel of 317 microsatellite markers used in a subset of seven samples, showing a 97.1% concordance between heterozygous calls. Three matched tumor/normal pairs were used to estimate the false-negative and potential false-positive rates for identifying loss of heterozygosity: 3.6 regions (average minimal region of loss, 720,228 bp) and 2.3 regions (average heterozygous gap distance, 4,434,994 bp) per genome, respectively. Genomic fractional allelic loss calculations showed that cumulative levels of allelic loss ranged widely from 17.1% to 79.9% of the haploid genome length. Regional increases in "NoCall" frequencies combined with copy number loss estimates were used to identify 41 homozygous deletions (19 first reports), implicating an additional 13 regions disrupted in pancreatic cancer. Unexpectedly, 23 of these occurred in just two lines (BxPc3 and MiaPaCa2), suggesting the existence of at least two subclasses of chromosomal instability (CIN) patterns, distinguished here by allelic loss and copy number changes (original CIN) and those also highly enriched in the genomic "holes" of homozygous deletions (holey CIN). This study provides previously unavailable high-resolution allelotype and deletion breakpoint maps in widely shared pancreatic cancer cell lines and effectively eliminates the need for matched normal tissue to define informative loci.

An artificial neural network system to identify alleles in reference electropherograms.

PubMed

Taylor, Duncan; Harrison, Ash; Powers, David

2017-09-01

Electropherograms are produced in great numbers in forensic DNA laboratories as part of everyday criminal casework. Before the results of these electropherograms can be used they must be scrutinised by analysts to determine what the identified data tells them about the underlying DNA sequences and what is purely an artefact of the DNA profiling process. This process of interpreting the electropherograms can be time consuming and is prone to subjective differences between analysts. Recently it was demonstrated that artificial neural networks could be used to classify information within an electropherogram as allelic (i.e. representative of a DNA fragment present in the DNA extract) or as one of several different categories of artefactual fluorescence that arise as a result of generating an electropherogram. We extend that work here to demonstrate a series of algorithms and artificial neural networks that can be used to identify peaks on an electropherogram and classify them. We demonstrate the functioning of the system on several profiles and compare the results to a leading commercial DNA profile reading system. Copyright © 2017 Elsevier B.V. All rights reserved.

Treatment of dyslipidemia in HIV-infected patients.

PubMed

Sekhar, Rajagopal V; Balasubramanyam, Ashok

2010-08-01

Patients infected with HIV are at high risk for dyslipidemia, insulin resistance and cardiovascular disease. Therapies to reverse these risks are complex, sometimes controversial, and not uniformly effective. Pathophysiology of the lipid abnormalities in HIV is discussed, including the causes of alterations in triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and insulin resistance. We discuss the therapy of dyslipidemia in HIV using a combination of available clinical evidence and expert opinion based on extensive clinical experience, with discussions of lifestyle intervention and diet, conventional pharmacotherapy with lipid-lowering medications including statins, fibrates, niacin and thiazolidinediones for dyslipidemia, and newer therapeutic approaches including omega fatty acids, acipimox, growth hormone and leptin. A detailed understanding of the pathophysiology and rational or evidence-based approach to therapy of lipid abnormalities in patients infected with HIV. Treatment of dyslipidemia in patients with HIV is challenging and complicated by the risk of drug interactions. Appropriate therapy requires a sound understanding of pathophysiology and the principles of pharmacological and nonpharmacological therapeutic interventions. An evidence-based approach that combines lifestyle changes and drugs that are both safe and effective, singly and in combination, is described.

Toenail mercury and dyslipidemia: Interaction with selenium.

PubMed

Park, Kyong; Seo, Eunmin

2017-01-01

Although compelling evidences from in vivo and in vitro studies exist, limited studies have examined the association between chronic mercury exposure and dyslipidemia. Particularly, data are sparse regarding the influence of selenium on this association of mercury with dyslipidemia in humans. The purpose of the current study was to examine the associations of toenail mercury with dyslipidemia and its components, and to examine whether selenium in toenails modifies these associations. We performed cross-sectional analyses using baseline data from a cohort in the Yeungnam area in South Korea, including 232 men and 269 women. Toenail mercury and selenium concentrations were quantified using neutron activation analysis, and fasting serum lipid measurements were obtained through the medical examination. Odds ratios of the prevalent hypercholesterolemia, hyper-LDL-cholesterolemia, hypo-HDL-cholesterolemia, hypertriglyceridemia, and dyslipidemia in correlation with mercury levels were calculated using multivariable logistic regression. The mean levels of toenail mercury were 0.47μg/g for men and 0.34μg/g for women. After adjustment for multiple confounding variables, participants in the highest tertile of toenail mercury levels had 4.08 (95% CI 1.09-15.32, p for trend=0.02) times higher risk of hyper-LDL-cholesterolemia, and 2.24 (95% CI 1.15-4.37, p for trend=0.004) times higher risk of dyslipidemia than those in the lowest tertile. Selenium is a significant effect-modifier for these associations; the highest tertile of toenail mercury were significantly associated with a higher risk of hypercholesterolemia (OR 5.25, 95% CI 1.04-26.38) and dyslipidemia (OR 2.98, 95% CI 1.16-7.66) compared to the lowest tertile at toenail selenium levels ≤0.685μg/g, while these associations became weak and non-significant, showing OR 0.98 and 95% CI 0.25-3.80 for hypercholesterolemia and OR 1.99 and 95% CI 0.73-5.45 for dyslipidemia at toenail selenium levels >0.685μg/g. We

Prevalence of Dyslipidemia Among Antiretroviral-Naive HIV-Infected Individuals in China

PubMed Central

Shen, Yinzhong; Wang, Jiangrong; Wang, Zhenyan; Qi, Tangkai; Song, Wei; Tang, Yang; Liu, Li; Zhang, Renfang; Lu, Hongzhou

2015-01-01

Abstract Little is known about the epidemiological features of dyslipidemia among antiretroviral-naive HIV-infected individuals in China. We used a cross-sectional study design to estimate the prevalence of dyslipidemia in this population, and to identify risk factors associated with the presence of dyslipidemia. One thousand five hundred and eighteen antiretroviral-naive HIV-infected individuals and 347 HIV-negative subjects in China were enrolled during 2009 to 2010. Demographics and medical histories were recorded. After an overnight fast, serum samples were collected to measure lipid levels. Factors associated with the presence of dyslipidemia were analyzed by logistic regression. Mean total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL) levels were lower in HIV-positive than HIV-negative subjects, but mean triglyceride (TG) was higher in HIV-positive subjects. The overall prevalence of dyslipidemia in HIV-positive and HIV-negative groups did not differ (75.6% vs. 73.7%, P = 0.580). However, the prevalence of high TC (8.4% vs. 28.2%, P < 0.001) and high LDL (8.5% vs. 62.6%, P < 0.001) was lower in HIV-positive than HIV-negative subjects, and the prevalence of high TG (33.9% vs. 17.0%, P < 0.001) and low HDL (59.6% vs. 11.2%, P < 0.001) was higher in HIV-positive than HIV-negative subjects. Logistic analysis showed that HIV positivity was significantly associated with both an increased risk of high TG and low HDL and a decreased risk of high TC and high LDL. The mean levels of TC, of LDL and of HDL showed an increasing trend with increasing CD4 count in HIV-positive subjects. Multivariable logistic regression found that lower CD4 count was significantly associated with both an increased risk of high TG and low HDL and a decreased risk of high TC in HIV-positive subjects. Among antiretroviral-naive HIV-infected Chinese adults, there was a high prevalence of dyslipidemia characterized by

The new dyslipidemia guidelines: what is the debate?

PubMed

Anderson, Todd J; Mancini, G B John; Genest, Jacques; Grégoire, Jean; Lonn, Eva M; Hegele, Robert A

2015-05-01

Dyslipidemia is a major risk factor for the development of atherosclerotic disease. Therefore, lifestyle interventions and pharmacological approaches to decrease cholesterol are widely used in cardiovascular disease prevention. The introduction and widespread use of 3-hydroxy-3 methylglutaryl coenzyme A inhibitors (statins) for individuals at risk of atherosclerotic disease has been an important advance in cardiovascular care. There can be no doubt that better control of dyslipidemia, even in subjects whose low-density lipoprotein cholesterol level is not particularly high, has reduced overall event rates. On a background of lifestyle interventions, statins are routinely used to decrease risk along with aspirin and interventions to control hypertension and diabetes. More than other risk factors, the approach to the identification and treatment of dyslipidemia has been heterogeneous and widely debated. The recent release of the 2013 American College of Cardiology/American Heart Association dyslipidemia guidelines has reignited the controversy over the best approach for risk stratification and treatment. In this article we review the importance of statin therapy for global cardiovascular risk reduction, compare the Canadian Cardiovascular Society dyslipidemia guidelines with other standards, and discuss the points of debate. Despite the seeming variety of recommendations, their common link is a systematic approach to risk stratification and treatment, which will continue to benefit our patients at risk. Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Combined hormonal contraceptive use among women with known dyslipidemias: a systematic review of critical safety outcomes.

PubMed

Dragoman, Monica; Curtis, Kathryn M; Gaffield, Mary E

2016-09-01

Dyslipidemias represent a spectrum of lipid disorders that are important risk factors for cardiovascular disease. In addition, elevated triglycerides are known to be associated with pancreatitis. Though less clear, it is possible that dyslipidemias may also contribute to risk for venous thromboembolism (VTE). Ethinyl estradiol and progestogen, contained within combined hormonal contraception, are known to impact lipid metabolism. To evaluate from the literature whether use of combined hormonal contraception (CHC), including combined oral contraception (COC) pills, transdermal patch, vaginal ring or injectables, modifies the relative risk of acute myocardial infarction (MI), stroke, VTE or pancreatitis among women with known dyslipidemias and to determine if existing lipid abnormalities worsen with CHC use. PubMed and the Cochrane Library databases were searched for all articles in all languages published between inception and September 2014 relevant to dyslipidemia, CHC use and serious adverse events (MI, stroke, VTE or pancreatitis). The quality of each individual study was assessed using the system for grading evidence developed by the United States Preventive Services Task Force. From 306 articles identified by our search strategy, 3 articles met inclusion criteria. In a poor-quality case-control study, women with hypercholesterolemia but no COC use had an increased risk of MI (adjusted odds ratio [adj OR] 3.3, 95% confidence interval [CI] 1.6-6.8), as did women who used COCs but did not have hypercholesterolemia (adj OR 2.0, 95% CI 1.4-2.8), compared with non-COC users without hypercholesterolemia; women with both COC use and hypercholesterolemia had an adjusted OR of 24.7 (95% CI 5.6-108.5) compared with women with neither risk factor. A poor-quality cohort study examined COC users and reported that women with dyslipidemia had increased risk for VTE [crude risk ratio (RR) 1.39, 95% CI 1.04-1.85] and transient ischemic attacks or cerebrovascular accidents (CVAs

Association between Eight Functional Polymorphisms and Haplotypes in the Cholesterol Ester Transfer Protein (CETP) Gene and Dyslipidemia in National Minority Adults in the Far West Region of China.

PubMed

Guo, Shuxia; Hu, Yunhua; Ding, Yusong; Liu, Jiaming; Zhang, Mei; Ma, Rulin; Guo, Heng; Wang, Kui; He, Jia; Yan, Yizhong; Rui, Dongsheng; Sun, Feng; Mu, Lati; Niu, Qiang; Zhang, Jingyu; Li, Shugang

2015-12-16

We have investigated the relationship between the polymorphisms and haplotypes in the CETP gene, and dyslipidemia among the Xinjiang Kazak and Uyghur populations in China. A total of 712 patients with dyslipidemia and 764 control subjects of CETP gene polymorphism at rs12149545, rs3764261, rs1800775, rs711752, rs708272, rs289714, rs5882, and rs1801706 loci were studied by the Snapshot method, linkage disequilibrium analysis and haplotype construction. The results are as follows: (1) the minor allele of eight loci of frequencies in the two groups were different from other results of similar studies in other countries; (2) In the linear regression analysis, the HDL-C levels of rs708272 TT, rs1800775 AA, rs289714 CC and rs711752 AA genotypes were significantly higher than those of other genotypes, however, the rs3764261 GG and rs12149545 GG genotypes were significantly lower than those of other genotypes in the two ethnic groups. The HDL-C levels of the rs12149545 GG genotype were lower than those of other genotypes; (3) in the control group, the rs708272 CT genotype of TG levels were lower than in the CC genotype, the T genotype of LDL-C levels were lower than in the CC genotype, and the HDL-C levels were higher than in the CT genotype; the rs1800775 AC genotype of TG levels were higher than in the AA genotype, the rs711752 AG genotype of TG levels were lower than in the GG genotype, the AA genotype LDL-C levels were lower than in the GG genotype, and the HDL-C levels were higher than in the AG genotype; the rs1800775 AC genotype of TG levels were higher than in the AA genotype. In the dyslipidemia group, the rs708272 TT genotype of TC and LDL-C levels were higher than in the CT genotype and the rs3764261 TT genotype of TC levels were higher than in the GG genotype. The rs711752 AA genotype of TC and LDL-C levels were higher than in the AG genotype, and the rs12149545 AA genotype of TC and LDL-C levels were higher than in the GG genotype; (4) perfect Linkage

Association between Eight Functional Polymorphisms and Haplotypes in the Cholesterol Ester Transfer Protein (CETP) Gene and Dyslipidemia in National Minority Adults in the Far West Region of China

PubMed Central

Guo, Shuxia; Hu, Yunhua; Ding, Yusong; Liu, Jiaming; Zhang, Mei; Ma, Rulin; Guo, Heng; Wang, Kui; He, Jia; Yan, Yizhong; Rui, Dongsheng; Sun, Feng; Mu, Lati; Niu, Qiang; Zhang, Jingyu; Li, Shugang

2015-01-01

We have investigated the relationship between the polymorphisms and haplotypes in the CETP gene, and dyslipidemia among the Xinjiang Kazak and Uyghur populations in China. A total of 712 patients with dyslipidemia and 764 control subjects of CETP gene polymorphism at rs12149545, rs3764261, rs1800775, rs711752, rs708272, rs289714, rs5882, and rs1801706 loci were studied by the Snapshot method, linkage disequilibrium analysis and haplotype construction. The results are as follows: (1) the minor allele of eight loci of frequencies in the two groups were different from other results of similar studies in other countries; (2) In the linear regression analysis, the HDL-C levels of rs708272 TT, rs1800775 AA, rs289714 CC and rs711752 AA genotypes were significantly higher than those of other genotypes, however, the rs3764261 GG and rs12149545 GG genotypes were significantly lower than those of other genotypes in the two ethnic groups. The HDL-C levels of the rs12149545 GG genotype were lower than those of other genotypes; (3) in the control group, the rs708272 CT genotype of TG levels were lower than in the CC genotype, the T genotype of LDL-C levels were lower than in the CC genotype, and the HDL-C levels were higher than in the CT genotype; the rs1800775 AC genotype of TG levels were higher than in the AA genotype, the rs711752 AG genotype of TG levels were lower than in the GG genotype, the AA genotype LDL-C levels were lower than in the GG genotype, and the HDL-C levels were higher than in the AG genotype; the rs1800775 AC genotype of TG levels were higher than in the AA genotype. In the dyslipidemia group, the rs708272 TT genotype of TC and LDL-C levels were higher than in the CT genotype and the rs3764261 TT genotype of TC levels were higher than in the GG genotype. The rs711752 AA genotype of TC and LDL-C levels were higher than in the AG genotype, and the rs12149545 AA genotype of TC and LDL-C levels were higher than in the GG genotype; (4) perfect Linkage

Obesity and Dyslipidemia in South Asians

PubMed Central

Misra, Anoop; Shrivastava, Usha

2013-01-01

Obesity and dyslipidemia are emerging as major public health challenges in South Asian countries. The prevalence of obesity is more in urban areas than rural, and women are more affected than men. Further, obesity in childhood and adolescents is rising rapidly. Obesity in South Asians has characteristic features: high prevalence of abdominal obesity, with more intra-abdominal and truncal subcutaneous adiposity than white Caucasians. In addition, there is greater accumulation of fat at “ectopic” sites, namely the liver and skeletal muscles. All these features lead to higher magnitude of insulin resistance, and its concomitant metabolic disorders (the metabolic syndrome) including atherogenic dyslipidemia. Because of the occurrence of type 2 diabetes, dyslipidemia and other cardiovascular morbidities at a lower range of body mass index (BMI) and waist circumference (WC), it is proposed that cut-offs for both measures of obesity should be lower (BMI 23–24.9 kg/m2 for overweight and ≥25 kg/m2 for obesity, WC ≥80 cm for women and ≥90 cm for men for abdominal obesity) for South Asians, and a consensus guideline for these revised measures has been developed for Asian Indians. Increasing obesity and dyslipidemia in South Asians is primarily driven by nutrition, lifestyle and demographic transitions, increasingly faulty diets and physical inactivity, in the background of genetic predisposition. Dietary guidelines for prevention of obesity and diabetes, and physical activity guidelines for Asian Indians are now available. Intervention programs with emphasis on improving knowledge, attitude and practices regarding healthy nutrition, physical activity and stress management need to be implemented. Evidence for successful intervention program for prevention of childhood obesity and for prevention of diabetes is available for Asian Indians, and could be applied to all South Asian countries with similar cultural and lifestyle profiles. Finally, more research on

Genetic Predisposition to Dyslipidemia and Risk of Preeclampsia.

PubMed

Spracklen, Cassandra N; Saftlas, Audrey F; Triche, Elizabeth W; Bjonnes, Andrew; Keating, Brendan; Saxena, Richa; Breheny, Patrick J; Dewan, Andrew T; Robinson, Jennifer G; Hoh, Josephine; Ryckman, Kelli K

2015-07-01

Large epidemiologic studies support the role of dyslipidemia in preeclampsia; however, the etiology of preeclampsia or whether dyslipidemia plays a causal role remains unclear. We examined the association between the genetic predisposition to dyslipidemia and risk of preeclampsia using validated genetic markers of dyslipidemia. Preeclampsia cases (n = 164) and normotensive controls (n = 110) were selected from live birth certificates to nulliparous Iowa women during the period August 2002 to May 2005. Disease status was verified by medical chart review. Genetic predisposition to dyslipidemia was estimated by 4 genetic risk scores (GRS) (total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglycerides) on the basis of established loci for blood lipids. Logistic regression analyses were used to evaluate the relationships between each of the 4 genotype scores and preeclampsia. Replication analyses were performed in an independent, US population of preeclampsia cases (n = 516) and controls (n = 1,097) of European ancestry. The GRS related to higher levels of TC, LDL-C, and triglycerides demonstrated no association with the risk of preeclampsia in either the Iowa or replication population. The GRS related to lower HDL-C was marginally associated with an increased risk for preeclampsia (odds ratio (OR) = 1.03, 95% confidence interval (CI) = 0.99-1.07; P = 0.10). In the independent replication population, the association with the HDL-C GRS was also marginally significant (OR = 1.03, 95% CI: 1.00-1.06; P = 0.04). Our data suggest a potential effect between the genetic predisposition to dyslipidemic levels of HDL-C and an increased risk of preeclampsia, and, as such, suggest that dyslipidemia may be a component along the causal pathway to preeclampsia. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dyslipidemia in women with polycystic ovary syndrome.

PubMed

Kim, Jin Ju; Choi, Young Min

2013-05-01

Dyslipidemia is a very common metabolic abnormality in women with polycystic ovary syndrome (PCOS). Insulin resistance is a key pathophysiology of PCOS, thus dyslipidemia in women with PCOS may be consistent with those found in an insulin resistant state. In recent meta-analysis, triglycerides and low-density lipoprotein (LDL) cholesterol levels were 26 mg/dL and 12 mg/dL higher, and high-density lipoprotein cholesterol concentration was 6 mg/dL lower in women with PCOS than those of controls. Alterations in LDL quality also have been reported in women with PCOS: women with PCOS have an increased proportion of atherogenic small dense LDL or decreased mean LDL particle size. However, in a recent Korean study, non-obese Korean women with PCOS had no significant quantitative or qualitative changes in LDL cholesterol profile. Lipoprotein (a) has been identified as an independent risk factor for coronary heart disease, and its elevation in PCOS patients has been consistently reported in diverse studies including non-obese Korean population. Some studies have investigated apolipoprotein (Apo) A-I and ApoC-I levels in women with PCOS and levels of ApoA-I, which has cardio-protective effects, were significantly lower in women with PCOS than those of controls. ApoC-I is known to increase the postprandial serum lipid level that is common in coronary artery disease patients, and one study reported that such an elevation may be the earliest variation of lipid abnormality in women with PCOS. In conclusion, women with PCOS should receive a complete lipid test, and lifestyle modification, including diet and exercise, is the first line therapy for all women with PCOS and is particularly important for those with dyslipidemia.

Selenium Level and Dyslipidemia in Rural Elderly Chinese

PubMed Central

Su, Liqin; Gao, Sujuan; Unverzagt, Frederick W.; Cheng, Yibin; Hake, Ann M.; Xin, Pengju; Chen, Chen; Liu, Jingyi; Ma, Feng; Bian, Jianchao; Li, Ping; Jin, Yinlong

2015-01-01

Objective Higher selenium level has been hypothesized to have the potential to reduce the risk of cardiovascular diseases including dyslipidemia. However, results from previous studies are inconsistent. This study aims to determine the association between selenium level and dyslipidemia in elderly Chinese with relatively low selenium status. Methods A cross-sectional study of 1859 participants aged 65 or older from four rural counties in China was conducted. Serum total cholesterol (TC), triglycerides (TG), high density lipoprotein-cholesterol (HDLC) and low-density lipoprotein-cholesterol (LDLC), nail selenium concentration and APOE genotype were measured in all subjects. The four types of dyslipidemia were defined as >5.17mmol/L for High-TC, >1.69 mmol/L for High-TG, >3.36 mmol/L for High-LDLC, and <1.04 mmol/L for Low-HDLC according to Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults. Logistic models adjusting for age, gender, APOE genotype, body mass index, alcohol consumption, smoking, physical activity, medication use for cardiovascular diseases were used to examine the relationship between selenium levels and the risk of dyslipidemia. Results Mean nail selenium concentration was 0.465μg/gin this sample. Rates for High-TC, High-LDLC, High-TG, Low-HDLC were 18.13%, 13.23%, 12.21% and 32.76% respectively. Results from logistic models indicated that higher selenium levels were significantly associated with higher risk of High-TC, High-LDLC and lower risk of Low-HDLC adjusting for covariates (p < 0.0001). Compared with the lowest selenium quartile group, participants in selenium quartile groups 2, 3 and 4 had significantly higher rates of High-TC, High-LDLC, High-TG, and lower rate of Low-HDLC adjusting for covariates. No significant association was observed between selenium level and the risk of High-TG. APOEε4 carriers had higher rates of High-TC and High-LDLC. There was no interaction between selenium level and APOE with the rates of

[Dyslipidemias in school-age chilean children: prevalence and associated factors].

PubMed

Barja Yáñez, Salesa; Arnaiz Gómez, Pilar; Villarroel Del Pino, Luis; Domínguez de Landa, Angélica; Castillo Valenzuela, Oscar; Farías Jofré, Marcelo; Mardones Santander, Francisco

2015-05-01

Dyslipidemias are a key cardiovascular risk factor, and are increased since early childhood. The objective of this study was to describe the prevalence, characteristics of dyslipidemias and associated factors in a population of Chilean children. Cross-sectional study done in school-age children from Santiago, Chile (2009-2011). Parents answered questions about family medical history and children answered questions about physical activity. Anthropometry was performed and in a blood sample (12 hours fast) lipid profile, glycemia and insulinemia were measured. We recruited 2900 euglycemic children, 11.4 ± 0.97 years old, 52% girls. According to BMI, 22.5% were overweight and 15,3% had obesity. Considering recommended cut-off points for lipids, 69.3% were in acceptable range, 19.2% at risk and 11.5% at high cardiovascular risk. In total, 32% of the population had any clinical form of dyslipidemia: Isolated hypertriglyceridemia (9.4%), low HDL-C (7.6%), isolated hypercholesterolemia (4.9%), atherogenic dyslipidemia (6.24%) and mixed dyslipidemia (3.9%). Except for isolated hypercholesterolemia, dyslipidemias were more frequent in girls (globally 36.2% vs. 27.4%, p<0.0001). Low HDL-C was associated with sedentary lifestyle. In multiple logistic regression analysis, nutritional status was the most important associated factor, with less influence of age, sex, central obesity, insulin resistance and history of parental cardiovascular risk factors. In this population of Chilean school-age children, we found a high prevalence of dyslipidemia, and the principal determinant was weight excess. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Prevalence of Dyslipidemia and Associated Factors in Obese Children and Adolescents.

PubMed

Elmaoğulları, Selin; Tepe, Derya; Uçaktürk, Seyit Ahmet; Karaca Kara, Fatma; Demirel, Fatma

2015-09-01

Childhood-onset obesity is associated with increased mortality and morbidity related to cardiovascular diseases (CVD) during adulthood. Dyslipidemia has a fundamental role in the pathogenesis of CVD. This study aimed to evaluate the prevalence of dyslipidemia and related factors among obese children and adolescents. Obese patients aged between 2 and 18 years were included in the study. Serum concentrations of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), fasting glucose levels, insulin, thyroid-stimulating hormone (TSH), free thyroxine (fT4), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and liver ultrasound findings were evaluated retrospectively. Among 823 obese patients, 353 (42.9%) met the dyslipidemia criteria: 21.7% had hypertriglyceridemia, 19.7% had low levels of HDL-C, 18.6% had hypercholesterolemia, and 13.7% had high levels of LDL-C. Older age and/or high body mass index (BMI) were related to increased prevalence of dyslipidemia. Hepatosteatosis was more common among dyslipidemic patients. The frequency of insulin resistance (IR) and of higher levels of ALT and TSH were also detected in dyslipidemic patients. Patients with both dyslipidemia and grade 2-3 hepatosteatosis had higher levels of ALT, AST and TSH and lower levels of fT4. Prevalence of dyslipidemia is high in obese children, and hypertriglyceridemia is in the foreground. Higher levels of IR and more apparent abnormal liver function test results are observed in the context of dyslipidemia and hepatosteatosis coexistence. Metabolic and hormonal alterations related with thyroid functions may also be associated with dyslipidemia and hepatosteatosis in obese patients.

Prevalence of dyslipidemia and metabolic syndrome risk factor in overweight and obese children.

PubMed

Casavalle, Patricia L; Lifshitz, Fima; Romano, Laura S; Pandolfo, Marcela; Caamaño, Anabella; Boyer, Patricia M; Rodríguez, Patricia N; Friedman, Silvia M

2014-12-01

To study the prevalence of dyslipidemia and metabolic syndrome risk factors in overweight/ obese children and adolescents. The study included 139 healthy white Argentinean children/adolescents (aged 8-14 years) who were overweight (n = 30) or obese (n = 109), based on BMI z score according to WHO, 2007. Children were referred to the Nutrition Clinic, San Martin University Hospital, Buenos Aires, Argentina for evaluation and treatment. Dyslipidemia was considered when one or more serum lipids (mg/dL) were out of range: total cholesterol ≥ 200, high-density lipoprotein (HDL-C) ≤ 40, triglycerides (TG) > 110, low-density lipoprotein (LDL-C) > 130 or non-HDL-C > 145 and fasting blood glucose (FBG) > 110. Additional metabolic syndrome risk factors included: increased waist circumference (WC, ≥ 90th percentile) and high blood pressure (> 90th percentile). A history of low birth weight (< 2.5 kg) and a family history of: dyslipidemia (FHDL), premature acute myocardial infarction (FHPAMI) and/or type 2 diabetes mellitus (FHT2DM) were also assessed. The prevalence of dyslipidemia among overweight and obese children was 50.4% and its pattern was: hypertriglyceridemia 31.9%, low HDL-C 29.7%, high non-HDL-C 15.8%, hypercholesterolemia 11.9%, and elevated LDL-C 10.7%. The dyslipidemia was more often detected among those with increased WC (55.4%), FHDL (51.1%), and FHT2DM (48%); prevalence was lower in those with FHPAMI (18.7%) and low birth weight (4.3%). Most children presented a variety of metabolic syndrome risk factors; only 25.8% did not have any such alterations identified. BMI z score showed a positive association with TG and negative with HDL-C. Overweight and obesity increased the odds ratios of metabolic syndrome risk factors, hypertriglyceridemia and low HDL-C. Overweight/obese children were prone to have dyslipidemia and metabolic syndrome. Excess body weight is an important harbinger of health that requires the assessment of multiple parameters to discern

Screening for Dyslipidemia in Younger Adults: A Systematic Review for the U.S. Preventive Services Task Force.

PubMed

Chou, Roger; Dana, Tracy; Blazina, Ian; Daeges, Monica; Bougatsos, Christina; Jeanne, Thomas L

2016-10-18

Dyslipidemia may occur in younger adults (defined as persons aged 21 to 39 years) and is an important risk factor for cardiovascular disease. Screening might identify younger adults with asymptomatic dyslipidemia who may benefit from lipid-lowering therapies. To update the 2008 U.S. Preventive Services Task Force review on dyslipidemia screening in younger adults. The Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and MEDLINE through May 2016, and reference lists. Randomized, controlled trials; cohort studies; and case-control studies on screening for or treatment of asymptomatic dyslipidemia in adults aged 21 to 39 years. The plan was for 1 investigator to abstract data and a second to check their accuracy, and for 2 investigators to independently assess study quality; however, no studies met the inclusion criteria. No study evaluated the effects of lipid screening versus no screening, treatment versus no treatment, or delayed versus earlier treatment on clinical outcomes in younger adults. In addition, no study evaluated the diagnostic yield of alternative screening strategies (such as targeted screening of persons with a family history of hyperlipidemia vs. general screening) in younger adults. No direct relevant evidence. Direct evidence on the benefits and harms of screening for or treatment of dyslipidemia in younger adults remains unavailable. Estimating the potential effects of screening for dyslipidemia in this population requires extrapolation from studies performed in older adults. Agency for Healthcare Research and Quality.

Dyslipidemia and its therapeutic challenges in renal transplantation.

PubMed

Riella, L V; Gabardi, S; Chandraker, A

2012-08-01

Cardiovascular disease is the leading cause of mortality in kidney transplant recipients. Dyslipidemia is a common finding after renal transplantation and a significant risk factor in the development of coronary heart disease. Although a causal relationship with cardiovascular mortality has not been proven in the transplant population, it is reasonable to extrapolate data from the general population and aggressively treat posttransplant dyslipidemia. Statins are considered the agents of choice, though their use may be complicated by drug misadventures. Pravastatin, fluvastatin and pitavastatin are considered to be the safest statins to use in this population; however, given their low-potency, a high-potency statin, such as atorvastatin, may be necessary in patients with significant dyslipidemia. In this article, we discuss the etiology of and treatment strategies for dyslipidemia in renal transplant recipients based on a literature review of potential therapeutic adverse effects and benefits in this population. We will also evaluate the reasons for and consequences of the latest Food and Drug Administration (FDA) warnings regarding the use of simvastatin. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

Prevalence of dyslipidemia in Iranian children and adolescents: A systematic review.

PubMed

Hovsepian, Silva; Kelishadi, Roya; Djalalinia, Shirin; Farzadfar, Farshad; Naderimagham, Shohreh; Qorbani, Mostafa

2015-05-01

Dyslipidemia is considered as an important modifiable risk factor for cardiovascular disease (CVD). The link between childhood dyslipidemia and occurrence of atherosclerosis and its sequels in adulthood are well-documented. This study aimed to systematically review the prevalence of dyslipidemia among Iranian children and adolescents. An electronic search was conducted on studies published from January 1990 to January 2014. The main international electronic data sources were PubMed and the NLM Gateway (for MEDLINE), Institute of Scientific Information (ISI), and SCOPUS. For Persian databases, we used domestic databases with systematic search capability including IranMedex, Irandoc, and Scientific Information Database (SID). We included all available population-based studies and national surveys conducted in the pediatric age group (aged <21 years). In this review, 1772 articles were identified (PubMed: 1464; Scopus: 11; ISI: 58; SID: 90; IranMedex: 149; Irandoc: 57). During three refine steps and after removing of duplicates, 182 articles related to the study domain were selected. After quality assessment, 46 studies were selected for text appraisal, of which 26 qualified articles were evaluated at the final step. The prevalence range of hypercholesterolemia, hypertriglyceridemia, elevated low-density lipoprotein cholesterol, and low high-density lipoprotein cholesterol (HDL-C) were 3-48%, 3-50%, 5-20% and 5-88%, respectively. Low HDL-C and hypertriglyceridemia were the most prevalent lipid disorders in this group of population. Dyslipidemia is a common health problem among Iranian children and adolescents. Few data were available in preschool children. This finding provides useful information for health policy makers to implement action-oriented interventions for prevention and early control of this important CVD risk factor.

Use of expert consensus to improve atherogenic dyslipidemia management.

PubMed

Millán Núñez-Cortés, Jesús; Pedro-Botet, Juan; Brea-Hernando, Ángel; Díaz-Rodríguez, Ángel; González-Santos, Pedro; Hernández-Mijares, Antonio; Mantilla-Morató, Teresa; Pintó-Sala, Xavier; Simó, Rafael

2014-01-01

Although atherogenic dyslipidemia is a recognized cardiovascular risk factor, it is often underassessed and thus undertreated and poorly controlled in clinical practice. The objective of this study was to reach a multidisciplinary consensus for the establishment of a set of clinical recommendations on atherogenic dyslipidemia to optimize its prevention, early detection, diagnostic evaluation, therapeutic approach, and follow-up. After a review of the scientific evidence, a scientific committee formulated 87 recommendations related to atherogenic dyslipidemia, which were grouped into 5 subject areas: general concepts (10 items), impact and epidemiology (4 items), cardiovascular risk (32 items), detection and diagnosis (19 items), and treatment (22 items). A 2-round modified Delphi method was conducted to compare the opinions of a panel of 65 specialists in cardiology (23%), endocrinology (24.6%), family medicine (27.7%), and internal medicine (24.6%) on these issues. After the first round, the panel reached consensus on 65 of the 87 items discussed, and agreed on 76 items by the end of the second round. Insufficient consensus was reached on 3 items related to the detection and diagnosis of atherogenic dyslipidemia and 3 items related to the therapeutic goals to be achieved in these patients. The external assessment conducted by experts on atherogenic dyslipidemia showed a high level of professional agreement with the proposed clinical recommendations. These recommendations represent a useful tool for improving the clinical management of patients with atherogenic dyslipidemia. A detailed analysis of the current scientific evidence is required for those statements that eluded consensus. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

The correlation between serum free thyroxine and regression of dyslipidemia in adult males: A 4.5-year prospective study.

PubMed

Wang, Haoyu; Liu, Aihua; Zhou, Yingying; Xiao, Yue; Yan, Yumeng; Zhao, Tong; Gong, Xun; Pang, Tianxiao; Fan, Chenling; Zhao, Jiajun; Teng, Weiping; Shan, Zhongyan; Lai, Yaxin

2017-09-01

Elevated free thyroxine (FT4) levels may play a protective role in development of dyslipidemia. However, few prospective studies have been performed to definite the effects of thyroid hormones on the improvement of dyslipidemia and its components. Thus, this study aims to clarify the association between thyroid hormones within normal range and reversal of dyslipidemia in the absence of intervention.A prospective analysis including 134 adult males was performed between 2010 and 2014. Anthropometric parameters, thyroid function, and lipid profile were measured at baseline and during follow-up. Logistic regression and receiver operating characteristic (ROC) analysis were conducted to identify the variables in forecasting the reversal of dyslipidemia and its components.During 4.5-year follow-up, 36.6% (49/134) patients resolved their dyslipidemia status without drug intervention. Compared with the continuous dyslipidemia group, subjects in reversal group had elevated FT4 and high-density lipoprotein cholesterol (HDL-C) levels, as well as decreased total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels at baseline. Furthermore, baseline FT4 is negatively associated with the change percentages of TG (r = -0.286, P = .001), while positively associated with HDL-C (r = 0.227, P = .008). However, no correlation of lipid profile change percentages with FT3 and TSH were observed. Furthermore, the improving effects of baseline FT4 on dyslipidemia, high TG, and low HDL-C status were still observed after multivariable adjustment. In ROC analysis, areas under curve (AUCs) for FT4 in predicting the reversal of dyslipidemia, high TG, and low HDL-C were 0.666, 0.643, and 0.702, respectively (P = .001 for dyslipidemia, .018 for high TG, and .001 for low HDL-C).Higher FT4 value within normal range may ameliorate the dyslipidemia, especially high TG and low HDL-C status, in males without drug intervention. This suggests

Dyslipidemia prevalence, treatment, control, and awareness in the Canadian Health Measures Survey.

PubMed

Joffres, Michel; Shields, Margot; Tremblay, Mark S; Connor Gorber, Sarah

2013-04-24

The most recent Canadian population-level data on lipid levels are from 1992. This study presents current estimates of Canadians with dyslipidemia, the proportion aware of their condition, and the proportion being treated and below target values. The Canadian Health Measures Survey (2007-2009) assessed the prevalence, awareness and treatment of dyslipidemia. Dyslipidemia was defined as TC/HDL-C ratio ≥5; measured LDL-C ≥3.5 mmol/L; or taking lipid-modifying medications. The 2009 guidelines for the diagnosis and treatment of dyslipidemia were used to define low, moderate or high cardiovascular disease (CVD) risk and treatment initiation and targets. Forty-five percent of Canadians aged 18-79 years have dyslipidemia. Fifty-seven percent of respondents were not aware of their condition. Lipid-modifying therapy was initiated in individuals where treatment would be recommended in 49%, 20% and 54% of those at high, moderate, and low risk levels, respectively. The majority (81%) of those taking medication had their lipid levels under desirable levels, however, only 24% of those with dyslipidemia reported medication use. Overall, only 19% of those with dyslipidemia had their lipids under recommended levels. Only 41% of those taking lipid-modifying medication reached a recommended target of LDL-C <2 mmol/L or ApoB <0.8 g/L. There is still a high proportion of Canadians at high risk of CVD, with dyslipidemia, who are not being treated to recommended levels. These data need to be integrated into CVD reduction recommendations and represent an important baseline for assessing progress.

Genome-wide association study in discordant sibships identifies multiple inherited susceptibility alleles linked to lung cancer.

PubMed

Galvan, Antonella; Falvella, Felicia S; Frullanti, Elisa; Spinola, Monica; Incarbone, Matteo; Nosotti, Mario; Santambrogio, Luigi; Conti, Barbara; Pastorino, Ugo; Gonzalez-Neira, Anna; Dragani, Tommaso A

2010-03-01

We analyzed a series of young (median age = 52 years) non-smoker lung cancer patients and their unaffected siblings as controls, using a genome-wide 620 901 single-nucleotide polymorphism (SNP) array analysis and a case-control DNA pooling approach. We identified 82 putatively associated SNPs that were retested by individual genotyping followed by use of the sib transmission disequilibrium test, pointing to 36 SNPs associated with lung cancer risk in the discordant sibs series. Analysis of these 36 SNPs in a polygenic model characterized by additive and interchangeable effects of rare alleles revealed a highly statistically significant dosage-dependent association between risk allele carrier status and proportion of cancer cases. Replication of the same 36 SNPs in a population-based series confirmed the association with lung cancer for three SNPs, suggesting that phenocopies and genetic heterogeneity can play a major role in the complex genetics of lung cancer risk in the general population.

[Prevalence of dyslipidemia in the rural population of Gueoul (Senegal)].

PubMed

Thiombiano, L P; Mbaye, A; Sarr, S A; Ngaide, A A; Kane, Ab; Diao, M; Kane, Ad; Ba, S A

2016-04-01

The cardiovascular risk factors are clearly increasing in developing countries. Among these factors, dyslipidemia is often found, this due to the change in behavioral and dietary habits (OMS, 2006). Dyslipidemia is a "primary or secondary pathological changes in serum lipids". It is a chronic and metabolic abnormality, characterized by persistently elevated TG, LDL-c, and a decrease in HDL (Attias et al., 2013-2014). The objective of this study is to determine the prevalence of dyslipidemia, and give the lipid profile of the population in Gueoul. We performed a comprehensive observational study, cross-sectional descriptive on Senegalese aged 35 or over, living in Gueoul for at least 6 months. Lipid profile (total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol) was systematically after 12hours of fasting. Dyslipidemia was found in 61.3 % of cases with 50 % pure hypercholesterolemia (n=705). Only 20 subjects (2.3 %) knew they had dyslipidemia. The detection rate was 59.8 % (n=844). The type most represented was hypoHDLemia (45.6 %) followed by hyperLDLemia (28.8 %). Triglycerides were increased in only 2.8 % of cases. The prevalence of dyslipidemia is very high in our regions. It is often associated with female gender, hypertension, diabetes, and obesity. Its main causes are physical inactivity, change in lifestyle and eating habits. It is often misunderstood and its management is limited in most cases to low-calorie diet. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Relationship between Serum Ferritin Levels and Dyslipidemia in Korean Adolescents

PubMed Central

Kim, Young-Eun; Roh, Yong-Kyun; Ju, Sang-Yhun; Yoon, Yeo-Joon; Nam, Ga-Eun; Nam, Hyo-Yun; Choi, Jun-Seok; Lee, Jong-Eun; Sang, Jung-Eun; Han, Kyungdo

2016-01-01

Background Ferritin is associated with various cardiometabolic risk factors such as dyslipidemia, hypertension, obesity, and insulin resistance in adults. We aimed to study the association between serum ferritin levels and dyslipidemia in adolescents, because dyslipidemia is considered an important modifiable cardiovascular risk factor in the young. Methods We analyzed 1,879 subjects (1,026 boys and 853 girls) from the 2009–2010 Korean National Health and Nutrition Examination Survey IV. Subjects were categorized into quartiles according to their lipid parameters, which were classified according to age and gender. Those in the highest quartile groups for total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride concentrations were diagnosed as having dyslipidemia. Those in the lowest quartile for high-density lipoprotein cholesterol (HDL-C) values were diagnosed with abnormal levels. Results In boys, total cholesterol, LDL-C, and triglyceride concentrations were significantly correlated with serum ferritin levels. In both boys and girls, serum ferritin levels were negatively associated with HDL-C values, even after adjusting for all covariates. Furthermore, there was no significant correlation between serum ferritin levels and total cholesterol, LDL, and triglyceride concentrations in girls. Conclusion Serum ferritin levels were significantly associated with major dyslipidemia parameters, more prominently in boys than in girls, and this association represents a cardiometabolic risk factor. PMID:27070153

Antiretroviral treatment-induced dyslipidemia in HIV-infected patients is influenced by the APOC3-related rs10892151 polymorphism.

PubMed

Aragonès, Gerard; Alonso-Villaverde, Carlos; Pardo-Reche, Pedro; Rull, Anna; Beltrán-Debón, Raúl; Rodríguez-Gallego, Esther; Fernández-Sender, Laura; Camps, Jordi; Joven, Jorge

2011-09-22

The recently observed association between the APOC3-related rs10892151 polymorphism and serum triglyceride levels has prompted us the possibility to explore whether this genetic variant may play a major role in human immunodeficiency virus (HIV)/antiretroviral therapy-induced dyslipidemia. We determined the rs10892151 genotype distribution and serum apolipoprotein (apo) C-III concentration in a group of HIV-infected patients (n = 208) and in a group of age and sex-matched healthy volunteers (n = 200). Circulating lipid and lipoprotein levels were followed for 12 months after antiretroviral treatment initiation in the HIV-infected group. There were no significant variations in the frequency of the A allele between the healthy and HIV-infected groups (7.5 vs. 8.6%, respectively; p = 0.7); additionally, the A allele was not related to serum apo C-III concentration. However, among patients receiving protease inhibitor (PI) treatment, carriers of the A allele had significantly increased serum triglyceride (5.76 ± 2.54 mmol/L) and total cholesterol (6.63 ± 2.85 mmol/L) concentrations together with depressed levels of HDL-cholesterol (0.75 ± 0.3 mmol/L) when compared with patients not carrying the allele (2.43 ± 1.32, 5.2 ± 2.17 and 1.24 ± 0.4 mmol/L, respectively) at the end of the study. This effect was only evident for HDL-cholesterol concentration when patients were treated with non-nucleoside reverse transcriptase inhibitors (1.05 ± 0.4 vs. 1.28 ± 0.4 mmol/L). The A allelic variant of the rs10892151 polymorphism is not associated with serum apo C-III concentration, but predisposes HIV-infected patients to less favorable lipid profile, particularly in those patients treated with PIs.

The prevalence, awareness, treatment and control of dyslipidemia among adults in China.

PubMed

Pan, Ling; Yang, Zhenhua; Wu, Yue; Yin, Rui-Xing; Liao, Yunhua; Wang, Jinwei; Gao, Bixia; Zhang, Luxia

2016-05-01

To analyze the prevalence, awareness, treatment, control and epidemiological characteristics of dyslipidemia in Chinese adults. In this cross-sectional study, we adopted a multi-stage, stratified sampling method to obtain representative samples of the general population aged >18 years from different urban and rural regions in China. All subjects completed a lifestyle and medical history questionnaire and were examined for risk factors. Dyslipidemia was defined according to criteria of the 2007 Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults. Continuous variables were compared using variance analysis. Multivariate logistic regression analysis was performed to explore the risk factors of dyslipidemia. The prevalence of dyslipidemia was 34.0% overall, and 35.1%, and 26.3% in urban and rural areas, respectively. The prevalence of dyslipidemia was significantly higher in men than women (41.9% vs 32.5%; P < 0.001). Rates of awareness, treatment, and control were 31.0%, 19.5%, and 8.9%, respectively. Increasing age (OR = 1.012; 95% CI:1.010, 1.014), male sex (OR = 1.411; 95% CI:1.318, 1.510), obesity (OR = 1.424; 95% CI:1.345, 1.507), cardiovascular disease (OR = 1.343; 95% CI:1.125, 1.603), diabetes (OR = 1.955; 95% CI:1.751, 2.182), hypertension (OR = 1.481; 95% CI:1.391, 1.577) and hyperuricemia (OR = 2.223; 95% CI:2.060, 2.399) were independent risk factors of dyslipidemia. The prevalence of dyslipidemia among Chinese adults was high but awareness, treatment, and control of dyslipidemia were low. Urban high income earners and rural medium income earners show higher prevalence. Low income earners in urban and rural population have the worst awareness treatment, and control rate. There is an increased need for closely monitoring and controlling high risk factors in the populations including postmenopausal women, unhealthy lifestyle peoples and patients with chronic non-communicable diseases. Copyright © 2016 Elsevier Ireland

Dyslipidemia in rural areas of North China: prevalence, characteristics, and predictive value.

PubMed

Gao, Nannan; Yu, Yong; Zhang, Bingchang; Yuan, Zhongshang; Zhang, Haiqing; Song, Yongfeng; Zhao, Meng; Ji, Jiadong; Liu, Lu; Xu, Chao; Zhao, Jiajun

2016-09-13

The prevalence of cardiovascular disease has been increasing worldwide. As a common pathogenic risk factor, dyslipidemia played a great role in the incidence and progress of these diseases. We investigated to achieve accurate and up-to-date information on the prevalence of dyslipidemia and its associations with other lipid-related diseases in rural North China. Using a complex, multistage, probability sampling design, we conducted a large-scale cross-sectional study of 8528 rural participants aged over 18 years in Shandong Province. Prevalence and characteristics of dyslipidemia were demonstrated. The odds ratios between dyslipidemia types and lipid-related diseases were further analyzed by logistic regression. Among the overall population, 45.8 % suffered from dyslipidemia. The prevalence of lipid abnormality (including high and very high levels) was 18.6, 12.7, 9.8 and 12.7 % for total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol and triglycerides (TG), respectively. Among all participants with dyslipidemia, 23.9 % were aware, only 11.5 % were treated, 10.0 % were controlled. For subjects with dyslipidemia, the risk for non-alcoholic fatty liver disease (NAFLD) was highest with a 3.3-fold over that of non-dyslipidmia (OR = 3.30, P < 0.001); followed by hyperuricemia and diabetes mellitus (DM), while with 2-fold increase (OR = 1.99, P < 0.001; OR = 1.92, P < 0.001); with only 1.5-fold risk for atherosclerosis (AS) (OR = 1.47, P < 0.001). The presence of high cholesterol was mainly associated with AS, while abnormal TG was correlated with NAFLD and DM. Dyslipidemia has become a serious public health issue in rural North China. The rapid increase of high TC and incremental risk of high TG may contribute to the epidemic of AS, NAFLD and DM. It is imperative to develop individualized prevention and treatment guidelines according to dyslipidemia phenotypes.

Prevalence of Dyslipidemias in Three Regions in Venezuela: The VEMSOLS Study Results

PubMed Central

González-Rivas, Juan P.; Nieto-Martínez, Ramfis; Brajkovich, Imperia; Ugel, Eunice; Rísquez, Alejandro

2018-01-01

Background The prevalence of dyslipidemia in multiple regions of Venezuela is unknown. The Venezuelan Metabolic Syndrome, Obesity and Lifestyle Study (VEMSOLS) was undertaken to evaluate cardiometabolic risk factors in Venezuela. Objective To determine the prevalence of dyslipidemia in five populations from three regions of Venezuela. Methods During the years 2006 to 2010, 1320 subjects aged 20 years or older were selected by multistage stratified random sampling from all households in five municipalities from 3 regions of Venezuela: Lara State (Western region), Merida State (Andean region), and Capital District (Capital region). Anthropometric measurements and biochemical analysis were obtained from each participant. Dyslipidemia was defined according to the NCEP/ATPIII definitions. Results Mean age was 44.8 ± 0.39 years and 68.5% were females. The prevalence of lipids abnormalities related to the metabolic syndrome (low HDL-c [58.6%; 95% CI 54.9 - 62.1] and elevated triglycerides [39.7%; 36.1 - 43.2]) were the most prevalent lipid alterations, followed by atherogenic dyslipidemia (25.9%; 22.7 - 29.1), elevated LDL-c (23.3%; 20.2 - 26.4), hypercholesterolemia (22.2%; 19.2 - 25.2), and mix dyslipidemia (8.9%; 6.8 - 11.0). Dyslipidemia was more prevalent with increasing body mass index. Conclusion Dyslipidemias are prevalent cardiometabolic risk factors in Venezuela. Among these, a higher prevalence of low HDL is a condition also consistently reported in Latin America. PMID:29538522

[Consensus document on the treatment of dyslipidemia in diabetes].

PubMed

Hormigo-Pozo, A; Mancera-Romero, J; Perez-Unanua, M P; Alonso-Fernandez, M; Lopez-Simarro, F; Mediavilla-Bravo, J J

2015-03-01

People with type 2 diabetes mellitus have a 2 to 4 times higher risk of developing cardiovascular diseases when compared to general population of similar age and sex. This risk remains after adjustment of other traditional cardiovascular risk factors. The dyslipidemia associated with type 2 diabetes mellitus is present in up to 60% of people with diabetes and contributes greatly to increased cardiovascular, morbidity and mortality risk in these patients. Diabetic dyslipidemia is a disorder of lipid metabolism characterized by an excess of triglycerides, a decrease in HDL-cholesterol and altered lipoprotein composition, consisting mainly in an excess of small, dense LDL particles. Multiple clinical trials have demonstrated the benefits of drug treatment of dyslipidemia (mainly statins) to prevent cardiovascular events and mortality in people with diabetes, both in primary and secondary prevention. This consensus document, developed by general practitioners, members of the Diabetes Group of the Spanish Society of Primary Care Physicians (SEMERGEN), aims to assist in the management of patients with diabetes and dyslipidemia in accordance with the most recent recommendations. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

Dyslipidemia and its risk factors among urban middle-aged Iranians: A population-based study.

PubMed

Ebrahimi, Hossein; Emamian, Mohammad Hassan; Hashemi, Hassan; Fotouhi, Akbar

2016-01-01

Dyslipidemia is a known risk factor for cardiovascular disease and is a leading cause of mortality in developed and developing countries. This study was aimed to determine the prevalence of dyslipidemia and its risk factors in an urban group of Iranian adult population. In this study, based on the criteria set by the National Cholesterol Education Program, the prevalence of dyslipidemia was evaluated in a population of 4737 people aged 45-69 years who participated in the second phase of an ophthalmology cohort study in Shahroud. Dyslipidemia prevalence was determined by age, sex, and risk factors of the disease; the findings were tested by using simple and multiple logistic regression. The prevalence of dyslipidemia was 66.5% (CI 95%: 64.4-68.6) in males, 61.3% (CI 95%: 59.5-63.2) in females, and 63.4% (CI 95%: 62.0-64.9%) in both sexes. The prevalence of hypertriglyceridemia, hypercholesterolemia, low HDL-C, and high LDL-C, respectively, was 28.8%, 13.4%, 42.3%, and 13.4%, respectively. In multivariate logistic regression model, increase of age (for females), abdominal obesity, overweight and obesity, hypertension, and diabetes were associated with an increased odd of dyslipidemia. The prevalence of dyslipidemia in middle-aged urban population in Iran is high, and with increasing age there is an increased risk of dyslipidemia. Hence, considering the growing trend of aging in Iran, there is need for taking special measures to deal with dyslipidemia as a health priority. Furthermore, the need for planning in order to reduce the risk of dyslipidemia and prevent its complications is greater than ever. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Allele specific expression analysis identifies regulatory variation associated with stress-related genes in the Mexican highland maize landrace Palomero Toluqueño

PubMed Central

González-Segovia, Eric; Ross-Ibarra, Jeffrey; Simpson, June K.

2017-01-01

Background Gene regulatory variation has been proposed to play an important role in the adaptation of plants to environmental stress. In the central highlands of Mexico, farmer selection has generated a unique group of maize landraces adapted to the challenges of the highland niche. In this study, gene expression in Mexican highland maize and a reference maize breeding line were compared to identify evidence of regulatory variation in stress-related genes. It was hypothesised that local adaptation in Mexican highland maize would be associated with a transcriptional signature observable even under benign conditions. Methods Allele specific expression analysis was performed using the seedling-leaf transcriptome of an F1 individual generated from the cross between the highland adapted Mexican landrace Palomero Toluqueño and the reference line B73, grown under benign conditions. Results were compared with a published dataset describing the transcriptional response of B73 seedlings to cold, heat, salt and UV treatments. Results A total of 2,386 genes were identified to show allele specific expression. Of these, 277 showed an expression difference between Palomero Toluqueño and B73 alleles under benign conditions that anticipated the response of B73 cold, heat, salt and/or UV treatments, and, as such, were considered to display a prior stress response. Prior stress response candidates included genes associated with plant hormone signaling and a number of transcription factors. Construction of a gene co-expression network revealed further signaling and stress-related genes to be among the potential targets of the transcription factors candidates. Discussion Prior activation of responses may represent the best strategy when stresses are severe but predictable. Expression differences observed here between Palomero Toluqueño and B73 alleles indicate the presence of cis-acting regulatory variation linked to stress-related genes in Palomero Toluqueño. Considered alongside

[High frequency of dyslipidemia in VIH-infected patients in aa peruvian public hospital].

PubMed

Rondan, Paola L; Flores-Flores, Oscar; Doria, Nicole A; Valencia-Mesias, Gustavo; Chávez-Pérez, Víctor; Soria, Jaime

2017-01-01

The objective of the study was to determine the frequency and characteristics of dyslipidemia in patients with HIV in highly active antiretroviral therapy (HAART) in a Peruvian public hospital. A cross-sectional study was carried out in patients with complete lipid profile after receiving at least six months of HAART. Dyslipidemia was defined according to the criteria of the NCEP-ATP III. We reviewed 2 975 clinical histories, and included 538 (18.1%) in the analysis. The frequency of dyslipidemia was 74.7%. HAART regimens which include protease inhibitors (PI) (odds ratio [OR]: 1.22; confidence interval at 95% [CI 95%]: 1.11-1.33) and to be older than 40 years (OR: 1.17; CI 95%: 1.05-1.28) were associated with dyslipidemia, adjusted by viral load, CD4 lymphocyte level and gender. In conclusion, dyslipidemia was very common in our sample and was mainly associated with the use of PI. It is necessary to promote the dyslipidemia control as part of the comprehensive care of the patient with HIV.

New Frontiers in the Treatment of Diabetic Dyslipidemia

PubMed Central

Wang, Shu-Yi; Hsieh, Ming-Chia; Tu, Shih-Te; Chuang, Chieh-Sen

2013-01-01

Dyslipidemia is a major risk factor for cardiovascular complications in people with diabetes. Lowering low-density lipoprotein cholesterol (LDL-C) levels is effective in the primary and secondary prevention of diabetic vascular complications. However, LDL-C levels do not reflect all aspects of diabetic dyslipidemia, which is characterized by hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C). Statins, nicotinic acid, and fibrates play a role in treating diabetic dyslipidemia. Atherosclerosis is a major disorder of the blood vessel wall in patients with diabetes. A number of antihyperlipidemic agents may be beneficial and exhibit effects at the actual site of vascular disease and not only on plasma lipoprotein concentrations. Several novel therapeutic compounds are currently being developed. These include additional therapeutics for LDL-C, triglycerides, HDL-C, and modulators of inflammation that can be used as possible synergic agents for the treatment of atherosclerosis and irregularities in plasma lipoprotein concentrations. PMID:24380093

Alcohol Drinking, Dyslipidemia, and Diabetes: A Population-based Prospective Cohort Study among Inner Mongolians in China.

PubMed

Liang, Zhu; Qiu, Qiao Yan; Wu, Jia Hui; Zhou, Jing Wen; Xu, Tian; Zhang, Ming Zhi; Zhang, Yong Hong; Zhang, Shao Yan

2016-08-01

No previous studies have evaluated the association between dyslipidemia, alcohol drinking, and diabetes in an Inner Mongolian population. We aimed to evaluate the co-effects of drinking and dyslipidemia on diabetes incidence in this population. The present study was based on 1880 participants from a population-based prospective cohort study among Inner Mongolians living in China. Participants were classified into four subgroups according to their drinking status and dyslipidemia. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curves were used to evaluate the association between alcohol drinking, dyslipidemia, and diabetes. During the follow-up period, 203 participants were found to have developed diabetes. The multivariable-adjusted odds ratios (95% confidence interval) for the incidence of non-dyslipidemia/drinkers, dyslipidemia/non-drinkers, and dyslipidemia/drinkers in diabetic patients were 1.40 (0.82-2.37), 1.73 (1.17-2.55), and 2.31 (1.38-3.87), respectively, when compared with non-dyslipidemia/non-drinkers. The area under the ROC curve for a model containing dyslipidemia and drinking status along with conventional factors (AUC=0.746) was significantly (P=0.003) larger than the one containing only conventional factors (AUC=0.711). The present study showed that dyslipidemia was an independent risk factor for diabetes, and that drinkers with dyslipidemia had the highest risk of diabetes in the Mongolian population. These findings suggest that dyslipidemia and drinking status may be valuable in predicting diabetes incidence. Copyright © 2016 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

The relationship between job stress and dyslipidemia.

PubMed

Catalina-Romero, C; Calvo, E; Sánchez-Chaparro, M A; Valdivielso, P; Sainz, J C; Cabrera, M; González-Quintela, A; Román, J

2013-03-01

To investigate whether there is an association between job stress, lipid profile and dyslipidemia diagnosis. This study used a questionnaire to evaluate job stress and lifestyle variables in 91,593 workers undergoing periodic checkups. Serum lipid levels were measured in all cases. The prevalence of job stress was 8.7% (95% CI, 8.5-8.8%). In bivariate analyses, job stress was significantly associated with previous dyslipidemia diagnosis (p < 0.001), lipid-lowering therapy (p < 0.001), and altered total-cholesterol (p = 0.001), HDL-cholesterol (p < 0.001) and LDL-cholesterol levels (p = 0.025). After adjusting for potential confounding variables, job stress was still associated with current dyslipidemia diagnosis (OR = 1.10; 95% CI, 1.04-1.17), high LDL-cholesterol (OR = 1.14; 95% CI, 1.05-1.23), low HDL-cholesterol (OR 1.08; 95% CI, 1.01-1.15), high total cholesterol/HDL-cholesterol ratio (OR 1.13; 95% CI, 1.05-1.23) and high LDL-cholesterol/HDL-cholesterol ratio (OR 1.11; 95% CI, 1.04-1.19). These results support the hypothesis of an association between job stress and lipid disturbances.

Prevalence of dyslipidemia among Iranian patients with idiopathic tinnitus.

PubMed

M-Shirazi, Minoo; Farhadi, Mohammad; Jalessi, Maryam; Kamrava, Seyyed-Kamran; Behzadi, Ashkan Heshmatzade; Arami, Behin

2011-07-01

Tinnitus is a sense of sound perception in absence of an external source which can affect life quality. Different conditions may lead to tinnitus including metabolic disorders such as dyslipidemia. The aim of this study was to investigate the prevalence of dyslipidemia among Iranian patients with idiopathic tinnitus. This was a cross-sectional study in which prevalence of dyslipidemia in fasting state and its subclasses were assessed in 1043 tinnitus patients aged 12-90 years who referred to Rasool Akram Hospital, Tehran, Iran, 2006-2009. Data was summarized by SPSS software version 17 and one sample t-test and Chi-Square test were applied to analyze the results. P less than 0.05 were considered significant. The most prevalent type of dyslipidemia was hypercholesterolemia with the frequency of 14.4% followed by low HDL-C with the frequency of 12.8%. Mean of total cholesterol, HDL-C, LDL-C and triglyceride levels in all patients were not greater than general population. Based on the results of the present study, there might be no need to check the serum lipid profile in tinnitus patients. We recommend further studies to assess both fasting and postprandial serum lipid profile in patients with idiopathic tinnitus. Simultaneous investigation of their dietary intake is also suggested.

Evaluation of Allele-Specific Somatic Changes of Genome-Wide Association Study Susceptibility Alleles in Human Colorectal Cancers

PubMed Central

Gerber, Madelyn M.; Hampel, Heather; Schulz, Nathan P.; Fernandez, Soledad; Wei, Lai; Zhou, Xiao-Ping; de la Chapelle, Albert; Toland, Amanda Ewart

2012-01-01

Background Tumors frequently exhibit loss of tumor suppressor genes or allelic gains of activated oncogenes. A significant proportion of cancer susceptibility loci in the mouse show somatic losses or gains consistent with the presence of a tumor susceptibility or resistance allele. Thus, allele-specific somatic gains or losses at loci may demarcate the presence of resistance or susceptibility alleles. The goal of this study was to determine if previously mapped susceptibility loci for colorectal cancer show evidence of allele-specific somatic events in colon tumors. Methods We performed quantitative genotyping of 16 single nucleotide polymorphisms (SNPs) showing statistically significant association with colorectal cancer in published genome-wide association studies (GWAS). We genotyped 194 paired normal and colorectal tumor DNA samples and 296 paired validation samples to investigate these SNPs for allele-specific somatic gains and losses. We combined analysis of our data with published data for seven of these SNPs. Results No statistically significant evidence for allele-specific somatic selection was observed for the tested polymorphisms in the discovery set. The rs6983267 variant, which has shown preferential loss of the non-risk T allele and relative gain of the risk G allele in previous studies, favored relative gain of the G allele in the combined discovery and validation samples (corrected p-value = 0.03). When we combined our data with published allele-specific imbalance data for this SNP, the G allele of rs6983267 showed statistically significant evidence of relative retention (p-value = 2.06×10−4). Conclusions Our results suggest that the majority of variants identified as colon cancer susceptibility alleles through GWAS do not exhibit somatic allele-specific imbalance in colon tumors. Our data confirm previously published results showing allele-specific imbalance for rs6983267. These results indicate that allele-specific imbalance of cancer

Dyslipidemia and Diabetic Retinopathy

PubMed Central

Chang, Yo-Chen; Wu, Wen-Chuan

2013-01-01

Diabetic retinopathy (DR) is one of the major microvascular complications of diabetes. In developed countries, it is the most common cause of preventable blindness in diabetic adults. Dyslipidemia, a major systemic disorder, is one of the most important risk factors for cardiovascular disease. Patients with diabetes have an increased risk of suffering from dyslipidemia concurrently. The aim of this article is to review the association between diabetic retinopathy (DR) and traditional/nontraditional lipid markers, possible mechanisms involving lipid metabolism and diabetic retinopathy, and the effect of lipid-lowering therapies on diabetic retinopathy. For traditional lipid markers, evidence is available that total cholesterol and low-density lipoprotein cholesterol are associated with the presence of hard exudates in patients with DR. The study of nontraditional lipid markers is advancing only in recently years. The severity of DR is inversely associated with apolipoprotein A1 (ApoA1), whereas ApoB and the ApoB-to-ApoA1 ratio are positively associated with DR. The role of lipid-lowering medication is to work as adjunctive therapy for better control of diabetes-related complications including DR. PMID:24380088

Factors influencing dyslipidemia in statin-treated patients in Lebanon and Jordan: results of the Dyslipidemia International Study.

PubMed

Azar, Sami T; Hantash, Hadi Abu; Jambart, Selim; El-Zaheri, Mohamed M; Rachoin, Rachoin; Chalfoun, Amal; Lahoud, Layla; Okkeh, Osama; Bramlage, Peter; Brudi, Philippe; Ambegaonkar, Baishali M

2014-01-01

Cardiovascular disease is the leading cause of death and disability worldwide. Therefore, as part of the Dyslipidemia International Study (DYSIS), we have analyzed the prevalence of lipid abnormalities and risk factors for dyslipidemia in statin-treated patients in Lebanon and Jordan. This cross-sectional, multicenter study enrolled 617 patients at 13 hospitals in Lebanon and Jordan. Patients were at least 45 years old and had been treated with statins for at least 3 months. Multivariate logistic regression analysis was used to determine patient characteristics contributing to dyslipidemia during statin therapy. Our findings indicated that 55.9% of statin-treated patients (mean age 60.3 years, 47% female) in Lebanon and Jordan did not achieve goal levels for low-density lipoprotein cholesterol which were dependent on Systematic Coronary Risk Evaluation (SCORE) risk, and 70% of patients (76% men and 63.3% of women) were at very high cardiovascular risk. Low-density lipoprotein cholesterol goals were not achieved in 67.2% of those with very high cardiovascular risk. The most commonly prescribed statin was atorvastatin (44.6%), followed by simvastatin (27.7%), rosuvastatin (21.2%), fluvastatin (3.3%), pravastatin (3%), and lovastatin (0.2%). Approximately half of the population was treated with a statin dose potency of 4, equaling 40 mg of simvastatin. In Lebanon and Jordan, the strongest independent associations with low-density lipoprotein cholesterol not at goal were current smoking (odds ratio [OR] 1.96; 95% confidence [CI] 1.25-3.08), diabetes mellitus (OR 2.53; 95% CI 1.70-3.77), and ischemic heart disease (OR 2.26; 95% CI 1.45-3.53), while alcohol consumption was associated with reduced risk (OR 0.12; 95% CI 0.03-0.57). We observed that many patients in Lebanon and Jordan experienced persistent dyslipidemia during statin treatment, supporting the notion that novel lipid-lowering strategies need to be developed. Also, social programs aimed at combating the

Diabetic Dyslipidemia Review: An Update on Current Concepts and Management Guidelines of Diabetic Dyslipidemia.

PubMed

Dake, Andrew W; Sora, Nicoleta D

2016-04-01

Cardiovascular disease is the most common cause of morbidity and mortality in patients with diabetes and the major source of cost in the care of diabetes. Treatment of dyslipidemia with cholesterol-lowering medications has been shown to decrease cardiovascular events. However, available guidelines for the treatment of dyslipidemia often contain significant differences in their recommendations. Lipid guidelines from National Cholesterol Education Program Adult Treatment Panel III, American Association of Clinical Endocrinologists, American Diabetes Association and American Heart Association/American College of Cardiology were reviewed. In addition a literature review was performed using PubMed to research diabetic peculiarities to the topic of lipids. Summarized within this article are the aforementioned, commonly-used guidelines as they relate to diabetes, as well as information regarding the diabetic phenotype of dislipidemia and the association between statins and new-onset diabetes. While the multitude of guidelines and the differences between them may contribute to confusion for practitioners, they are best viewed as tools to help tailor appropriate treatment plans for individual patients. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Serum IL-10, IL-17 and IL-23 levels as "bioumoral bridges" between dyslipidemia and atopy.

PubMed

Manti, S; Leonardi, S; Panasiti, I; Arrigo, T; Salpietro, C; Cuppari, C

2017-11-01

Although several studies suggest a possible link between dyslipidemia and atopy, literature findings are still unclear. The aim of the study was to investigate the relationship between dyslipidemia and atopy in a pediatric population affected by dyslipidemia or dyslipidemia/atopic predisposition. Children with dyslipidemia, dyslipidemia and atopy as well as healthy children were recruited. Serum total IgE, IL-10, IL-17, and IL-23 levels as well as fasting lipid values (total cholesterol, LDL, HDL and triglycerides) were performed on all enrolled children. The present study evaluated 23 patients affected by dyslipidemia, 26 patients affected by atopy and dyslipidemia and, 22healthy children. Serum total IgE levels significantly related also with serum cholesterol levels: positively with total cholesterol (p<0.05), LDL (p<0.05), and tryglicerides (p<0.001), but negatively with HDL (p<0.05). Serum levels of IL-10 were lower in children with atopy and dyslipidemia than patients with dyslipidemia (p<0.001). Serum IL-10 levels significantly related also with serum cholesterol levels: negatively with total cholesterol (p<0.001), LDL (p<0.05), and triglycerides (p<0.05), but positively with HDL (p<0.05). Serum IL-17 and IL-23 levels showed the same trend. They were significantly higher in children with atopy and dyslipidemia than patients with dyslipidemia (p<0.001). In particular, serum IL-17 and IL-23 values positively correlated with serum total IgE levels (p<0.05); serum total cholesterol levels (p<0.001); serum LDL levels (p<0.001); serum triglycerides levels (p<0.05). Although not statistically significant, an inverse correlation has been noted between serum IL-17, IL-23 and HDL levels. These findings support the notion that dyslipidemia and atopic predisposition share the same immune pathways as well as they offer new insights in the complex crosstalk between hyperlipidemia and atopy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Management of Dyslipidemia in Patients with Hypertension, Diabetes, and Metabolic Syndrome.

PubMed

Srikanth, Sundararajan; Deedwania, Prakash

2016-10-01

The purpose of this review is to discuss dyslipidemia in the various common clinical conditions including hypertension, diabetes mellitus, and metabolic syndrome and review the current therapeutic strategy in these settings. Dyslipidemias are common in patients with hypertension, diabetes mellitus, and metabolic syndrome. Epidemiologic studies have shown a strong correlation between serum lipid levels and risk of atherosclerotic cardiovascular disease. Multifactorial intervention strategies aimed at controlling lipids, blood pressure, and blood glucose simultaneously achieve maximal reductions in cardiovascular risk. Dyslipidemia and metabolic abnormalities are strongly associated with atherosclerosis and worse cardiovascular outcomes. While pharmacotherapy with statins has been proven to be beneficial for dyslipidemia, lifestyle modification emphasizing weight loss and regular exercise is an essential component of the interventional strategy. The common thread underlying atherosclerosis and metabolic abnormalities is endothelial dysfunction. Improved understanding of the role of endothelium in health and disease can potentially lead to novel therapies that may preempt development of atherosclerosis and its complications.

[Public sector participation in the supply of dyslipidemia medication in a population-based study].

PubMed

Petris, Airton José; Souza, Regina Kazue Tanno de; Bortoletto, Maira Sayuri Sakay

2016-12-01

The use of medications for the treatment of dyslipidemia is relevant in the control of cardiovascular disease. This article aims to analyze the prevalence, the use and the participation of the public sector in the supply of medication for adults aged 40 years and above using pharmacotherapy for dyslipidemia control living in a city in the southern region of Brazil. A cross-sectional, population-based study was conducted. Household interviews were staged with 1180 individuals aged over 40 living in Cambé, State of Paraná, of which 967 took laboratory examinations. The prevalence of dyslipidemia was 69.2%, of which 16.1% were taking medication. Among individuals undergoing treatment for dyslipidemia, 22.2% had adequate test results. Lipid-lowering medication used were simvastatin (81.5%) and bezafibrate (6.5%), mainly obtained by direct payment to private pharmacies and drug stores (52.2%) and NHS services (33.6%). A high prevalence of dyslipidemias was observed in population terms, together with a low level of dyslipidemia control and low participation of the public sector regarding the supply of medication compared to acquisition through direct payment for medication in private pharmacies. These results suggest a limited range of public policy for control of dyslipidemia.

Non-alcoholic fatty liver disease and dyslipidemia: An update.

PubMed

Katsiki, Niki; Mikhailidis, Dimitri P; Mantzoros, Christos S

2016-08-01

Non-alcoholic fatty liver (NAFLD) is the most common liver disease worldwide, progressing from simple steatosis to necroinflammation and fibrosis (leading to non-alcoholic steatohepatitis, NASH), and in some cases to cirrhosis and hepatocellular carcinoma. Inflammation, oxidative stress and insulin resistance are involved in NAFLD development and progression. NAFLD has been associated with several cardiovascular (CV) risk factors including obesity, dyslipidemia, hyperglycemia, hypertension and smoking. NAFLD is also characterized by atherogenic dyslipidemia, postprandial lipemia and high-density lipoprotein (HDL) dysfunction. Most importantly, NAFLD patients have an increased risk for both liver and CV disease (CVD) morbidity and mortality. In this narrative review, the associations between NAFLD, dyslipidemia and vascular disease in NAFLD patients are discussed. NAFLD treatment is also reviewed with a focus on lipid-lowering drugs. Finally, future perspectives in terms of both NAFLD diagnostic biomarkers and therapeutic targets are considered. Copyright © 2016 Elsevier Inc. All rights reserved.

Identification of novel alleles of the rice blast resistance gene Pi54

NASA Astrophysics Data System (ADS)

Vasudevan, Kumar; Gruissem, Wilhelm; Bhullar, Navreet K.

2015-10-01

Rice blast is one of the most devastating rice diseases and continuous resistance breeding is required to control the disease. The rice blast resistance gene Pi54 initially identified in an Indian cultivar confers broad-spectrum resistance in India. We explored the allelic diversity of the Pi54 gene among 885 Indian rice genotypes that were found resistant in our screening against field mixture of naturally existing M. oryzae strains as well as against five unique strains. These genotypes are also annotated as rice blast resistant in the International Rice Genebank database. Sequence-based allele mining was used to amplify and clone the Pi54 allelic variants. Nine new alleles of Pi54 were identified based on the nucleotide sequence comparison to the Pi54 reference sequence as well as to already known Pi54 alleles. DNA sequence analysis of the newly identified Pi54 alleles revealed several single polymorphic sites, three double deletions and an eight base pair deletion. A SNP-rich region was found between a tyrosine kinase phosphorylation site and the nucleotide binding site (NBS) domain. Together, the newly identified Pi54 alleles expand the allelic series and are candidates for rice blast resistance breeding programs.

Epidemiological Survey of Dyslipidemia in Civil Aviators in China from 2006 to 2011

PubMed Central

Zhao, Rongfu; Xiao, Dan; Fan, Xiaoying; Ge, Zesong; Wang, Linsheng; Yan, Tiecheng; Wang, Jianzhi; Wei, Qixin; Zhao, Yan

2014-01-01

Aim. This study aimed to analyze blood lipid levels, temporal trend, and age distribution of dyslipidemia in civil aviators in China. Methods. The 305 Chinese aviators were selected randomly and followed up from 2006 to 2011. Their total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were evaluated annually. Mean values for each parameter by year were compared using a linear mixed-effects model. The temporal trend of borderline high, high, and low status for each index and of overall borderline high, hyperlipidemia, and dyslipidemia by year was tested using a generalized linear mixed model. Results. The aviators' TC (F = 4.33, P < 0.01), HDL-C (F = 23.25, P < 0.01), and LDL-C (F = 6.13, P < 0.01) values differed across years. The prevalence of dyslipidemia (F = 5.53, P < 0.01), borderline high (F = 6.52, P < 0.01), and hyperlipidemia (F = 3.90, P < 0.01) also differed across years. The prevalence rates for hyperlipidemia and dyslipidemia were the highest in the 41–50-year-old and 31–40-year-old groups. Conclusions. Civil aviators in China were in high dyslipidemia and borderline high level and presented with dyslipidemia younger than other Chinese populations. PMID:24693285

Prevalence of dyslipidemia among Iranian patients with idiopathic tinnitus

PubMed Central

M-Shirazi, Minoo; Farhadi, Mohammad; Jalessi, Maryam; Kamrava, Seyyed-Kamran; Behzadi, Ashkan Heshmatzade; Arami, Behin

2011-01-01

BACKGROUND: Tinnitus is a sense of sound perception in absence of an external source which can affect life quality. Different conditions may lead to tinnitus including metabolic disorders such as dyslipidemia. The aim of this study was to investigate the prevalence of dyslipidemia among Iranian patients with idiopathic tinnitus. METHODS: This was a cross-sectional study in which prevalence of dyslipidemia in fasting state and its subclasses were assessed in 1043 tinnitus patients aged 12-90 years who referred to Rasool Akram Hospital, Tehran, Iran, 2006-2009. Data was summarized by SPSS software version 17 and one sample t-test and Chi-Square test were applied to analyze the results. P less than 0.05 were considered significant. RESULTS: The most prevalent type of dyslipidemia was hypercholesterolemia with the frequency of 14.4% followed by low HDL-C with the frequency of 12.8%. Mean of total cholesterol, HDL-C, LDL-C and triglyceride levels in all patients were not greater than general population. CONCLUSIONS: Based on the results of the present study, there might be no need to check the serum lipid profile in tinnitus patients. We recommend further studies to assess both fasting and postprandial serum lipid profile in patients with idiopathic tinnitus. Simultaneous investigation of their dietary intake is also suggested. PMID:22279456

The Impact of Cardiorespiratory Fitness Levels on the Risk of Developing Atherogenic Dyslipidemia.

PubMed

Breneman, Charity B; Polinski, Kristen; Sarzynski, Mark A; Lavie, Carl J; Kokkinos, Peter F; Ahmed, Ali; Sui, Xuemei

2016-10-01

Low cardiorespiratory fitness has been established as a risk factor for cardiovascular-related morbidity. However, research about the impact of fitness on lipid abnormalities, including atherogenic dyslipidemia, has produced mixed results. The purpose of this investigation is to examine the influence of baseline fitness and changes in fitness on the development of atherogenic dyslipidemia. All participants completed at least 3 comprehensive medical examinations performed by a physician that included a maximal treadmill test between 1976 and 2006 at the Cooper Clinic in Dallas, Texas. Atherogenic dyslipidemia was defined as a triad of lipid abnormalities: low high-density-lipoprotein cholesterol ([HDL-C] <40 mg/dL), high triglycerides ([TGs] ≥200 mg/dL), and high low-density-lipoprotein cholesterol ([LDL-C] ≥160 mg/dL). A total of 193 participants developed atherogenic dyslipidemia during an average of 8.85 years of follow-up. High baseline fitness was protective against the development of atherogenic dyslipidemia in comparison with those with low fitness (odds ratio [OR] 0.57; 95% confidence interval [CI], 0.37-0.89); however, this relationship became nonsignificant after controlling for baseline HDL-C, LDL-C, and TG levels. Participants who maintained fitness over time had lower odds of developing atherogenic dyslipidemia than those with a reduction in fitness (OR 0.56; 95% CI, 0.34-0.91) after adjusting for baseline confounders and changes in known risk factors. High fitness at baseline and maintenance of fitness over time are protective against the development of atherogenic dyslipidemia. Copyright © 2016 Elsevier Inc. All rights reserved.

Medications not intended for treatment of dyslipidemias and with a variable effect on lipids.

PubMed

Whayne, Thomas F; Mukherjee, Debabrata

2014-01-01

Many therapeutically active medications have significant side effects, some of which can compromise the intended therapeutic goal. The development of plasma lipid abnormalities or a dyslipidemia as the result of a medication intended for an unrelated effect has been reported. Human immunodeficiency virus (HIV) infection can cause dyslipidemia as can the medications used to treat this infection. Such dyslipidemia can be a significant problem made more relevant by the already increased risk of cardiovascular (CV) disease faced by these patients. Some hypoglycemic medications used to treat diabetes can also be associated with dyslipidemia, most notably rosiglitazone. Antihypertensive medications are intended to decrease CV risk but are not free of dyslipidemia problems with thiazides able to cause hypertriglyceridemia and older beta-blockers without an alpha-blocking effect associated with moderate plasma lipid abnormalities and altered glucose metabolism. Estrogen administered orally can be associated with a severe hypertriglyceridemia. Currently-used antipsychotic medications have a significant association with hypertriglyceridemia. Clinicians must be aware of the dyslipidemias caused by these medications and know how to manage them, even treating a secondary dyslipidemia with another medication as in the case of HIV infection rather than trying to switch treatment of the infection in many cases. Mention is also made of lipid lowering effects of medications intended for other purposes (e.g. angiotensin receptor blockers and orlistat).

The prevalence of dyslipidemia and associated factors in children and adolescents with type 1 diabetes.

PubMed

Bulut, Tuba; Demirel, Fatma; Metin, Ayşe

2017-02-01

Dyslipidemia increases the frequency and severity of micro and macrovascular complications of type 1 diabetes (T1D). The present study aims to determine the prevalence of dyslipidemia and its association with clinical and laboratory findings in diabetic children and adolescents. The study included 202 children and adolescents with T1D. Demographic data and laboratory findings were obtained from patients files. Dyslipidemia prevalence was found to be 26.2%. Hypercholesterolemia (15.8%) and hyperglyceridemia (12.9%) were most common findings. Age, body mass index (BMI), hemoglobin A1c (A1C) and poor metabolic control were significantly higher in cases with dyslipidemia. Smoking rate was 14.1% in the pubertal group. Poor metabolic control and dyslipidemia was found higher among smokers (p<0.05). Blood lipid levels should be monitored regularly and nutrition education should be repeated periodically to prevent and control dyslipidemia in patients with T1D. Smoking-related risks should be a part of patient education in the pubertal period.

Dyslipidemia and associated risk factors in a resettlement colony of Delhi.

PubMed

Sharma, Urvi; Kishore, Jugal; Garg, Ankur; Anand, Tanu; Chakraborty, Montosh; Lali, Pramod

2013-01-01

Cardiovascular diseases are a major cause of morbidity and mortality in India, with dyslipidemia contributing significantly to the risk. There are few community-based studies that highlight the burden and risk factors associated with dyslipidemia in the Indian population. To determine the prevalence and risk factors associated with dyslipidemia among adults ages 18 years and older in a resettlement colony located in central Delhi. A cross-sectional study that included a random sample of 200 adults was designed. A study tool based on the World Health Organization STEPwise approach to surveillance of noncommunicable diseases and their risk factors (STEPS) questionnaire was used. Fasting venous blood sample was collected to assess the lipid profile and anthropometric measures of the participants were recorded. Criteria based on the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults were used to define the cut offs for dyslipidemia. Data were analyzed with the Statistical Package for Social Sciences, version 17. Of a total of 200 study subjects, 34% had increased total cholesterol levels (≥200 mg %), 38% had increased low-density lipoprotein levels (≥130 mg %), 40% had increased triglyceride levels (≥150 mg %), and 42% had low high-density lipoprotein levels (<40 mg %). Using the logistic regression model, we found age, hypertension, alcohol consumption, and abdominal obesity to be associated with increased odds of dyslipidemia. A high proportion of individuals in the community have dyslipidemia, often associated with modifiable risk factors. The situation demands programs aimed at risk factor reduction. A focus on behavior change and health promotion targeting the younger age group is recommended. Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Independent Association between Sleep Fragmentation and Dyslipidemia in Patients with Obstructive Sleep Apnea.

PubMed

Qian, Yingjun; Yi, Hongliang; Zou, Jianyin; Meng, Lili; Tang, Xulan; Zhu, Huaming; Yu, Dongzhen; Zhou, Huiqun; Su, Kaiming; Guan, Jian; Yin, Shankai

2016-05-17

Obstructive sleep apnea (OSA) is independently associated with dyslipidemia. Previous studies have demonstrated that sleep fragmentation can impair lipid metabolism. The present study aimed to identify whether sleep fragmentation is independently associated with dyslipidemia, in a large-scale, clinic-based consecutive OSA sample. This cross-sectional study was conducted among 2,686 patients who underwent polysomnography (PSG) for suspicion of OSA from January 2008 to January 2013 at the sleep laboratory. Multivariate regression analyses were performed to evaluate the independent associations between the microarousal index (MAI) and lipid profiles adjusting for potential confounders, including metabolic syndrome components and nocturnal intermittent hypoxia. The adjusted odds ratios (ORs) for various types of dyslipidemia according to MAI quartiles, as determined by logistic regression were also evaluated. MAI was found positively associated with low-density lipoprotein cholesterol (LDL-c) but not with total cholesterol (TC), triglyceride (TG) or high-density lipoprotein cholesterol (HDL-c). Furthermore, the adjusted ORs (95% confidence interval) for hyper-LDL cholesterolemia increased across MAI quartiles, as follows: 1 (reference), 1.3 (1.1-1.7), 1.6 (1.2-2.0), and 1.6 (1.2-2.1) (p = 0.001, linear trend). Sleep fragmentation in OSA is independently associated with hyper-LDL cholesterolemia, which may predispose patients with OSA to a higher risk of cardiovascular disease.

Diversity of alleles encoding HLA-B40: relative frequencies in united states populations and description of five novel alleles.

PubMed

Pimtanothai, N; Rizzuto, G A; Slack, R; Steiner, N K; Kosman, C A; Jones, P F; Koester, R; Ng, J; Hartzman, R J; Katovich Hurley, C

2000-08-01

The frequency of each B*40 allele was determined by DNA sequencing in four major United States populations: Caucasians, African Americans, Asians/Pacific Islanders, and Hispanics. Thirty-two individuals from each ethnic group, who were previously described serologically as B40, B60, or B61, were randomly selected out of a pool of 82,979 unrelated individuals for allele characterization. Out of nine different B*40 alleles identified in this study, B*4001 and B*4002 were the two most frequent B*40 alleles in all the population groups. B*4001 was the primary B*40 allele seen in Caucasians (83%) and African Americans (76%), while B*4002 was found in the majority of Hispanics (62%). The distributions of both alleles were comparable in the Asian/Pacific Islander population. These two alleles were the only B*40 alleles detected in Caucasians while four to five additional B*40 alleles were seen in the other population groups. The other B*40 alleles detected in this study included: B*4003 and B*4010 in Asian/Pacific Islanders; B*4012 and B*4016 in African Americans; and B*4004, B*4006, and B*4027 in Hispanics. Analysis revealed significant differences between Hispanics and all other groups as well as between African Americans and Asian/Pacific Islanders. This report also describes five novel B*40 alleles: B*4019, B*4020, B*4024, B*4027, and B*4028.

Molecular analyses of the agouti allele in the Japanese house mouse identify a novel variant of the agouti gene.

PubMed

Iwasa, Masahiro A; Kawamura, Sayaka; Myoshu, Hikari; Suzuki, Taichi A

2018-03-01

It has been thought that the Japanese house mouse carries the A w allele at the agouti locus causing light-colored bellies, but they do not always show this coloration. Thus, the presence of the A w allele seems to be doubtful in them. To ascertain whether the A w allele is present, a two-pronged approach was used. First, we compared lengths of DNA fragments obtained from three PCRs conducted on them to the known fragment sizes generated from mouse strains exhibiting homozygosities of either a/a, A/A, or A w /A w . PCR I, PCR II, and PCR III amplify only in the A and A w alleles, the a and A w alleles, and the a allele, respectively, and we detected amplifications in strains with A/A and A w /A w by PCR I, in those with a/a and the Japanese house mouse by PCR II, and in those with a/a by PCR III. Second, we sequenced the exon 1A region of the agouti gene and obtained sequences corresponding to the above strains and the Japanese house mouse, but their sequences were similar to those of the a allele. We concluded that their agouti allele is not identical to the A w allele and seems to be a novel type similar to the a allele.

Factors influencing dyslipidemia in statin-treated patients in Lebanon and Jordan: results of the Dyslipidemia International Study

PubMed Central

Azar, Sami T; Hantash, Hadi Abu; Jambart, Selim; El-Zaheri, Mohamed M; Rachoin, Rachoin; Chalfoun, Amal; Lahoud, Layla; Okkeh, Osama; Bramlage, Peter; Brudi, Philippe; Ambegaonkar, Baishali M

2014-01-01

Background Cardiovascular disease is the leading cause of death and disability worldwide. Therefore, as part of the Dyslipidemia International Study (DYSIS), we have analyzed the prevalence of lipid abnormalities and risk factors for dyslipidemia in statin-treated patients in Lebanon and Jordan. Methods This cross-sectional, multicenter study enrolled 617 patients at 13 hospitals in Lebanon and Jordan. Patients were at least 45 years old and had been treated with statins for at least 3 months. Multivariate logistic regression analysis was used to determine patient characteristics contributing to dyslipidemia during statin therapy. Results Our findings indicated that 55.9% of statin-treated patients (mean age 60.3 years, 47% female) in Lebanon and Jordan did not achieve goal levels for low-density lipoprotein cholesterol which were dependent on Systematic Coronary Risk Evaluation (SCORE) risk, and 70% of patients (76% men and 63.3% of women) were at very high cardiovascular risk. Low-density lipoprotein cholesterol goals were not achieved in 67.2% of those with very high cardiovascular risk. The most commonly prescribed statin was atorvastatin (44.6%), followed by simvastatin (27.7%), rosuvastatin (21.2%), fluvastatin (3.3%), pravastatin (3%), and lovastatin (0.2%). Approximately half of the population was treated with a statin dose potency of 4, equaling 40 mg of simvastatin. In Lebanon and Jordan, the strongest independent associations with low-density lipoprotein cholesterol not at goal were current smoking (odds ratio [OR] 1.96; 95% confidence [CI] 1.25–3.08), diabetes mellitus (OR 2.53; 95% CI 1.70–3.77), and ischemic heart disease (OR 2.26; 95% CI 1.45–3.53), while alcohol consumption was associated with reduced risk (OR 0.12; 95% CI 0.03–0.57). Conclusion We observed that many patients in Lebanon and Jordan experienced persistent dyslipidemia during statin treatment, supporting the notion that novel lipid-lowering strategies need to be developed. Also

Obstructive sleep apnea combined dyslipidemia render additive effect on increasing atherosclerotic cardiovascular diseases prevalence.

PubMed

Cao, Zhiyong; Zhang, Ping; He, Zhiqing; Yang, Jing; Liang, Chun; Ren, Yusheng; Wu, Zonggui

2016-05-26

Current study was designed to investigate the effects of obstructive sleep apnea (OSA) combined dyslipidemia on the prevalence of atherosclerotic cardiovascular diseases (ASCVD). This was a cross-sectional study and subjects with documented dyslipidemia and without previous diagnosis of OSA were enrolled. Polysomnography was applied to evaluate apnea-hypopnea index (AHI). Based on AHI value, subjects were classified into four groups: without OSA, mild, moderate and severe OSA groups. Clinical characteristics and laboratory examination data were recorded. Relationship between AHI event and lipid profiles was analyzed, and logistic regression analysis was used to evaluate the effects of OSA combined dyslipidemia on ASCVD prevalence. Totally 248 subjects with dyslipidemia were enrolled. Compared to the other 3 groups, subjects with severe OSA were older, male predominant and had higher smoking rate. In addition, subjects with severe OSA had higher body mass index, waist-hip ratio, blood pressure, and higher rates of overweight and obesity. Serum levels of fasting plasma glucose, glycated hemoglobin, LDL-C and CRP were all significantly higher. ASCVD prevalence was considerably higher in subjects with severe OSA. AHI event in the severe OSA group was up to 35.4 ± 5.1 events per hour which was significantly higher than the other groups (P < 0.05 for trend). Pearson correlation analysis showed that only LDL-C was positively correlated with AHI events (r = 0.685, P < 0.05). Logistic regression analysis revealed that in unadjusted model, compared to dyslipidemia plus no-OSA group (reference group), OSA enhanced ASCVD risk in subjects with dyslipidemia, regardless of OSA severity. After extensively adjusted for confounding variables, the odds of dyslipidemia plus mild-OSA was reduced to insignificance. While the effects of moderate- and severe-OSA on promoting ASCVD risk in subjects with dyslipidemia remained significant, with severe-OSA most prominent (odds ratio: 1

Supplementation with Watermelon Extract Reduces Total Cholesterol and LDL Cholesterol in Adults with Dyslipidemia under the Influence of the MTHFR C677T Polymorphism.

PubMed

Massa, Nayara M L; Silva, Alexandre S; de Oliveira, Caio V C; Costa, Maria J C; Persuhn, Darlene C; Barbosa, Carlos V S; Gonçalves, Maria da C R

2016-08-01

Dyslipidemia and genetic polymorphisms are associated with increased risk for developing cardiovascular diseases, and watermelon appears to have the potential to improve hyperlipidemia due to the presence of nutrients such as arginine and citrulline. To test the hypolipidemic effect of watermelon extract (Citrullus lanatus) and the influence of the methylenetetrahydrofolate reductase genotype (MTHFR C677T) on supplementation response. This is an experimental clinical phase II randomized and double-blind study. Forty-three subjects with dyslipidemia were randomly divided into 2 groups: experimental (n = 22) and control (n = 21) groups. The subjects were supplemented daily for 42 days with 6 g of watermelon extract or a mixture of carbohydrates (sucrose/glucose/fructose). The use of watermelon extract reduced plasma total cholesterol (p < 0.05) and low-density lipoprotein (p < 0.01) without modifying triglycerides, high-density lipoprotein, and very low-density lipoprotein values. Only carriers of the T allele (MTHFR C677T) showed decreasing concentrations of low-density lipoprotein (p < 0.01). No changes in anthropometric parameters analyzed were observed. This is the first study to demonstrate the beneficial effect of the consumption of watermelon extract in reducing plasma levels of lipids in humans. The MTHFR C677T polymorphism did not affect the plasma lipid concentration but made individuals more responsive to treatment with watermelon. The consumption of this functional food represents an alternative therapy in the combined treatment of patients with dyslipidemia, promoting health and minimizing the development of risk factors for cardiovascular diseases.

Auto-inhibitory regulation of angiotensin II functionality in hamster aorta during the early phases of dyslipidemia.

PubMed

Pereira, Priscila Cristina; Pernomian, Larissa; Côco, Hariane; Gomes, Mayara Santos; Franco, João José; Marchi, Kátia Colombo; Hipólito, Ulisses Vilela; Uyemura, Sergio Akira; Tirapelli, Carlos Renato; de Oliveira, Ana Maria

2016-06-15

Emerging data point the crosstalk between dyslipidemia and renin-angiotensin system (RAS). Advanced dyslipidemia is described to induce RAS activation in the vasculature. However, the interplay between early dyslipidemia and the RAS remains unexplored. Knowing that hamsters and humans have a similar lipid profile, we investigated the effects of early and advanced dyslipidemia on angiotensin II-induced contraction. Cumulative concentration-response curves for angiotensin II (1.0pmol/l to 1.0µmol/l) were obtained in the hamster thoracic aorta. We also investigated the modulatory action of NAD(P)H oxidase on angiotensin II-induced contraction using ML171 (Nox-1 inhibitor, 0.5µmol/l) and VAS2870 (Nox-4 inhibitor, 5µmol/l). Early dyslipidemia was detected in hamsters treated with a cholesterol-rich diet for 15 days. Early dyslipidemia decreased the contraction induced by angiotensin II and the concentration of Nox-4-derived hydrogen peroxide. Advanced dyslipidemia, observed in hamsters treated with cholesterol-rich diet for 30 days, restored the contractile response induced by angiotensin II by compensatory mechanism that involves Nox-4-mediated oxidative stress. The hyporresponsiveness to angiotensin II may be an auto-inhibitory regulation of the angiotensinergic function during early dyslipidemia in an attempt to reduce the effects of the upregulation of the vascular RAS during the advanced stages of atherogenesis. The recovery of vascular angiotensin II functionality during the advanced phases of dyslipidemia is the result of the upregulation of redox-pro-inflammatory pathway that might be most likely involved in atherogenesis progression rather than in the recovery of vascular function. Taken together, our findings show the early phase of dyslipidemia may be the most favorable moment for effective atheroprotective therapeutic interventions. Copyright © 2016 Elsevier B.V. All rights reserved.

Identifying the Deleterious Effect of Rare LHX4 Allelic Variants, a Challenging Issue

PubMed Central

Rochette, Claire; Jullien, Nicolas; Saveanu, Alexandru; Caldagues, Emmanuelle; Bergada, Ignacio; Braslavsky, Debora; Pfeifer, Marija; Reynaud, Rachel; Herman, Jean-Paul; Barlier, Anne; Brue, Thierry; Enjalbert, Alain; Castinetti, Frederic

2015-01-01

LHX4 is a LIM homeodomain transcription factor involved in the early steps of pituitary ontogenesis. To date, 8 heterozygous LHX4 mutations have been reported as responsible of combined pituitary hormone deficiency (CPHD) in Humans. We identified 4 new LHX4 heterozygous allelic variants in patients with congenital hypopituitarism: W204X, delK242, N271S and Q346R. Our objective was to determine the role of LHX4 variants in patients’ phenotypes. Heterologous HEK293T cells were transfected with plasmids encoding for wild-type or mutant LHX4. Protein expression was analysed by Western Blot, and DNA binding by electro-mobility shift assay experiments. Target promoters of LHX4 were cotransfected with wild type or mutant LHX4 to test the transactivating abilities of each variant. Our results show that the W204X mutation was associated with early GH and TSH deficiencies and later onset ACTH deficiency. It led to a truncated protein unable to bind to alpha-Gsu promoter binding consensus sequence. W204X was not able to activate target promoters in vitro. Cotransfection experiments did not favour a dominant negative effect. In contrast, all other mutants were able to bind the promoters and led to an activation similar as that observed with wild type LHX4, suggesting that they were likely polymorphisms. To conclude, our study underlines the need for functional in vitro studies to ascertain the role of rare allelic variants of LHX4 in disease phenotypes. It supports the causative role of the W204X mutation in CPHD and adds up childhood onset ACTH deficiency to the clinical spectrum of the various phenotypes related to LHX4 mutations. PMID:25955177

Prevalence, awareness, treatment and control of dyslipidemia among adults in Northwestern China: the cardiovascular risk survey

PubMed Central

2014-01-01

Aim The aim of this study was to estimate the prevalence, awareness, treatment, and control of dyslipidemia in Xinjiang, China. Method Stratified sampling method was used to select a representative sample of the general population including Chinese Han, Uygur, and Kazak in this geographic area. Seven cities were chosen. Based on the government records of registered residences, one participant was randomly selected from each household. The eligibility criterion for the study was ≥ 35 years of age. Results A total of 14,618 participants (5,757 Han, 4,767 Uygur, and 4,094 Kazak), were randomly selected from 26 villages in 7 cities. The prevalence of dyslipidemia was 52.72% in the all participants. The prevalence of dyslipidemia was higher in Han than that in the other two ethnic (58.58% in Han, 48.27% in Uygur, and 49.60% in Kazak, P < 0.000). The prevalence of dyslipidemia was higher in men than that in women (56.4% vs. 49.3%, P < 0.000). Among the participants with dyslipidemia, the proportion of those who aware, treat, control of dyslipidemia were 53.67%, 22.51%, 17.09% in Han, 42.19%, 27.78%, 16.20% in Uygur, 37.02%, 21.11%, 17.77% in Kazak. Conclusion Dyslipidemia is highly prevalent in Xinjiang. The proportion of participants with dyslipidemia who were aware, treated, and controlled is unacceptably low. These results underscore the urgent need to develop national strategies to improve the prevention, detection, and treatment of dyslipidemia in Xinjiang. PMID:24393232

[Guidelines for the management of dyslipidemia].

PubMed

Díaz Rodríguez, Ángel

2014-09-01

The AHA/ACC 2013 guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease (ASCVD) in adults contains major differences with the previous ESC/EAS 2011 guidelines and the remaining international guidelines, which has generated major controversies. The AHA/ACC document has developed a new model for estimating cardiovascular risk for primary prevention which is not comparable with the SCORE recommended in the European guidelines. This guideline does not establish a fixed target for low-density lipoprotein cholesterol (LDLc). Instead, it identifies 4 major statin benefit groups at risk for the development ASCVD, who should receive low-, moderate-, and high-intensity statin therapy to reduce LCLc. In contrast, the European guidelines maintain LDLc as the main treatment target and non-high-density lipoprotein cholesterol as a secondary treatment target. The document recommends calculating cardiovascular risk for the overall treatment of patients with dyslipidemia according to 4 risk levels (low, moderate, high, and very high), establishes LDLc treatment targets, and recommends a statin-based therapeutic strategy and other, lipid-lowering strategies, aimed at achieving these targets. The American guidelines cannot be extrapolated to the European population. Target-based treatment, as recommended in the EAS/ESC guidelines, is the best strategy for Europe. In Spain, the Primary Care Guidelines of the Spanish Society of Family and Community Medicine (semFYC) and the Spanish Society of Primary Care Physicians (SEMERGEN) are based on the European recommendations. Finally, the Spanish Society of Arteriosclerosis (SEA), SEMERGEN, semFYC and the Spanish Society of General Medicine (SEMG) are reaching a consensus on the approach and management of patients with atherogenic dyslipidemia in primary care. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Medicina Rural y Generalista (SEMERGEN). All rights reserved.

[Clinical practice guideline. Diagnosis and treatment of dyslipidemia.

PubMed

Canalizo-Miranda, Elvia; Favela-Pérez, Eddie Alberto; Salas-Anaya, Javier Alejandro; Gómez-Díaz, Rita; Jara-Espino, Ricardo; Del Pilar Torres-Arreola, Laura; Viniegra-Osorio, Arturo

2013-01-01

Non-communicable diseases are a public health problem in México. Coronary heart disease and diabetes mellitus are the first and second cause of death in the country, followed by thrombotic cerebrovascular events. Cardiovascular diseases are the leading cause of death; one primary risk factor is hypercholesterolemia. The detection and treatment of lipid abnormalities is the key to the prevention and management of chronic non-communicable diseases. Two nationally representative surveys have shown that lipid abnormalities are the most common risk factors in Mexican adults. The purpose of this guide is to provide a basis for identifying dyslipidemia in a timely manner, and to systematize the criteria for diagnosis and treatment in the first and second level of care.

[A study on the epidemic characteristics of dyslipidemia in adults of nine provinces of China].

PubMed

Dai, J; Min, J Q; Yang, Y J

2018-02-24

Objective: To explore the current prevalence of dyslipidemia in adult population of 9 provinces of China and the epidemic characteristics of this disease. The potential influence of social economic development on dyslipidemia was also observed. Methods: Present research data are derived from the result of the investigation about survey on health and nutrition in China in 2011, in which multistage stratified cluster random sampling method was adopted to investigate the 24 345 individuals in 216 communities from 9 provinces in China and 10 242 blood samples were collected. In this research, 8 669 blood samples of people over 18 years old were selected for final analysis. After adjustment of age, the percentage of dyslipidemia patients in Chinese adults was calculated. Results: The percentage of dyslipidemia in Chinese adults is 39.91% (3 460/8 669). The percentage of dyslipidemia at the age of 18-24, 35-44, 45-59 and over 60 years old were 30.25% (373/1 233),37.19% (774/2 081), 44.22% (1 304/2 949) and 41.94%(1 009/2 406),respectively (χ(2)=333.02, P< 0.01); the percentage of dyslipidemia in male and female population was 51.11% (1 956/3 827) and 31.06%(1 504/4 842), respectively (χ(2)=60.35, P< 0.01); the percentage of dyslipidemia in urban residents and rural residents was 42.56% (1 144/2 687) and 38.72%(2 316/5 982), respectively (χ(2)=11.72, P< 0.01);the percentage of dyslipidemia in high-GDP regions and low-GDP regions was 43.04% (1 567/3 641) and 37.65% (1 893/5 028), respectively (χ(2)=25.57, P< 0.01) .The prevalence of adult hypercholesterolemia in Chinese adult is 9.01% (781/8 669), the prevalence of borderline increased cholesterol is 22.54% (1 954/8 669), the prevalence of hypertriglyceridemia is 27.02% (2 342/8 669), the prevalence of lower high-density lipoproteinemia is 14.36% (1 245/8 669) and the prevalence of increased low-density lipoproteinemia was 10.23% (887/8 669). All prevalence rates are significantly higher compared to the 2005 survey

Anthropometric and metabolic indices in assessment of type and severity of dyslipidemia.

PubMed

Zaid, Muhammad; Ameer, Fatima; Munir, Rimsha; Rashid, Rida; Farooq, Nimrah; Hasnain, Shahida; Zaidi, Nousheen

2017-02-28

It has been shown that obesity is associated with increased rates of dyslipidemia. The present work revisits the association between plasma lipid levels and classical indicators of obesity including body mass index (BMI). The significance of various anthropometric/metabolic variables in clinical assessment of type and severity of dyslipidemia was also determined. Recently described body indices, a body shape index (ABSI) and body roundness index (BRI), were also assessed in this context. For the present cross-sectional analytical study, the participants (n = 275) were recruited from the patients visiting different health camps. Participants were anthropometrically measured and interviewed, and their fasting intravenous blood was collected. Plasma lipid levels were accordingly determined. The values for different anthropometric parameters are significantly different between dyslipidemic and non-dyslipidemic participants. Receiver operating characteristics curve analyses revealed that all the tested variables gave the highest area under the curve (AUC) values for predicting hypertriglyceridemia in comparison to other plasma lipid abnormalities. BRI gave slightly higher AUC values in predicting different forms of dyslipidemia in comparison to BMI, whereas ABSI gave very low values. Several anthropometric/metabolic indices display increased predictive capabilities for detecting hypertriglyceridemia in comparison to any other form of plasma lipid disorders. The capacity of BRI to predict dyslipidemia was comparable but not superior to the classical indicators of obesity, whereas ABSI could not detect dyslipidemia.

Predictive capacity of anthropometric indicators for dyslipidemia screening in children and adolescents.

PubMed

Quadros, Teresa Maria Bianchini; Gordia, Alex Pinheiro; Silva, Rosane Carla Rosendo; Silva, Luciana Rodrigues

2015-01-01

To analyze the predictive capacity of anthropometric indicators and their cut-off values for dyslipidemia screening in children and adolescents. This was a cross-sectional study involving 1139 children and adolescents, of both sexes, aged 6-18 years. Body weight, height, waist circumference, subscapular, and triceps skinfold thickness were measured. The body mass index and waist-to-height ratio were calculated. Children and adolescents exhibiting at least one of the following lipid alterations were defined as having dyslipidemia: elevated total cholesterol, low high-density lipoprotein, elevated low-density lipoprotein, and high triglyceride concentration. A receiver operating characteristic curve was constructed and the area under the curve, sensitivity, and specificity was calculated for the parameters analyzed. The prevalence of dyslipidemia was 62.1%. The waist-to-height ratio, waist circumference, subscapular, body mass index, and triceps skinfold thickness, in this order, presented the largest number of significant accuracies, ranging from 0.59 to 0.78. The associations of the anthropometric indicators with dyslipidemia were stronger among adolescents than among children. Significant differences between accuracies of the anthropometric indicators were only observed by the end of adolescence; the accuracy of waist-to-height ratio was higher than that of subscapular (p=0.048) for females, and the accuracy of waist circumference was higher than that of subscapular (p=0.029) and body mass index (p=0.012) for males. In general, the cut-off values of the anthropometric predictors of dyslipidemia increased with age, except for waist-to-height ratio. Sensitivity and specificity varied substantially between anthropometric indicators, ranging from 75.6 to 53.5 and from 75.0 to 50.0, respectively. The anthropometric indicators studied had little utility as screening tools for dyslipidemia, especially in children. Copyright © 2015 Sociedade Brasileira de Pediatria

Dyslipidemia and Diabetes Increase the OPG/TRAIL Ratio in the Cardiovascular System.

PubMed

Toffoli, Barbara; Fabris, Bruno; Bartelloni, Giacomo; Bossi, Fleur; Bernardi, Stella

2016-01-01

Background . Dyslipidemia and diabetes are two of the most well established risk factors for the development of cardiovascular disease (CVD). Both of them usually activate a complex range of pathogenic pathways leading to organ damage. Here we hypothesized that dyslipidemia and diabetes could affect osteoprotegerin (OPG) and TNF-related apoptosis-inducing ligand (TRAIL) expression in the vessels and the heart. Materials and Methods . Gene and protein expression of OPG, TRAIL, and OPG/TRAIL ratio were quantified in the aorta and the hearts of control mice, dyslipidemic mice, and diabetic mice. Results . Diabetes significantly increased OPG and the OPG/TRAIL ratio expression in the aorta, while dyslipidemia was the major determinant of the changes observed in the heart, where it significantly increased OPG and reduced TRAIL expression, thus increasing cardiac OPG/TRAIL ratio. Conclusions . This work shows that both dyslipidemia and diabetes affect OPG/TRAIL ratio in the cardiovascular system. This could contribute to the changes in circulating OPG/TRAIL which are observed in patients with diabetes and CVD. Most importantly, these changes could mediate/contribute to atherosclerosis development and cardiac remodeling.

Favorable Alleles for Stem Water-Soluble Carbohydrates Identified by Association Analysis Contribute to Grain Weight under Drought Stress Conditions in Wheat

PubMed Central

Li, Runzhi; Chang, Xiaoping; Jing, Ruilian

2015-01-01

Drought is a major environmental constraint to crop distribution and productivity. Stem water-soluble carbohydrates (WSC) buffer wheat grain yield against conditions unfavorable for photosynthesis during the grain filling stage. In this study, 262 winter wheat accessions and 209 genome-wide SSR markers were collected and used to undertake association analysis based on a mixed linear model (MLM). The WSC in different internodes at three growth stages and 1000-grain weight (TGW) were investigated under four environmental regimes (well-watered, drought stress during the whole growth period, and two levels of terminal drought stress imposed by chemical desiccation under the well-watered and drought stress during the whole growth period conditions). Under diverse drought stress conditions, WSC in lower internodes showed significant positive correlations with TGW, especially at the flowering stage under well-watered conditions and at grain filling under drought stress. Sixteen novel WSC-favorable alleles were identified, and five of them contributed to significantly higher TGW. In addition, pyramiding WSC favorable alleles was not only effective for obtaining accessions with higher WSC, but also for enhancing TGW under different water regimes. During the past fifty years of wheat breeding, WSC was selected incidentally. The average number of favorable WSC alleles increased from 1.13 in the pre-1960 period to 4.41 in the post-2000 period. The results indicate a high potential for using marker-assisted selection to pyramid WSC favorable alleles in improving WSC and TGW in wheat. PMID:25768726

A randomized trial of a community-based approach to dyslipidemia management: Pharmacist prescribing to achieve cholesterol targets (RxACT Study).

PubMed

Tsuyuki, Ross T; Rosenthal, Meagen; Pearson, Glen J

2016-09-01

Dyslipidemia is an important risk factor for cardiovascular disease but is suboptimally managed. Pharmacists are accessible primary care professionals and with expanded scopes of practice (including prescribing), could identify and manage patients with dyslipidemia. We sought to evaluate the effect of pharmacist prescribing of dyslipidemia medications on the proportion of participants achieving target LDL-cholesterol (LDL-c) levels. We conducted a randomized controlled trial in 14 community pharmacies in Alberta, Canada. We enrolled adults with uncontrolled dyslipidemia as defined by the 2009 Canadian Dyslipidemia Guidelines. Intervention was pharmacist-directed dyslipidemia care, including assessment of cardiovascular risk, review of LDL-c, prescribing of medications, health behaviour interventions and follow-up every 6 weeks for 6 months. Usual care patients received their lipid results and a pamphlet on cardiovascular disease and usual care from their physician and pharmacist. Primary outcome was the proportion of participants achieving their target LDL-c (<2 mmol/L or ≥50% reduction) at 6 months between groups. We enrolled 99 patients with a mean (SD) age of 63 (13) years, 49% male and baseline LDL-c of 3.37 mmol/L (0.98). Proportion of patients achieving LDL-c target was 43% intervention versus 18% control ( p = 0.007). Adjusted odds of achieving target LDL-c were 3.3 times higher for the intervention group ( p = 0.031), who also achieved greater reduction in LDL-c (1.12 mmol/L, SE = 0.112) versus control (0.42 mmol/L, SE = 0.109), for an adjusted mean difference of 0.546 mmol/L (SE = 0.157), p < 0.001. Pharmacist prescribing resulted in >3-fold more patients achieving target LDL-c levels. This could have major public health implications.

Dyslipidemia awareness, treatment, control and influence factors among adults in the Jilin province in China: a cross-sectional study.

PubMed

He, Huan; Yu, Ya-qin; Li, Yong; Kou, Chang-gui; Li, Bo; Tao, Yu-chun; Zhen, Qing; Wang, Chang; Kanu, Joseph Sam; Huang, Xu-feng; Han, Mei; Liu, Ya-wen

2014-08-03

In China, even though the prevalence of dyslipidemia among adults increased yearly and dyslipidemia being an important risk factor for cardiovascular diseases among the Chinese population, however, the awareness, treatment and control of dyslipidemia are at low levels, and only limited studies on the influence factors associated with the awareness, treatment and control dyslipidemia in China have been carried out. The analysis was based on a representative sample of 7138 adult subjects aged 18~79 years recruited from a cross-sectional study of chronic disease and risk factors among adults in the Jilin province in 2012. Chi-square test was used to compare the rates of dyslipidemia awareness, treatment and control between different characteristics of participants. Multiple logistic regression analyses were performed separately for each group to explore the associations between participants' characteristics and dyslipidemia awareness, treatment and control. Among participants with dyslipidemia, 11.6% were aware of the diagnosis, 8.4% were receiving treatment, and 34.8% had dyslipidemia controlled. Increase in age and BMI ≥ 24 kg/m2 were by far the strongest risk factors associated with better awareness and treatment of dyslipidemia. Retirees were more likely to be aware of their dyslipidemia condition (OR=1.255; 95% CI: 1.046, 1.506) and to be receiving treatment (OR=1.367; 95% CI: 1.114, 1.676) than manual workers. A family history of dyslipidemia increased the likelihood of awareness (OR=3.620; 95% CI: 2.816, 4.653) and treatment (OR=3.298; 95% CI: 2.488, 4.371) of dyslipidemia. Alcohol drinking and physical activity were associated with a lower level of awareness and treatment.Cigarette smokers (OR=0.501; 95% CI: 0.349, 0.719) and those with BMI ≥ 24 kg/m2 (OR=0.480; 95% CI: 0.326, 0.706) who received treatment were also associated with poor dyslipidemia control. Our study highlights low levels of awareness, poor treatment and control of dyslipidemia among

Prevalence and Management of Dyslipidemia in Korea: Korea National Health and Nutrition Examination Survey during 1998 to 2010.

PubMed

Roh, Eun; Ko, Seung-Hyun; Kwon, Hyuk-Sang; Kim, Nan Hee; Kim, Jae Hyeon; Kim, Chul Sik; Song, Kee-Ho; Won, Jong Chul; Kim, Dae Jung; Choi, Sung Hee; Lim, Soo; Cha, Bong-Yun

2013-12-01

Dyslipidemia is a major risk factor of cardiovascular disease. The aim of this study was to investigate the changing trends in the prevalence and management status of dyslipidemia among Korean adults. The prevalence of dyslipidemia and the rates of awareness, treatment, and control of dyslipidemia were investigated in adults aged ≥20 years from the Korea National Health and Nutrition Surveys (KNHANES) 1998 to 2010. The updated National Cholesterol Education Program criteria was used, which define dyslipidemia as having one or more of the following lipid abnormalities: hypercholesterolemia (total cholesterol ≥240 mg/dL or diagnosis of dyslipidemia or use of lipid-lowering drugs), hypertriglyceridemia (≥150 mg/dL), hyper-low density lipoprotein (LDL) cholesterolemia (≥160 mg/dL or diagnosis of dyslipidemia or use of lipid-lowering drugs), and hypo-high density lipoprotein (HDL)-cholesterolemia (<40 mg/dL in men and <50 mg/dL in women). The number of participants was 6,921, 4,894, 5,312, 2,733, 6,295, 6,900, and 5,738 in KNHANES 1998, 2001, 2005, 2007, 2008, 2009, and 2010, respectively. Age-standardized prevalence rates of dyslipidemia were 54.0%, 65.8%, 66.5%, 60.6%, 58.7%, 58.9%, and 59.0% in 1998, 2001, 2005, 2007, 2008, 2009, and 2010, respectively. Hypertriglyceridemia and hypo-HDL-cholesterolemia were the two most frequent lipid abnormalities. The overall prevalence of hypercholesterolemia and hyper-LDL-cholesterolemia increased by 1.36- and 1.35-fold in 2010 compared with 2007, respectively. Awareness, treatment, and control rates of dyslipidemia improved over the period of surveys in both sexes. In 2010, about 30% of dyslipidemic patients who received lipid-lowering treatment reached target levels. Although the management status of dyslipidemia has improved during recent years, effective strategy is required for achieving better prevention, treatment, and control of dyslipidemia.

Effects of High Intensity Statin Therapy in the Treatment of Diabetic Dyslipidemia in Patients with Coronary Artery Disease.

PubMed

Vavlukis, Marija; Kedev, Sasko

2018-01-01

Diabetic dyslipidemia has specifics that differ from dyslipidemia in patients without diabetes, which contributes to accelerated atherosclerosis equally as dysglycemia. The aim of this study was to deduce the interdependence of diabetic dyslipidemia and cardiovascular diseases (CVD), therapeutic strategies and the risk of diabetes development with statin therapy. We conducted a literature review of English articles through PubMed, PubMed Central and Cochrane, on the role of diabetic dyslipidemia in atherosclerosis, the antilipemic treatment with statins, and the role of statin therapy in newly developed diabetes, by using key words: atherosclerosis, diabetes mellitus, diabetic dyslipidemia, CVD, statins, nicotinic acid, fibrates, PCSK9 inhibitors. hyperglycemia and dyslipidemia cannot be treated separately in patients with diabetes. It seems that dyslipidemia plays one of the key roles in the development of atherosclerosis. High levels of TG, decreased levels of HDL-C and increased levels of small dense LDL- C particles in the systemic circulation are the most specific attributes of diabetic dyslipidemia, all of which originate from an inflated flux of free fatty acids occurring due to the preceding resistance to insulin, and exacerbated by elevated levels of inflammatory adipokines. Statins are a fundamental treatment for diabetic dyslipidemia, both for dyslipidemia and for CVD prevention. The use of statin treatment with high intensity is endorsed for all diabetes-and-CVD patients, while a moderate - intensity treatment can be applied to patients with diabetes, having additional risk factors for CVD. Statins alone are thought to possess a small, although of statistical significance, risk of incident diabetes, outweighed by their benefits. As important as hyperglycemia and glycoregulation are in CVD development in patients with diabetes, diabetic dyslipidemia plays an even more important role. Statins remain the cornerstone of antilipemic treatment in diabetic

[Association between venous thrombosis and dyslipidemia].

PubMed

García Raso, Aránzazu; Ene, Gabriela; Miranda, Carolina; Vidal, Rosa; Mata, Raquel; Llamas Sillero, M Pilar

2014-07-07

Venous and arterial thrombosis, despite being historically considered as distinct conditions, share certain risk factors. Dyslipidemia is a clinical condition with a relatively high prevalence in the population and has been associated with an increased thrombotic risk. Lipids and lipoproteins modulate the expression and/or function of thrombotic, fibrinolytic and rheological factors. We have developed a descriptive, retrospective, comparative, cross-sectional study including a group of 313 patients with venous thromboembolism (VTE). We collected basic demographic data, cardiovascular risk factors and thrombotic complications. All patients were subjected to a lipid profile study with determination of total cholesterol, high density lipoprotein cholesterol (cHDL), low density lipoprotein cholesterol (cLDL) and triglycerides. The multivariable analysis showed that dyslipidemia was a risk factor for VTE (odds ratio [OR] 3.87, 95% confidence interval [95% CI] 2.72-5.56; P<.0001). Of a total of 313 patients included in the study, 31% (n=97) had a recurrent thrombotic event and 23% (n=72) developed post-thrombotic syndrome. cHDL levels below 35 mg/dl and cLDL levels higher than 180 mg/dl represented risk factors for the development of recurrent thrombosis, OR 3.12 (95% CI 1.35-7.74; P=.008) and OR 2.35 (95% CI 1.24-4.45; P=.008), respectively, and post-thrombotic syndrome, OR 3.44 (95% CI 1.43-8.83; P=.005) and OR 2.35 (95% CI 1.24-4.45; P=.008). Our study confirmed the association between dyslipidemia and VTE and showed a risk of thrombosis nearly 4 times higher in individuals with this disease. In addition, alterations in the lipid profile were also related to a higher prevalence of thrombotic complications, recurrence and post-thrombotic syndrome. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Individual and Joint Associations of Methylenetetrahydrofolate Reductase C677T Genotype and Plasma Homocysteine With Dyslipidemia in a Chinese Population With Hypertension.

PubMed

Liu, Yanhong; Li, Kang; Venners, Scott A; Hsu, Yi-Hsiang; Jiang, Shanqun; Weinstock, Justin; Wang, Binyan; Tang, Genfu; Xu, Xiping

2017-04-01

We aimed to examine the cross-sectional associations of plasma total homocysteine (tHcy) concentrations and methylenetetrahydrofolate reductase ( MTHFR) C677T genotype with dyslipidemia. A total of 231 patients with mild-to-moderate essential hypertension were enrolled from the Huoqiu and Yuexi communities in Anhui Province, China. Plasma tHcy levels were measured by high-performance liquid chromatography. Genotyping was performed by TaqMan allelic discrimination technique. Compared with MTHFR 677 CC + CT genotype carriers, TT genotype carriers had higher odds of hypercholesterolemia (adjusted odds ratio [OR] [95% confidence interval (CI)]: 2.7 [1.4-5.2]; P = .004) and higher odds of abnormal low-density lipoprotein cholesterol (adjusted OR [95% CI]: 2.3 [1.1-4.8]; P = .030). The individuals with the TT genotype had higher concentrations of log(tHcy) than those with the 677 CC + CT genotype (adjusted β [standard error]: .2 [0.03]; P < .001). Patients with tHcy ≥ 10 μmol/L had significantly higher odds of hypercholesterolemia (adjusted OR [95% CI]: 2.4 [1.2-4.7]; P = .010). Furthermore, patients with both the TT genotype and the tHcy ≥ 10 μmol/L had the highest odds of hypercholesterolemia (adjusted OR [95% CI]: 4.1 [1.8-9.4]; P = .001) and low-density lipoprotein cholesterol (adjusted OR [95% CI]: 2.4 [1.0-6.0]; P = .064). This study suggests that both tHcy and the MTHFR C677T gene polymorphism may be important determinants of the incidence of dyslipidemia in Chinese patients with essential hypertension. Further studies are needed to confirm the role of tHcy and the MTHFR C677T mutation in the development of dyslipidemia in a larger sample.

Human minisatellite alleles detectable only after PCR amplification.

PubMed

Armour, J A; Crosier, M; Jeffreys, A J

1992-01-01

We present evidence that a proportion of alleles at two human minisatellite loci is undetected by standard Southern blot hybridization. In each case the missing allele(s) can be identified after PCR amplification and correspond to tandem arrays too short to detect by hybridization. At one locus, there is only one undetected allele (population frequency 0.3), which contains just three repeat units. At the second locus, there are at least five undetected alleles (total population frequency 0.9) containing 60-120 repeats; they are not detected because these tandem repeats give very poor signals when used as a probe in standard Southern blot hybridization, and also cross-hybridize with other sequences in the genome. Under these circumstances only signals from the longest tandemly repeated alleles are detectable above the nonspecific background. The structures of these loci have been compared in human and primate DNA, and at one locus the short human allele containing three repeat units is shown to be an intermediate state in the expansion of a monomeric precursor allele in primates to high copy number in the longer human arrays. We discuss the implications of such loci for studies of human populations, minisatellite isolation by cloning, and the evolution of highly variable tandem arrays.

[A new human leukocyte antigen class I allele, HLA- B*52:11].

PubMed

Li, Xiao-feng; Zhang, Xu; Zhang, Kun-lian; Chen, Yang; Liu, Xian-zhi; Li, Jian-ping

2011-12-01

To identify and confirm a novel HLA allele. A new human leukocyte antigen class I allele was found during routine HLA genotyping by polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) and sequencing-based typing (SBT). The novel HLA-B*52 allele was identical to B*52:01:01 with an exception of one base substitution at position 583 of exon 3 where a C was changed to T resulting in codon 195 changed from CAC(H) to TAC(Y). A new HLA class I allele, B*52:11, is identified, and is named officially by the WHO Nomenclature Committee.

Comprehensive Analysis of Established Dyslipidemia-Associated Loci in the Diabetes Prevention Program

PubMed Central

Varga, Tibor V.; Winters, Alexandra H.; Jablonski, Kathleen A.; Horton, Edward S.; Khare-Ranade, Prajakta; Knowler, William C.; Marcovina, Santica M.; Renström, Frida; Watson, Karol E.; Goldberg, Ronald; Florez, José C.

2016-01-01

Background We assessed whether 234 established dyslipidemia-associated loci modify the effects of metformin treatment and lifestyle intervention (vs. placebo control) on lipid and lipid sub-fraction levels in the Diabetes Prevention Program (DPP) randomized controlled trial. Methods and Results We tested gene-treatment interactions in relation to baseline adjusted follow-up blood lipid concentrations (high and low density lipoprotein cholesterol [HDL-C, LDL-C], total cholesterol, triglycerides) and lipoprotein sub-fraction particle concentrations and size in 2,993 participants with pre-diabetes. Of the previously reported SNP associations, 32.5% replicated at P<0.05 with baseline lipid traits. Trait-specific genetic risk scores (GRS) were robustly associated (3×10−4>P>1.1×10−16) with their respective baseline traits for all but two traits. Lifestyle modified the effect of the GRS for large HDL particle numbers, such that each risk allele of the GRSHDL-large was associated with lower concentrations of large HDL particles at follow-up in the lifestyle arm (β=−0.11 μmol/l per GRS risk allele; 95%CI −0.188, −0.033; P=5×10−3; Pinteraction=1×10−3 for lifestyle vs. placebo), but not in the metformin or placebo arms (P>0.05). In the lifestyle arm, participants with high genetic risk had more favorable or similar trait levels at 1-yr compared to participants at lower genetic risk at baseline for 17 of the 20 traits. Conclusions Improvements in large HDL particle concentrations conferred by lifestyle may be diminished by genetic factors. Lifestyle intervention, however, was successful in offsetting unfavorable genetic loading for most lipid traits. PMID:27784733

Dyslipidemia awareness, treatment, control and influence factors among adults in the Jilin province in China: a cross-sectional study

PubMed Central

2014-01-01

Background In China, even though the prevalence of dyslipidemia among adults increased yearly and dyslipidemia being an important risk factor for cardiovascular diseases among the Chinese population, however, the awareness, treatment and control of dyslipidemia are at low levels, and only limited studies on the influence factors associated with the awareness, treatment and control dyslipidemia in China have been carried out. Methods The analysis was based on a representative sample of 7138 adult subjects aged 18 ~ 79 years recruited from a cross-sectional study of chronic disease and risk factors among adults in the Jilin province in 2012. Chi-square test was used to compare the rates of dyslipidemia awareness, treatment and control between different characteristics of participants. Multiple logistic regression analyses were performed separately for each group to explore the associations between participants’ characteristics and dyslipidemia awareness, treatment and control. Results Among participants with dyslipidemia, 11.6% were aware of the diagnosis, 8.4% were receiving treatment, and 34.8% had dyslipidemia controlled. Increase in age and BMI ≥ 24 kg/m2 were by far the strongest risk factors associated with better awareness and treatment of dyslipidemia. Retirees were more likely to be aware of their dyslipidemia condition (OR = 1.255; 95% CI: 1.046, 1.506) and to be receiving treatment (OR = 1.367; 95% CI: 1.114, 1.676) than manual workers. A family history of dyslipidemia increased the likelihood of awareness (OR = 3.620; 95% CI: 2.816, 4.653) and treatment (OR = 3.298; 95% CI: 2.488, 4.371) of dyslipidemia. Alcohol drinking and physical activity were associated with a lower level of awareness and treatment. Cigarette smokers (OR = 0.501; 95% CI: 0.349, 0.719) and those with BMI ≥ 24 kg/m2 (OR = 0.480; 95% CI: 0.326, 0.706) who received treatment were also associated with poor dyslipidemia control. Conclusion Our

Dyslipidemia and its association with meibomian gland dysfunction.

PubMed

Braich, Puneet S; Howard, Mary K; Singh, Jorawer S

2016-08-01

Abnormal serum lipid levels significantly increase the risk for cardiovascular disease. Furthermore, abnormal compositions of cholesterol in glandular secretions have been hypothesized as an etiology for meibomian gland dysfunction, yet this relationship has not been well studied in clinical settings. The primary purpose of this study was to determine if there is an association between dyslipidemia and meibomian gland dysfunction (MGD). The secondary purpose was to identify the factors, if any, that play a role in this association. A case-control study was performed between October 2013 and February 2015 which recruited 109 patients with MGD and 115 control patients without MGD. All participants were of Indian descent and had no history of dyslipidemia. Basic demographic information was collected as well as fasting levels of serum glucose, creatinine, triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). To calculate differences between groups, Z test or Student t test were used. A stepwise logistic regression model was used to calculate the estimates of odds ratios (ORs), where MGD was the dependent variable, making the independent variables consist of sex, age, body mass index (BMI), triglycerides ≥150 mg/dL, total cholesterol ≥200 mg/dL, LDL ≥130 mg/dL, or HDL ≤40 mg/dL, serum glucose, and serum creatinine. Dyslipidemia, defined by either a fasting total cholesterol level of ≥ 200 mg/dL, triglycerides ≥150 mg/dL, LDL ≥130 mg/dL, or HDL ≤40 mg/dL, was detected in 70 cases (64 %) and 21 controls (18 %), P < 0.001. Mean levels of triglycerides, total cholesterol, LDL, and HDL were 98.5 ± 42.1, 203.1 ± 13.2, 126.1 ± 10.2, and 53.3 ± 4.2 mg/dL, respectively, in cases and 82.3 ± 36.5, 156.6 ± 14.5, 92.2 ± 12.4, 45.8 ± 2.6 mg/dL, respectively, in controls. All differences were statistically significant (P < 0.05). MGD was significantly associated with age >65�

New insights into the pathophysiology of dyslipidemia in type 2 diabetes.

PubMed

Taskinen, Marja-Riitta; Borén, Jan

2015-04-01

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality for patients with type 2 diabetes, despite recent significant advances in management strategies to lessen CVD risk factors. A major cause is the atherogenic dyslipidemia, which consists of elevated plasma concentrations of both fasting and postprandial triglyceride-rich lipoproteins (TRLs), small dense low-density lipoprotein (LDL) and low high-density lipoprotein (HDL) cholesterol. The different components of diabetic dyslipidemia are not isolated abnormalities but closely linked to each other metabolically. The underlying disturbances are hepatic overproduction and delayed clearance of TRLs. Recent results have unequivocally shown that triglyceride-rich lipoproteins and their remnants are atherogenic. To develop novel strategies for the prevention and treatment of dyslipidaemia, it is essential to understand the pathophysiology of dyslipoproteinaemia in humans. Here, we review recent advances in our understanding of the pathophysiology of diabetic dyslipidemia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

ALEA: a toolbox for allele-specific epigenomics analysis.

PubMed

Younesy, Hamid; Möller, Torsten; Heravi-Moussavi, Alireza; Cheng, Jeffrey B; Costello, Joseph F; Lorincz, Matthew C; Karimi, Mohammad M; Jones, Steven J M

2014-04-15

The assessment of expression and epigenomic status using sequencing based methods provides an unprecedented opportunity to identify and correlate allelic differences with epigenomic status. We present ALEA, a computational toolbox for allele-specific epigenomics analysis, which incorporates allelic variation data within existing resources, allowing for the identification of significant associations between epigenetic modifications and specific allelic variants in human and mouse cells. ALEA provides a customizable pipeline of command line tools for allele-specific analysis of next-generation sequencing data (ChIP-seq, RNA-seq, etc.) that takes the raw sequencing data and produces separate allelic tracks ready to be viewed on genome browsers. The pipeline has been validated using human and hybrid mouse ChIP-seq and RNA-seq data. The package, test data and usage instructions are available online at http://www.bcgsc.ca/platform/bioinfo/software/alea CONTACT: : mkarimi1@interchange.ubc.ca or sjones@bcgsc.ca Supplementary information: Supplementary data are available at Bioinformatics online. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Prevalence of dyslipidemia and associated factors among the hypertensive population from rural Northeast China.

PubMed

Yu, Shasha; Yang, Hongmei; Guo, Xiaofan; Zhang, Xingang; Zheng, Liqiang; Sun, Yingxian

2015-11-21

Our latest study reported the grim status of hypertension in rural China with the prevalence of hypertension reached 51.1%. However, we lack the latest data about the prevalence and epidemiological features of dyslipidemia among hypertensive residents in rural China. A cross-sectional survey was conducted from July 2012 to August 2013 through a cluster multistage sampling to a resident group of 4048 individuals (2152 men, 2896 women) with hypertension, age ≥ 35 years, in the rural Northeast China. Serum lipids level were proposed by National Cholesterol Education Program Adult Treatment Panel III. Of the hypertension residents without antihypertension treatment, 34.5% had borderline high total cholesterol, 19.2% had high total cholesterol, 11.4% had low high-density lipoprotein cholesterol and 37.4% had high non HDL-C. The population with borderline high, high, and very high low-density lipoprotein cholesterol was 20.9, 6.7 and 2.3%, respectively. In addition, 14.3% had borderline high triglycerides, 17.4% had high TG and 2.4% had very high TG. The awareness rate of dyslipidemia among the study population was 5.9%. After adjusting for independent variables, fasting plasma glucose, body mass index, Han nationality, current drinking and smoking, higher annual income and classification of blood pressure were risk factors for dyslipidemia while moderate physical activity was protective factor for dyslipidemia. On the contrary, gender and current drinking decrease the risk of HDL-C. The prevalence of dyslipidemia was dramatically high and dyslipidemia screening was in-need in all diagnosed hypertensive individuals.

[Prevalence and risk factors of dyslipidemia in a rural population of Henan Province, China].

PubMed

Zhou, J M; Luo, X P; Wang, S; Yin, L; Pang, C; Wang, G A; Shen, Y X; Wu, D T; Zhang, L; Ren, Y C; Wang, B Y; Yang, X Y; Zhang, H Y; Han, C Y; Zhao, Y; Li, L L; Wang, C J; Feng, T P; Zhao, J Z; Hu, D S; Zhang, M

2016-09-06

Objective: The purpose of this study was to investigate the prevalence and risk factors of dyslipidemia in a rural population of Henan Province, China. Methods: A total of 20 194 participants aged ≥18 years were selected randomly by cluster sampling from two townships(towns)in Henan Province from July to August 2007 and July to August 2008. Investigations included questionnaires, anthropometric measurements, fasting plasma glucose, and lipid profile examination at baseline. A total of 16 155 participants were followed up from July to August 2013 and July to October 2014. Overall, 13 869 participants were included in the study, after excluding 2 286 participants with incomplete dyslipidemia follow-up data. Distributions of the characteristics of dyslipidemia were determined, and prevalence was standardized by age according to data of the 2010 Sixth National Population Census. Risk factors for dyslipidemia were analyzed using a logistic regression model after adjusting for sex, age, education level, marital status, and income status. Results: The prevalence of dyslipidemia was 53.72%(7 450/13 869)for residents aged ≥22 years living in rural areas of Henan Province(59.32%(3 069/5 174)for men and 50.39%(4 381/8 695)for women). The adjusted prevalence of dyslipidemia was 50.50%(59.27% for men and 45.53% for women). The prevalence of hypercholesterolemia, hypertriglyceridemia, low HDL-C, and high LDL-C was 4.34%(602/13 868), 20.42%(2 826/13 837), 42.75%(5 927/13 865), and 3.14%(420/13 375), respectively, and the adjusted prevalence was 2.44%, 18.84%, 41.42%, and 1.86%, respectively. Logistic regression analyses showed that alcohol consumption( OR =1.27, 95% CI : 1.05-1.53), family history of hyperlipidemia( OR =1.29, 95% CI : 1.17-1.43), overweight( OR =1.40, 95% CI : 1.22-1.61), obesity( OR = 1.65, 95% CI : 1.39- 1.96), abnormal waist circumference( OR =1.22, 95% CI : 1.04- 1.43), and abnormal waist-height ratio( OR =1.21, 95% CI : 1.01-1.45)were significant

Treatment of Dyslipidemias to Prevent Cardiovascular Disease in Patients with Type 2 Diabetes.

PubMed

Khavandi, Maryam; Duarte, Francisco; Ginsberg, Henry N; Reyes-Soffer, Gissette

2017-01-01

Current preventive and treatment guidelines for type 2 diabetes have failed to decrease the incidence of comorbidities, such as dyslipidemia and ultimately heart disease. The goal of this review is to describe the physiological and metabolic lipid alterations that develop in patients with type 2 diabetes mellitus. Questions addressed include the differences in lipid and lipoprotein metabolism that characterize the dyslipidemia of insulin resistance and type 2 diabetes mellitus. We also examine the relevance of the new AHA/ADA treatment guidelines to dyslipidemic individuals. In this review, we provide an update on the pathophysiology of diabetic dyslipidemia, including the role of several apolipoproteins such as apoC-III. We also point to new studies and new agents for the treatment of individuals with type 2 diabetes mellitus who need lipid therapies. Type 2 diabetes mellitus causes cardiovascular disease via several pathways, including dyslipidemia characterized by increased plasma levels of apoB-lipoproteins and triglycerides, and low plasma concentrations of HDL cholesterol. Treatments to normalize the dyslipidemia and reduce the risk for cardiovascular events include the following: lifestyle and medication, particularly statins, and if necessary, ezetimibe, to significantly lower LDL cholesterol. Other treatments, more focused on triglycerides and HDL cholesterol, are less well supported by randomized clinical trials and should be used on an individual basis. Newer agents, particularly the PCSK9 inhibitors, show a great promise for even greater lowering of LDL cholesterol, but we await the results of ongoing clinical trials.

Correlation between homocysteine and dyslipidemia in ischaemic stroke patients with and without hypertension

NASA Astrophysics Data System (ADS)

Aria Arina, Cut; Amir, Darwin; Siregar, Yahwardiah; Sembiring, Rosita J.

2018-03-01

Almost 80% of strokes are ischaemic and stroke is the third most common cause of death in developed countries, . The treatment of stroke still limited, the best approach to reduce mortality and morbidity is primary prevention through modification of acquired risk factors. Hypertension and dyslipidemia are one of the major risk factor for stroke while homocysteine is a less well-documented risk factor. The purpose of this study was to know the correlation between homocysteine and dyslipidemia in ischaemic stroke patients with and without hypertension. This study is a cross sectional study; the sample were taken consecutively. All sample matched with inclusion and exclusion criteria, demography data and blood sample were taken. Demography data was analyzed using descriptive statistic, to analyze the relation, we used Chi-Square test. p value <0,05 was significant. Of the 100 patients, were divided into two groups, with hypertension, and without hypertension, hyperhomocysteinemia was found in 62 patients (59 patients had mild hyperhomocysteinemia, three patients had moderate hyperhomocysteinemia) and dyslipidemia was found in 60 patients. There is a significant relation between homocysteine and dyslipidemia in ischaemic stroke patients with hypertension, p value = 0,009. A significant correlation between homocysteine and dyslipidemia might be because both of them have an important role in the acceleration of the atherosclerotic formation by activation platelet and thrombus, but we still need further study to get more explanation about the relation.

Pleiotropic Effects of Losartan in Hypertensive Patients with Dyslipidemia.

PubMed

Sivasubramaniam, Sivakumar; Kumarasamy, Banupriya

2017-09-01

In essential hypertension, the comorbidity of dyslipidemia is very common. In addition to hypertension, dyslipidemia is linked to cardiovascular disease, stroke and decline in renal function. Unlike other angiotensin receptor blockers, Losartan has been claimed to have unique pleiotropic property and thereby decreasing the risk of future cardiovascular complications. The present study was done to assess on the pleiotropic effect of losartan in newly diagnosed hypertensive patients with dyslipidemia. Fifty four hypertensive patients with dyslipidemia who fulfilled the eligible criteria and were willing to give informed consent were included in the study after getting Institutional Ethical Committee (IEC) approval. All the study participants were given tab. Losartan 50mg once daily for four weeks. At the end of 1st, 2nd, 3rd and 4th week, blood pressure control and compliance were monitored. At the end of 4th week all the baseline laboratory parameters like renal function test, liver function test, lipid prolife and random blood sugar were performed. The EQ-5D questionnaires were completed at two points during the study: at the patient's initial visit before enrollment in the study and after 4 weeks of Losartan therapy. Appropriate statistical methods were used to analyse the results.The primary endpoint was reduction in blood pressure and improvement in lipid profile and improvement in quality of life score from baseline after 4 weeks of losartan therapy. Four patients were withdrawn due to non-compliance and totally 50 patients completed the study. The mean systolic blood pressure was reduced from 154.54 mm Hg to 138.16 mm Hg with p<0.0001 and the mean diastolic blood pressure was reduced from 91.56 mm Hg to 82.44 mm Hg with p<0.0001. There was a significant reduction in the mean total cholesterol from 189.52 to 180.46 mg/dl, mean LDL from 110.50 to 101.32 mg/dl and mean triglygeride from 135.68 to 127.70 mg/dl with p<0.0001. Improvements in anxiety and depression

[A survey of correlation between serum 25-hydroxyvitamin D levels and dyslipidemia rlsk among middle-aged individuals in Beijing].

PubMed

Zhang, L L; Lu, Y H; Cheng, X L; Liu, M Y; Sun, B R; Li, C L

2016-08-01

To evaluate vitamin D status in middle-aged subjects in Beijing and explore the correlation between serum 25-hydroxyvitamin D[25(OH)D] levels and dyslipidemia. A total of 448 individuals over 40 years old were enrolled in the cross-sectional survey. The general information, blood biochemical and lipid profiles and serum 25(OH)D levels were collected. The subjects were either divided into two groups (the dyslipidemia group and the non-dyslipidemia group) based on the lipid levels, or four groups according to quartiles of 25(OH)D levels. The association between 25(OH)D levels and dyslipidemia risk was analyzed by a logistic regression analysis. A total of 234 cases were in dyslipidemia group, which accounted for 52.23% of the subjects. The serum 25(OH)D levels were significantly lower in the dyslipidemia group than in the non-dyslipidemia group both in men and in women (all P<0.05). The median serum 25(OH)D level in the total subjects was 15.7 (12.2, 20.1)μg/L with 91.1% subjects of serum 25(OH)D level<30 μg/L. The proportion of subjects with dyslipidemia (high TC, high TG, high LDL-C, or low HDL-C) increased with the decrease of 25(OH)D level quartiles (P<0.05). After adjustment of confounding factors, the logistic regression analysis showed that subjects in the lowest 25(OH) D quartile group had 143% higher risks for dyslipidemia than those in the highest quartile group. These findings indicate that 25(OH)D insufficiency is highly prevalent among middle-aged individuals and it may be associated with the risk of dyslipidemia.

The prevalence, awareness, treatment, and control of dyslipidemia in northeast China: a population-based cross-sectional survey.

PubMed

Zhang, Fu-Liang; Xing, Ying-Qi; Wu, Yan-Hua; Liu, Hao-Yuan; Luo, Yun; Sun, Ming-Shuo; Guo, Zhen-Ni; Yang, Yi

2017-03-23

Dyslipidemia is an important independent modifiable risk factor for cardiovascular disease. The aim of this study was to explore the current prevalence, awareness, treatment and control of dyslipidemia and its associated influence factors in northeast China. In this population-based cross-sectional study, we adopted a multi-stage, stratified sampling method to obtain a representative sample of 4052 permanent residents aged 40 years and over from different urban and rural regions in Dehui City of Jilin Province. All subjects completed a questionnaire and were examined for risk factors. Continuous data were presented as means ± standard deviations (SD) and compared using the Student's t-test. Categorical variables were presented as proportions and compared using the Rao-Scott-χ 2 test in different subgroups. The associated influence factors for the prevalence, awareness, treatment and control of dyslipidemia were evaluated through multivariate logistic regression. The prevalence of dyslipidemia was 62.1% overall, with 33.5, 43.9, 0.6, and 8.8% for high total cholesterol, triglyceride, low-density lipoprotein cholesterol, and low high-density lipoprotein cholesterol, respectively. Among those with dyslipidemia, the proportion of subjects who were aware, treated, and controlled was 14.4, 33.9, and 19.9%, respectively. Overweight or obesity (OR = 2.156; 95% CI: 1.863, 2.533), hypertension (OR = 1.643; 95% CI: 1.425, 1.893), or diabetes mellitus (OR = 2.173; 95% CI: 1.661, 2.844) increased the prevalence of dyslipidemia, also these participants were more likely to be aware of their condition, however, this did not increase the likelihood of treatment and control. Living in urban areas and higher education level also increased the awareness of dyslipidemia. Personal history of coronary heart disease was the strongest influence factors associated with better awareness, treatment and control of dyslipidemia. Overweight or obesity (OR = 0.404; 95% CI

Increased Visceral Adipose Tissue Is an Independent Predictor for Future Development of Atherogenic Dyslipidemia.

PubMed

Hwang, You-Cheol; Fujimoto, Wilfred Y; Hayashi, Tomoshige; Kahn, Steven E; Leonetti, Donna L; Boyko, Edward J

2016-02-01

Atherogenic dyslipidemia is frequently observed in persons with a greater amount of visceral adipose tissue (VAT). However, it is still uncertain whether VAT is independently associated with the future development of atherogenic dyslipidemia. The aim of this study was to determine whether baseline and changes in VAT and subcutaneous adipose tissue (SAT) are associated with future development of atherogenic dyslipidemia independent of baseline lipid levels and standard anthropometric indices. Community-based prospective cohort study with 5 years of follow-up. A total of 452 Japanese Americans (240 men, 212 women), aged 34-75 years were assessed at baseline and after 5 years of follow-up. Abdominal fat areas were measured by computed tomography. Atherogenic dyslipidemia was defined as one or more abnormalities in high-density lipoprotein (HDL) cholesterol, triglycerides, or non-HDL cholesterol levels. Baseline VAT and change in VAT over 5 years were independently associated with log-transformed HDL cholesterol, log-transformed triglyceride, and non-HDL cholesterol after 5 years (standardized β = -0.126, 0.277, and 0.066 for baseline VAT, respectively, and -0.095, 0.223, and 0.090 for change in VAT, respectively). However, baseline and change in SAT were not associated with any future atherogenic lipid level. In multivariate logistic regression analysis, incremental change in VAT (odds ratio [95% confidence interval], 1.73 [1.20-2.48]; P = .003), triglycerides (4.01 [1.72-9.33]; P = .001), HDL cholesterol (0.32 [0.18-0.58]; P < .001), and non-HDL cholesterol (7.58 [4.43-12.95]; P < .001) were significantly associated with the future development of atherogenic dyslipidemia independent of age, sex, diastolic blood pressure, homeostasis model assessment insulin resistance, body mass index (BMI), change in BMI, SAT, and baseline atherogenic lipid levels. Baseline and change in VAT were independent predictors for future development of atherogenic dyslipidemia. However

Thyroid hormone analogs for the treatment of dyslipidemia: past, present, and future.

PubMed

Delitala, Alessandro P; Delitala, Giuseppe; Sioni, Paolo; Fanciulli, Giuseppe

2017-11-01

Treatment of dyslipidemia is a major burden for public health. Thyroid hormone regulates lipid metabolism by binding the thyroid hormone receptor (TR), but the use of thyroid hormone to treat dyslipidemia is not indicated due to its deleterious effects on heart, bone, and muscle. Thyroid hormone analogs have been conceived to selectively activate TR in the liver, thus reducing potential side-effects. The authors searched the PubMed database to review TR and the action of thyromimetics in vitro and in animal models. Then, all double-blind, placebo controlled trials that analyzed the use of thyroid hormone analog for the treatment of dyslipidemia in humans were included. Finally, the ongoing research on the use of TR agonists was searched, searching the US National Institutes of Health Registry and the WHO International Clinical Trial Registry Platform (ICTRP). Thyromimetics were tested in humans for the treatment of dyslipidemia, as a single therapeutic agent or as an add-on therapy to the traditional lipid-lowering drugs. In most trials, thyromimetics lowered total cholesterol, low-density lipoprotein cholesterol, and triglycerides, but their use has been associated with adverse side-effects, both in pre-clinical studies and in humans. The use of thyromimetics for the treatment of dyslipidemia is not presently recommended. Future possible clinical applications might include their use to promote weight reduction. Thyromimetics might also represent an interesting alternative, both for the treatment of non-alcoholic steatohepatitis, and type 2 diabetes due to their positive effects on insulin sensitivity. Finally, additional experimental and clinical studies are needed for a better comprehension of the effect(s) of a long-term therapy.

Association of Dyslipidemia and Sex With Coronary Artery Calcium Assessed by Coronary Computed Tomography Angiography.

PubMed

Asami, Masahiko; Yamaji, Kyohei; Aoki, Jiro; Tanimoto, Shuzou; Watanabe, Mika; Horiuchi, Yu; Furui, Koichi; Kato, Nahoko; Hara, Kazuhiro; Tanabe, Kengo

2017-10-21

Previous studies reporting that statin increases coronary artery calcium (CAC) were conducted exclusively on patients with statin as a prevention, regardless of the presence or absence of dyslipidemia. The impact of sex on CAC has not been fully evaluated. We aimed to determine the association of dyslipidemia and sex with CAC using 320-row multi-detector computed tomography (MDCT).Of the 356 consecutive patients who underwent coronary MDCT, 251 patients were enrolled, after excluding those with prior stenting and/or coronary bypass grafting or images showing motion artifacts. The primary outcome measures were the percent calcium volume (PCV) and percent atheroma volume (PAV) per coronary vessel.Multivariable analyses indicated that PCV was significantly higher in dyslipidemia patients without statins than in the subjects without dyslipidemia [partial regression coefficient (PRC): 2.59, 95% confidence interval (CI): 0.83 to 4.34, P = 0.004]. In contrast, PCV was similar in dyslipidemia patients taking statins and those without dyslipidemia (PRC: -1.09, 95% CI: -2.82 to 0.65, P = 0.22). There was no significant difference in PCV between men and women, although women exhibited a significantly lower PAV (PRC: -2.87, 95% CI: -4.54 to -1.20, P = 0.001).In low-risk patients, these results could be translated into hypotheses, which should be tested in future prospective studies. Furthermore, there was no significant difference in CAC between men and women, but women had lower PAV than men.

Evaluation and Management of Dyslipidemia in Patients with HIV Infection

PubMed Central

Green, Michael L

2002-01-01

OBJECTIVE Persons with HIV infection develop metabolic abnormalities related to their antiretroviral therapy and HIV infection itself. The objective of this study was to summarize the emerging evidence for the incidence, etiology, health risks, and treatment of dyslipidemias in HIV disease. DESIGN Systematic review of original research with quantitative synthesis. MAIN RESULTS Dyslipidemia is common in persons with HIV infection on highly active antiretroviral therapy (HAART), but methodologic differences between studies preclude precise estimates of prevalence and incidence. The typical pattern includes elevated total cholesterol, low-density lipoprotein cholesterol, and triglycerides, which may be markedly elevated. The dyslipidemia may be associated with lipodystrophy, insulin resistance, and, rarely, frank diabetes mellitus. Exposure to protease inhibitors (PIs) is associated with this entire range of metabolic abnormalities. PI-naïve patients on nucleoside reverse transcriptase inhibitors (NRTIs) may develop lipodystrophy, insulin resistance, hypercholesterolemia, and possibly modest elevations in triglycerides but not severe hypertriglyceridemia, which appears to be linked to PIs alone. Most studies have not found an association between CD4 lymphocyte count or HIV viral load and lipid abnormalities. The pathogenesis is incompletely understood and appears to be multifactorial. There are insufficient data to definitively support an increased coronary heart disease risk in patients with HIV-related dyslipidemia. However, some of the same metabolic abnormalities remain firmly established risk factors in other populations. Patients on HAART with severe hypertriglyceridemia may develop pancreatitis or other manifestations of the chylomicronemia syndrome. Some of the metabolic derangements (particularly hypertriglyceridemia) may improve upon replacing a PI with a non-nucleoside reverse transcriptase inhibitor. The limited experience suggests that fibrates

Delimiting Allelic Imbalance of TYMS by Allele-Specific Analysis.

PubMed

Balboa-Beltrán, Emilia; Cruz, Raquel; Carracedo, Angel; Barros, Francisco

2015-07-01

Allelic imbalance of thymidylate synthase (TYMS) is attributed to polymorphisms in the 5'- and 3'-untranslated region (UTR). These polymorphisms have been related to the risk of suffering different cancers, for example leukemia, breast or gastric cancer, and response to different drugs, among which are methotrexate glutamates, stavudine, and specifically 5-fluorouracil (5-FU), as TYMS is its direct target. A vast literature has been published in relation to 5-FU, even suggesting the sole use of these polymorphisms to effectively manage 5-FU dosage. Estimates of the extent to which these polymorphisms influence in TYMS expression have in the past been based on functional analysis by luciferase assays and quantification of TYMS mRNA, but both these studies, as the association studies with cancer risk or with toxicity or response to 5-FU, are very contradictory. Regarding functional assays, the artificial genetic environment created in luciferase assay and the problems derived from quantitative polymerase chain reactions (qPCRs), for example the use of a reference gene, may have distorted the results. To avoid these sources of interference, we have analyzed the allelic imbalance of TYMS by allelic-specific analysis in peripheral blood mononuclear cells (PBMCs) from patients.Allelic imbalance in PBMCs, taken from 40 patients with suspected myeloproliferative haematological diseases, was determined by fluorescent fragment analysis (for the 3'-UTR polymorphism), Sanger sequencing and allelic-specific qPCR in multiplex (for the 5'-UTR polymorphisms).For neither the 3'- nor the 5'-UTR polymorphisms did the observed allelic imbalance exceed 1.5 fold. None of the TYMS polymorphisms is statistically associated with allelic imbalance.The results acquired allow us to deny the previously established assertion of an influence of 2 to 4 fold of the rs45445694 and rs2853542 polymorphisms in the expression of TYMS and narrow its allelic imbalance to 1.5 fold, in our population

Update on the clinical utility of fenofibrate in mixed dyslipidemias: mechanisms of action and rational prescribing

PubMed Central

Farnier, Michel

2008-01-01

Mixed dyslipidemia is a common lipid disorder characterized by the presence of an atherogenic lipoprotein phenotype due to abnormalities in various atherogenic and anti-atherogenic lipoproteins. Despite the link between the decrease of LDL-cholesterol by statin treatment and the prevention of cardiovascular disease, a high residual risk is observed in statin trials. This residual risk is partly explained by lipoprotein abnormalities other than LDL. Fenofibrate exerts a favorable effect on the atherogenic lipid profile of mixed dyslipidemia and can effectively reduce cardiovascular disease in patients with mixed dyslipidemia. Fenofibrate may offer important treatment alternatives as a second-line therapy in several circumstances: in combination with a statin for patients with mixed dyslipidemias not at goals on statin mono-therapy; in monotherapy for patients intolerant or with contraindication to statin therapy; and in combination with other drugs (ezetimibe, colesevelam) for patients with mixed dyslipidemias, known intolerance, or contraindication to statin and not at goals on fenofibrate monotherapy. However, the role of fenofibrate-statin therapy and of other therapies involving fenofibrate in cardiovascular risk reduction strategies remains to be established. PMID:19183747

Association of obesity with hypertension and dyslipidemia in type 2 diabetes mellitus subjects.

PubMed

Anari, Razieh; Amani, Reza; Latifi, Seyed Mahmoud; Veissi, Masoud; Shahbazian, Hajieh

Obesity and diabetes are contributed to cardiovascular disease risk. The current study was performed to evaluate the association of central and general obesity and cardio-metabolic risk factors, including dyslipidemia and hypertension in T2DM patients. This was a cross-sectional study in T2DM adults. Body mass index (BMI) was used to identify general obesity and waist circumference (WC) was measured to define abdominal obesity (based on ATP III). Biochemical analyses, and anthropometric and blood pressure measurements were done for all participants. Participants with central obesity showed significantly higher systolic (132.5mmHg vs. 125.4mmHg, p=0.024) and diastolic blood pressures (84.9mmHg vs. 80mmHg, p=0.007) than participants without obesity. Dyslipidemia was more prevalent in all participants either by BMI (98.3% vs. 97%, 95% CI: 0.18-17.53) or by WC (97.2% vs. 98%, 95% CI: 0.07-7.19). Abdominal adiposity in diabetic subjects showed significant reverse association with high level of physical activity (OR=0.22, 95% CI: 0.06-0.85). Hypertriglyceridemia rate was increased with both central (OR=2.11; p=0.040) and general obesity (OR=2.68; p=0.021). After adjustment for energy intake and age, females had higher risk of general (OR=4.57, 95% CI=1.88-11.11) and central obesity (OR=7.93, 95% CI=3.48-18.08). Females were more susceptible to obesity. Hypertension was associated with both obesity measures. Dyslipidemia, except for hypertriglyceridemia, was correlated to neither abdominal nor general obesity. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

The PNPLA3 rs738409 G-allele associates with reduced fasting serum triglyceride and serum cholesterol in Danes with impaired glucose regulation.

PubMed

Krarup, Nikolaj Thure; Grarup, Niels; Banasik, Karina; Friedrichsen, Martin; Færch, Kristine; Sandholt, Camilla Helene; Jørgensen, Torben; Poulsen, Pernille; Witte, Daniel Rinse; Vaag, Allan; Sørensen, Thorkild; Pedersen, Oluf; Hansen, Torben

2012-01-01

Non-alcoholic fatty liver disease (NAFLD) is a common condition, associated with hepatic insulin resistance and the metabolic syndrome including hyperglycaemia and dyslipidemia. We aimed at studying the potential impact of the NAFLD-associated PNPLA3 rs738409 G-allele on NAFLD-related metabolic traits in hyperglycaemic individuals. The rs738409 variant was genotyped in the population-based Inter99 cohort examined by an oral glucose-tolerance test, and a combined study-sample consisting of 192 twins (96 twin pairs) and a sub-set of the Inter99 population (n = 63) examined by a hyperinsulinemic euglycemic clamp (n(total) = 255). In Inter99, we analyzed associations of rs738409 with components of the WHO-defined metabolic syndrome (n = 5,847) and traits related to metabolic disease (n = 5,663). In the combined study sample we elucidated whether the rs738409 G-allele altered hepatic or peripheral insulin sensitivity. Study populations were divided into individuals with normal glucose-tolerance (NGT) and with impaired glucose regulation (IGR). The case-control study showed no associations with components of the metabolic syndrome or the metabolic syndrome. Among 1,357 IGR individuals, the rs738409 G-allele associated with decreased fasting serum triglyceride levels (per allele effect(β) = -9.9% [-14.4%;-4.0% (95% CI)], p = 5.1×10(-5)) and fasting total cholesterol (β = -0.2 mmol/l [-0.3;-0.01 mmol/l(95% CI)], p = 1.5×10(-4)). Meta-analyses showed no impact on hepatic or peripheral insulin resistance in carriers of the rs738409 G-allele. Our findings suggest that the G-allele of PNPLA3 rs738409 associates with reduced fasting levels of cholesterol and triglyceride in individuals with IGR.

Association between atherogenic dyslipidemia and recurrent stroke risk in patients with different subtypes of ischemic stroke.

PubMed

Zhao, Lu; Wang, Ruihao; Song, Bo; Tan, Song; Gao, Yuan; Fang, Hui; Lu, Jie; Xu, Yuming

2015-07-01

The association between atherogenic dyslipidemia and stroke recurrence remains unclear, and may be influenced by different subtypes of ischemic stroke. We aimed to investigate whether atherogenic dyslipidemia contributed to stroke recurrence in ischemic stroke patients and in those with certain subtypes of ischemic stroke. We conducted a prospective hospital-based study enrolling patients with acute ischemic stroke. Atherogenic dyslipidemia was defined as high-density lipoprotein cholesterol <40 mg/dl and triglycerides ≥200 mg/dl. Ischemic stroke subtypes were classified according to the Trial of Org 10172 in Acute Stroke Treatment criteria. The patients were followed up at 3, 6, 12 and 24 months after stroke onset. The association between atherogenic dyslipidemia and stroke recurrence was analyzed by using multivariable Cox regression model. In the 510 ischemic stroke patients, 64 patients (12·5%) had atherogenic dyslipidemia, and 66 patients (12·9%) experienced stroke recurrence events within 24 months. Kaplan-Meier analysis revealed that stroke recurrence rate was significantly higher in patients with atherogenic dyslipidemia than those without in all the stroke patients (20·3% vs. 11·9%; P = 0·048), and more evident in those of large-artery atherosclerosis subtype (31·0% vs. 14·1%; P = 0·014), but not in the other subtypes. Multivariable Cox regression analysis revealed that atherogenic dyslipidemia was associated with higher stroke recurrence risk among stroke patients of large-artery atherosclerosis subtype (hazard ratio, 2·79; 95% confidence interval, 1·24-6·28), but not significant in all the stroke patients (hazard ratio, 1·69; 95% confidence interval, 0·85-3·37). Atherogenic dyslipidemia is associated with higher risk of stroke recurrence in ischemic stroke patients. Such association might be more pronounced in large-artery atherosclerosis subtype and needs further investigation to establish such relationship. © 2015 World

Impact on Dyslipidemia After Laparoscopic Sleeve Gastrectomy.

PubMed

Vigilante, Agustina; Signorini, Franco; Marani, Marcos; Paganini, Virginia; Viscido, Germán; Navarro, Luciano; Obeide, Lucio; Moser, Federico

2018-06-16

Improvement of dyslipidemia is an important benefit of bariatric surgery. The benefits of laparoscopic sleeve gastrectomy (LSG) among dyslipidemia are still a matter of debate. We conducted a retrospective descriptive study between 2010 and 2013. Obese patients undergoing LSG, with recorded dyslipidemia at admission and a follow-up for at least 1 year, were included for analysis. Demographic characteristics, medication in use, and a complete lipid profile were collected before surgery. After surgery, weight was controlled at 1, 3, 6, and 12 months. Lipid profile was re-evaluated 1 year after surgery. Patients were divided according to weight loss into two groups: (A) adequate weight loss and (B) inadequate weight loss. Lipid profile evolution was then compared between groups. One hundred seven patients met the inclusion criteria. Pre-op mean BMI was 45.13 ± 7.5 kg/m 2 . One year after LSG, mean BMI was 30.6 ± 7.1 kg/m 2 with a change in BMI of 11.5 ± 6.6 kg/m 2 , a %TWL of 26.9 ± 13.5%, and a %EWL of 60.3 ± 36.6%. Hypercholesterolemia and hypertriglyceridemia remission was achieved in 45 and 86% of the patients and improved in another 19 and 4% respectively. Seventy-four percent improved HDL levels. LDL levels improved in 39% and remitted in 37%. Medication was discontinued in 43.7%. HDL increase and LDL, TG, and non-HDL-C decrease were significantly greater in group A. LSG produces an improvement in lipid profile, with a significant increase in HDL and a decrease in LDL, triglycerides, and non-HDL-C.

Vitamin D deficiency and insulin resistance as risk factors for dyslipidemia in obese children.

PubMed

Erol, Meltem; Bostan Gayret, Özlem; Hamilçıkan, Şahin; Can, Emrah; Yiğit, Özgu L

2017-04-01

Dyslipidemia is one of the major complications of obesity; vitamin D deficiency and insulin resistance are attending metabolic complications in dyslipidemic obese children. Objective. To determine if vitamin D deficiency and insulin resistance are risk factors for dyslipidemia in obese children. This study was conducted in the Department of Pediatrics at Bagcilar Training and Research Hospital in Istanbul, Turkey between 2014 and 2015. Obese patients whose age range was 8-14 were included in the study. The serum triglyceride, total cholesterol, low-density lipoprotein cholesterol, highdensity lipoprotein cholesterol, fasting glucose, insulin, alanine aminotransferase, vitamin D levels were measured; a liver ultrasonography was performed. Homeostatic model assessment (HOMA-IR), was used to calculate insulin resistance. 108 obese children were included; 39 (36.11%) had dyslipidemia. The average fasting blood glucose (88.74 ± 7.58 vs. 95.31 ± 6.82; p= 0.0001), insulin level (14.71 ± 12.44 vs. 24.39 ± 15.02; p= 0.0001) and alanine aminotransferase level (23.45 ± 11.18 vs. 30.4 ± 18.95; p= 0.018) were significantly higher in the children with dyslipidemia. In the dyslipidemic obese children, the average hepatosteatosis rate and HOMA-IR level were higher; 28 (71.9%) had hepatosteatosis, 37 (94.87%) had insulin resistance; the vitamin D levels were <20 ng/ml in 69.3%. Vitamin D deficiency was significantly more common (p= 0.033). The multivariate regression analysis confirmed that the increase in the HOMA-IR level (p= 0.015) and the low vitamin D level (p= 0.04) were important risk factors for dyslipidemia. Obese children in our region exhibit low vitamin D and increased HOMA-IR levels, which are efficient risk factors of dyslipidemia.

Awareness, treatment, and control of dyslipidemia in rural South Africa: The HAALSI (Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa) study.

PubMed

Reiger, Sheridan; Jardim, Thiago Veiga; Abrahams-Gessel, Shafika; Crowther, Nigel J; Wade, Alisha; Gomez-Olive, F Xavier; Salomon, Joshua; Tollman, Stephen; Gaziano, Thomas A

2017-01-01

Dyslipidemia is a primary driver for chronic cardiovascular conditions and there is no comprehensive literature about its management in South Africa. The objective of this study was to assess the prevalence, awareness, treatment, and control of dyslipidemia in rural South Africa and how they are impacted by different behaviors and non-modifiable factors. To fulfill this objective we recruited for this cohort study adults aged ≥40 years residing in the Agincourt sub-district of Mpumalanga Province. Data collection included socioeconomic and clinical data, anthropometric measures, blood pressure (BP), HIV-status, point-of-care glucose and lipid levels. Framingham CVD Risk Score was ascribed to patients based upon categories for 10 year cardiovascular risk of low (<3%), moderate (≥3% and <15%), high (≥15% and <30%), and very high (≥30%).LDL cholesterol control by risk category was defined according to South African Guidelines. Multivariable logistic regression models were built to identify factors that were significantly associated with dyslipidemia and awareness of dyslipidemia From 5,059 respondents a total of 4247 subjects (83.9%) had their cholesterol levels measured and were included in our analysis. Overall, 67.3% (2860) of these met criteria for dyslipidemia, only 30 (1.05%) were aware of their condition, and only 21 subjects (0.73%) were on treatment. The majority have abnormalities in triglycerides (59.3%). As cardiovascular risk increased the rates of lipid control according to LDL level dropped. Multivariate logistic regression analyses showed that being overweight was predictive of dyslipidemia (OR 1.76; 95%CI 1.51-2.05, p<0.001) and dyslipidemia awareness (OR 2.58; 95%CI 1.19-5.58; p = 0.017). In conclusion, the very low awareness and treatment of dyslipidemia in this cohort indicate a greater need for systematic screening and education within the population and demonstrate that there are multiple opportunities to allay this burden.

Novel circulating lipid measurements for current dyslipidemias in non-treated patients undergoing coronary angiography: PCSK9, apoC3 and sdLDL-C.

PubMed

Li, Sha; Zhao, Xi; Zhang, Yan; Zhu, Cheng-Gang; Guo, Yuan-Lin; Wu, Na-Qiong; Xu, Rui-Xia; Qing, Ping; Gao, Ying; Sun, Jing; Liu, Geng; Dong, Qian; Li, Jian-Jun

2017-02-14

Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein C-III (apoC3) and small dense low density lipoprotein cholesterol (sdLDL-C), have been recently recognized as circulating atherosclerosis-related lipid measurements. We aimed to elucidate their associations with current dyslipidemias, and identify their levels at increased risk to dyslipidemia. A total of 1,605 consecutive, non-treated patients undergoing diagnostic/interventional coronary angiography were examined. Plasma PCSK9 and apoC3 levels were determined using a validated ELISA assay, and sdLDL-C was measured by the Lipoprint LDL System. Plasma levels of PCSK9, apoC3, and sdLDL-C were associated with the current dyslipidemias classification (all p<0.001). PCSK9 significantly conferred prediction of both hypercholesterolemia and combined hyperlipidemia at a level of 235 ng/ml; apoC3 levels for hypertriglyceridemia, hypercholesterolemia and combined hyperlipidemia were 80.0, 71.5, and 86.4 μg/ml, respectively; and sdLDL-C for hypertriglyceridemia, hypercholesterolemia, combined hyperlipidemia and hypo high density lipoprotein (HDL) cholesterolemia 3.5, 2.5, 4.5, and 2.5 mg/dl, respectively (all p<0.001 for area under the receiver-operating characteristic curve). In a polytomous logistic model comparing increasing LDL-C categories, the interactions with high PCSK9, apoC3, and sdLDL-C elevated gradually. Similarly, apoC3 and sdLDL-C showed elevated interaction with increased triglyceride categories, and only sdLDL-C showed interaction with decreased HDL cholesterol (HDL-C) categories. Furthermore, discordances of PCSK9, apoC3, and sdLDL-C with current dyslipidemias were observed. PCSK9, apoC3, and sdLDL-C showed significant interactions with current dyslipidemias, and were predictive in the screening. The substantial discordances with current dyslipidemias might provide novel view in lipid management and further cardiovascular benefit.

Novel circulating lipid measurements for current dyslipidemias in non-treated patients undergoing coronary angiography: PCSK9, apoC3 and sdLDL-C

PubMed Central

Li, Sha; Zhao, Xi; Zhang, Yan; Zhu, Cheng-Gang; Guo, Yuan-Lin; Wu, Na-Qiong; Xu, Rui-Xia; Qing, Ping; Gao, Ying; Sun, Jing; Liu, Geng; Dong, Qian; Li, Jian-Jun

2017-01-01

Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein C-III (apoC3) and small dense low density lipoprotein cholesterol (sdLDL-C), have been recently recognized as circulating atherosclerosis-related lipid measurements. We aimed to elucidate their associations with current dyslipidemias, and identify their levels at increased risk to dyslipidemia. A total of 1,605 consecutive, non-treated patients undergoing diagnostic/interventional coronary angiography were examined. Plasma PCSK9 and apoC3 levels were determined using a validated ELISA assay, and sdLDL-C was measured by the Lipoprint LDL System. Plasma levels of PCSK9, apoC3, and sdLDL-C were associated with the current dyslipidemias classification (all p<0.001). PCSK9 significantly conferred prediction of both hypercholesterolemia and combined hyperlipidemia at a level of 235 ng/ml; apoC3 levels for hypertriglyceridemia, hypercholesterolemia and combined hyperlipidemia were 80.0, 71.5, and 86.4 g/ml, respectively; and sdLDL-C for hypertriglyceridemia, hypercholesterolemia, combined hyperlipidemia and hypo high density lipoprotein (HDL) cholesterolemia 3.5, 2.5, 4.5, and 2.5 mg/dl, respectively (all p<0.001 for area under the receiver-operating characteristic curve). In a polytomous logistic model comparing increasing LDL-C categories, the interactions with high PCSK9, apoC3, and sdLDL-C elevated gradually. Similarly, apoC3 and sdLDL-C showed elevated interaction with increased triglyceride categories, and only sdLDL-C showed interaction with decreased HDL cholesterol (HDL-C) categories. Furthermore, discordances of PCSK9, apoC3, and sdLDL-C with current dyslipidemias were observed. PCSK9, apoC3, and sdLDL-C showed significant interactions with current dyslipidemias, and were predictive in the screening. The substantial discordances with current dyslipidemias might provide novel view in lipid management and further cardiovascular benefit. PMID:27713142

Status of dyslipidemia treatment in Japanese adults: an analysis of the 2009 Japan Society of Ningen Dock database.

PubMed

Takahashi, Eiko; Moriyama, Kengo; Yamakado, Minoru

2013-01-01

The Japan Atherosclerosis Society (JAS) has recommended serum lipid management goals (SLMGs) based on the coronary heart disease (CHD) risk classification included in its 2007 guidelines for the diagnosis and prevention of atherosclerotic cardiovascular disease in the Japanese population (JAS GL 2007). The Japan Society of Ningen Dock created a database of subjects receiving annual health examinations at 21 institutes nationwide. Using this database, we evaluated the efficacy of current treatment for patients with dyslipidemia by identifying risk factors for CHD development, based on the JAS recommendations. This multicenter, retrospective study was conducted using data obtained from 21 institutions across Japan. 17,991 adults taking dyslipidemia medications were enrolled. The JAS GL 2007 was used for evaluation. Since the guideline indicated separate goals (secondary prevention for subjects with a prior history of CHD and primary prevention for those with other CHD risk factors), we evaluated the percentages of goals met. The serum low-density lipoprotein cholesterol (LDL-C) levels were calculated using the Friedewald formula. The LDL-C level was measured using a direct homogeneous assay if the triglycerides (TG) level was 400 mg/dL or higher. The achievement rates of the SLMGs were as follows: LDL-C, 72.3%; high-density lipoprotein cholesterol (HDL-C), 94.6%; and TG, 69.7%. Our results regarding Japanese patients receiving dyslipidemia treatment for CHD prevention identified insufficient reductions in the levels of LDL-C and TG in those at high risk for CHD and suggest the need for more aggressive lipid-lowering therapy.

Effect of Abdominoplasty in the Lipid Profile of Patients with Dyslipidemia

PubMed Central

Ramos-Gallardo, Guillermo; Pérez Verdin, Ana; Fuentes, Miguel; Godínez Gutiérrez, Sergio; Ambriz-Plascencia, Ana Rosa; González-García, Ignacio; Gómez-Fonseca, Sonia Mericia; Madrigal, Rosalio; González-Reynoso, Luis Iván; Figueroa, Sandra; Toscano Igartua, Xavier; Jiménez Gutierrez, Déctor Francisco

2013-01-01

Introduction. Dyslipidemia like other chronic degenerative diseases is pandemic in Latin America and around the world. A lot of patients asking for body contouring surgery can be sick without knowing it. Objective. Observe the lipid profile of patients with dyslipidemia, before and three months after an abdominoplasty. Methods. Patients candidate to an abdominoplasty without morbid obesity were followed before and three months after the surgery. We compared the lipid profile, glucose, insulin, and HOMA (cardiovascular risk marker) before and three months after the surgery. We used Student's t test to compare the results. A P value less than 0.05 was considered as significant. Results. Twenty-six patients were observed before and after the surgery. At the third month, we found only statistical differences in LDL and triglyceride values (P 0.04 and P 0.03). The rest of metabolic values did not reach statistical significance. Conclusion. In this group of patients with dyslipidemia, at the third month, only LDL and triglyceride values reached statistical significances. There is no significant change in glucose, insulin, HOMA, cholesterol, VLDL, or HDL. PMID:23956856

Dyslipidemia, Hypertension and Diabetes Metaflammation. A Unique Mechanism for 3 Risk Factors.

PubMed

Morales-Villegas, E

2014-07-01

The main current threat to the human race is the correlation and synergy between two determining triumvirates of atherosclerosis, cardiovascular disease and death. The first triumvirate is constituted by obesity, metaflammation and insulin resistance; the second triumvirate is constituted by atherogenic dyslipidemia, hypertension and type 2 diabetes mellitus. The etiopathogenic driving force for both triumvirates is the global epidemic of obesity. Metaflammation and insulin resistance are associated with obesity; in turn, insulin resistance determines a high risk for the development of atherogenic dyslipidemia, hypertension and type 2 diabetes mellitus, the three of them being factors responsible for vascular endothelial injury and substrates involved in the genesis of atherosclerosis, cardiovascular disease and death. The present chapter will address both triumvirates. Firstly, the current concepts of obesity, metaflammation and insulin resistance will be reviewed; emphasizing the second (metaflammation) for being a concept that has revolutionized and integrated our understanding of the harmful effects of obesity. Secondly, the impact of insulin resistance in the regulation of intermediary metabolism and endothelial function will be addressed; this will facilitate the understanding of the inextricable link between atherogenic dyslipidemia, hypertension and type 2 diabetes mellitus. Thus, this chapter aims to present to the clinician the best knowledge to link epidemics of obesity and cardiovascular death, through the sequence of metaflammation, insulin resistance and cardiovascular risk factors (mixed dyslipidemia, hypertension and type 2 diabetes mellitus).

Prevalence of dyslipidemia and its control in type 2 diabetes: A multicenter study in endocrinology clinics of China.

PubMed

Yan, Li; Xu, Ming Tong; Yuan, Li; Chen, Bing; Xu, Zhang Rong; Guo, Qing Hua; Li, Qiang; Duan, Yu; Huang Fu, Jian; Wang, Yong Jian; Zhang, Miao; Luo, Zuo Jie; Zhao, Wei Gang; Wang, You Min; Yuan, Zhen Fang; Wang, Wei Qing; Wang, Peng Hua; Ran, Xing Wu; Wang, Yan Jun; Yang, Hua Zhang; Gao, Ling; Chen, Wei Qing; Ning, Guang

2016-01-01

The aim of this study was to assess the levels of serum lipid and awareness, treatment, and control of dyslipidemia in type 2 diabetes mellitus (T2DM) patients from top-ranked endocrinology clinics in large cities of China. A cross-sectional study in a representative sample of 4807 Chinese adults 40 to 75 years of age was conducted during 2010 to 2011 at 20 endocrinology clinics in top-ranked hospitals covering most of the major cities of China. Serum lipid levels were measured, and treatment of dyslipidemia was recorded and assessed. In the present study, the prevalence of dyslipidemia was 67.1% in T2DM subjects. Among those with dyslipidemia, the proportion of awareness and treatment was 68.7% and 55.9%. Among participants with lipid-lowering therapy, 686 subjects achieved the low-density lipoprotein cholesterol (LDL-C) control less than 2.60 mmol/L, with the rate being 39.4%. In those patients with previous cardiovascular disease, the percentage of participants who achieved LDL-C goal (1.80 mmol/L) was 15.3%. The prevalence of dyslipidemia is high, and the awareness, treatment, and control of dyslipidemia are relatively low in Chinese T2DM patients. This calls for the awareness and intervention of dyslipidemia in these patients. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

The proportion of dyslipidemia in systemic lupus erythematosus patient and distribution of correlated factors.

PubMed

Wijaya, Linda K; Kasjmir, Yoga Iwanoff; Sukmana, Nanang; Subekti, Imam; Prihartono, Joedo

2005-01-01

To understand the proportion of dyslipidemia in systemic lupus erythematosus (SLE) patients and the influencing factors of dyslipidemia. AN observational, cross-sectional study was conducted on new and longstanding SLE patients who had been diagnosed based on ARA criteria 1982 with 1997 revision. They had been hospitalized and treated at Department of Internal Medicine, Cipto Mangunkusumo National Central General Hospital and the other private Hospitals in Jakarta, i.e. Kramat Hospital in July - November 2003. The sample was selected by non probability sampling method with consecutive sampling technique. Every participant underwent history taking, physical and laboratory examination. There were 77 patients satisfying the inclusion criteria. The proportion of dyslipidemia in this study was 75.3%. By confidence interval of 95%, the dyslipidemia in SLE patient was 65.3% - 84.6%. The distribution of lipid profile in sample population were 43% with total cholesterol > or = 200 mg/dL, 26% with HDL cholesterol level < 40 mg/dL, 26.4% with LDL cholesterol level > or = 130 mg/dl and 44.2% with triglycerides serum level > or = 150 mg/dL. The characteristics of influencing factors in dyslipidemia prevalence for sample population consisted of 24.7% with renal involvement, 53.2% with > or = 3 years illness periods, 26% had received > or = 30 mg/day prednisone, 94.8% had not received chloroquines, and 58.4% had illness activity of Mex-SLEDAI > or = 2. By bivariate analysis, we found that illness period < 3 years tends to affect dyslipidemia with OR value of 12.04 (CI 95%, 2.54-57.05, p = 0.001). After conducting multivariate analysis by backward methods, it appears that only one significant influencing factor of dyslipidemia prevalence in SLE patient i.e. Illness period od < 3 years with OR value 12.04 (CI 95% 2.54 - 57.05, p = 0.001). Illness period of 3 years is represent a significant correlative factor for dyslipedemia prevalence. Prednisone > or = 30 mg/dL is the

Atorvastatin Combined Nitroglycerin Therapy Confer Additive Effects on Rabbits with Dyslipidemia.

PubMed

Yang, Fang; Wang, Jindong; Li, Fei; Cui, Lei

2016-06-01

Endogenous nitric oxide (NO) is beneficial for inhibiting Rho-associated kinase 2 (ROCK2) expression. However, the effect of exogenous NO on ROCK2 expression is less investigated. Rabbits with dyslipidemia were produced and randomly assigned into untreated, atorvastatin, nitroglycerin and combined groups (n=10 in each group). Medication therapy was lasted for 2 weeks. Parameters of interest including lipid profiles, liver enzyme, C-reactive protein (CRP), malondialdehyde (MDA), NO level and ROCK2 level were assessed at baseline, 2 weeks of dyslipidemia establishment and 2 weeks of medication treatment. No significant difference in parameters was found between groups at baseline. With 2 weeks of dyslipidemia establishment, as compared to baseline, serum levels of lipid profiles, CRP and MDA were profoundly elevated. In addition, reduced NO generation and enhanced ROCK2 expression were also observed. With 2 weeks of medication therapy, lipid profiles, systemic inflammation (reflected as serum CRP level) and oxidation (reflected as serum MDA level) were improved in the atorvastatin and combined groups but not in the nitroglycerin group (P<0.05). Furthermore, increased NO production in accompany with reduced ROCK2 expression were observed in both the atorvastatin and nitroglycerin groups, and these benefits were further enhanced by combined therapy (P<0.05). No liver enzymes elevation was observed after 2 weeks of medication therapy. Nitroglycerin-derived exogenous NO could effectively inhibit ROCK2 expression in rabbits with dyslipidemia which is independent of lipid-modification, and these efficacies could be enhanced by statins therapy. © Georg Thieme Verlag KG Stuttgart · New York.

Low Urinary Iodine Concentrations Associated with Dyslipidemia in US Adults.

PubMed

Lee, Kyung Won; Shin, Dayeon; Song, Won O

2016-03-17

Iodine is an essential component of the thyroid hormone which plays crucial roles in healthy thyroid function and lipid metabolism. However, the association between iodine status and dyslipidemia has not been well established at a population level. We aimed to test the hypothesis that the odds of dyslipidemia including elevated total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol and apolipoprotein B, and lowered high-density lipoprotein (HDL) cholesterol and HDL/LDL ratio are associated with urinary iodine concentration (UIC) in a population perspective. Data of 2495 US adults (≥20 years) in the National Health and Nutrition Examination Survey 2007-2012 were used in this study. Two subgroups (i.e., UIC below vs. above the 10th percentile) were compared of dyslipidemia as defined based on NCEP ATP III guidelines. The differences between the groups were tested statistically by chi-square test, simple linear regressions, and multiple logistic regressions. Serum lipid concentrations differed significantly between two iodine status groups when sociodemographic and lifestyle covariates were controlled (all, p < 0.05). Those with the lowest decile of UIC were more likely to be at risk for elevated total cholesterol (>200 mg/dL) (adjusted odds ratio (AOR) = 1.51, 95% confidence interval (CI): 1.03-2.23) and elevated LDL cholesterol (>130 mg/dL) (AOR = 1.58, 95% CI: 1.11-2.23) and lowered HDL/LDL ratio (<0.4) (AOR = 1.66, 95% CI: 1.18-2.33), compared to those with UIC above the 10th percentile. In US adults, low UIC was associated with increased odds for dyslipidemia. Findings of the present cross-sectional study with spot urine samples highlight the significant association between UIC and serum lipids at population level, but do not substantiate a causal relationship. Further investigations are warranted to elucidate the causal relationship among iodine intakes, iodine status, and serum lipid profiles.

Association Between Physical Therapy and Risk of Coronary Artery Disease and Dyslipidemia Among Osteoarthritis Patients: A Nationwide Database Study.

PubMed

Yeh, Huan-Jui; Chou, Yiing-Jenq; Yang, Nan-Ping; Cheng, Chi-Chia; Huang, Nicole

2016-01-01

To provide empirical evidence on the effect of early physical therapy (PT) within the first year of osteoarthritis (OA) diagnosis on reduction in OA-related comorbidities in patients with OA. Retrospective cohort study. The study was conducted using a nationally representative sample of 1 million National Health Insurance enrollees. Newly diagnosed patients with OA (N=13,545). One-to-one propensity score matching was used to match patients who received PT within the first year of OA diagnosis (PT group; n=3403) with an equal number of patients with OA who did not receive PT (non-PT group). Not applicable. The 4-year cumulative risk of comorbidities including coronary artery disease (CAD), diabetes mellitus, dyslipidemia, osteoporosis, gastrointestinal tract ulcer, and renal failure was estimated. A Cox proportional hazards regression analysis was performed to identify the dose-response relation between the PT dosage and the risk of OA-related comorbidities. A total of 3403 patients (25.1%) received PT within the first year of OA diagnosis. The PT group had a significantly lower 4-year cumulative risk of dyslipidemia (P=.05) and a potentially lower 4-year cumulative risk of CAD (P=.09). After adjusting for other potential confounders, the Cox proportional hazards regression analysis showed that patients with OA who received a high PT dosage had a low risk of CAD and dyslipidemia. Patients with OA who received PT had a lower risk of OA-related comorbidities such as dyslipidemia or CAD. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Improved multiplex ligation-dependent probe amplification analysis identifies a deleterious PMS2 allele generated by recombination with crossover between PMS2 and PMS2CL.

PubMed

Wernstedt, Annekatrin; Valtorta, Emanuele; Armelao, Franco; Togni, Roberto; Girlando, Salvatore; Baudis, Michael; Heinimann, Karl; Messiaen, Ludwine; Staehli, Noemie; Zschocke, Johannes; Marra, Giancarlo; Wimmer, Katharina

2012-09-01

Heterozygous PMS2 germline mutations are associated with Lynch syndrome. Up to one third of these mutations are genomic deletions. Their detection is complicated by a pseudogene (PMS2CL), which--owing to extensive interparalog sequence exchange--closely resembles PMS2 downstream of exon 12. A recently redesigned multiplex ligation-dependent probe amplification (MLPA) assay identifies PMS2 copy number alterations with improved reliability when used with reference DNAs containing equal numbers of PMS2- and PMS2CL-specific sequences. We selected eight such reference samples--all publicly available--and used them with this assay to study 13 patients with PMS2-defective colorectal tumors. Three presented deleterious alterations: an Alu-mediated exon deletion; a 125-kb deletion encompassing PMS2 and four additional genes (two with tumor-suppressing functions); and a novel deleterious hybrid PMS2 allele produced by recombination with crossover between PMS2 and PMS2CL, with the breakpoint in intron 10 (the most 5' breakpoint of its kind reported thus far). We discuss mechanisms that might generate this allele in different chromosomal configurations (and their diagnostic implications) and describe an allele-specific PCR assay that facilitates its detection. Our data indicate that the redesigned PMS2 MLPA assay is a valid first-line option. In our series, it identified roughly a quarter of all PMS2 mutations. Copyright © 2012 Wiley Periodicals, Inc.

DRD4 dopamine receptor allelic diversity in various primate species

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adamson, M.; Higley, D.; O`Brien, S.

The DRD4 dopamine receptor is uniquely characterized by a 48 bp repeating segment within the coding region, located in exon III. Different DRD4 alleles are produced by the presence of additional 48 bp repeats, each of which adds 16 amino acids to the length of the 3rd intracytoplasmic loop of the receptor. The DRD4 receptor is therefore an intriguing candidate gene for behaviors which are influenced by dopamine function. In several human populations, DRD4 alleles with 2-8 and 10 repeats have previously been identified, and the 4 and 7 repeat alleles are the most abundant. We have determined DRD4 genotypesmore » in the following nonhuman primate species: chimpanzee N=2, pygmy chimpanzee N=2, gorilla N=4, siamang N=2, Gelada baboon N=1, gibbon N=1, orangutan (Bornean and Sumatran) N=62, spider monkey N=4, owl monkey N=1, Colobus monkey N=1, Patas monkey N=1, ruffed lemur N=1, rhesus macaque N=8, and vervet monkey N=28. The degree of DRD4 polymorphism and which DRD4 alleles were present both showed considerable variation across primate species. In contrast to the human, rhesus macaque monkeys were monomorphic. The 4 and 7 repeat allels, highly abundant in the human, may not be present in certain other primates. For example, the four spider monkeys we studied showed the 7, 8 and 9 repeat length alleles and the only gibbon we analyzed was homozygous for the 9 repeat allele (thus far not observed in the human). Genotyping of other primate species and sequencing of the individual DRD4 repeat alleles in different species may help us determine the ancestral DRD4 repeat length and identify connections between DRD4 genotype and phenotype.« less

Risk factors associated with atherogenic dyslipidemia in the presence of optimal statin therapy.

PubMed

Zhao, Wang; Zheng, Xi-Long; Jiang, Ze-Nan; Liao, Xiao-Bo; Zhao, Shui-Ping

2017-12-01

This study investigated the prevalence of atherogenic dyslipidemia (AD) in Chinese outpatients whose low-density lipoprotein cholesterol (LDL-C) levels reached the goals with statin monotherapy and evaluated the characteristics of these patients. An analysis of the Dyslipidemia International Survey-China study that was carried out at 122 hospitals in China. Among patients reaching their LDL-C goals, the presence of AD was defined as triglyceride levels ≥1.7mmol/L and/or low levels of high-density lipoprotein cholesterol (men: <1.0mmol/L; women: <1.3mmol/L). 22,039 patients receiving statin monotherapy were analyzed. According to the American National Cholesterol Education Program Adult Treatment Panel III, 13,088 patients reached LDL-C goals, and 7134 patients of them had AD. Age, male gender, BMI, sedentary lifestyle, diabetes mellitus, ischemic cerebrovascular disease, serum uric acid levels, and fasting plasma glucose (all P<0.05) were independently associated with AD. Based on the Chinese guideline for the management of dyslipidemia, 13,551 patients reached LDL-C goals, and 7719 patients of them had AD. Age, male gender, BMI, sedentary lifestyle, coronary heart disease, serum uric acid levels, and fasting plasma glucose (all P<0.05) were independently associated with AD. The intensity of statin therapy did not affect the prevalence of AD. There was a high prevalence of AD in Chinese patients with optimal statin treatment. Some risk factors associated with AD were identified, but these factors were slightly different according to two criteria/guidelines. The intensity of statin therapy did not reduce the prevalence of AD. A combination lipid therapy may be more suitable for Chinese patients. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

A predisposition for allergies predicts subsequent hypertension, dyslipidemia, and diabetes mellitus among patients with schizophrenia or bipolar disorder: a nationwide longitudinal study.

PubMed

Chen, Mu-Hong; Li, Cheng-Ta; Lin, Wei-Chen; Wei, Hang-Tin; Chang, Wen-Han; Chen, Tzeng-Ji; Pan, Tai-Long; Su, Tung-Ping; Bai, Ya-Mei

2014-10-01

Previous studies have shown that both severe mental disorders (schizophrenia and bipolar disorder) and atopic diseases were associated with an increased risk of metabolic syndrome. However, the role of atopy/the predisposition for allergies in the development of metabolic syndrome is still unknown among those with severe mental disorders. Using the Taiwan National Health Insurance Research Database, 5826 patients with schizophrenia or bipolar disorder (1908 with a predisposition for allergies and 3918 without) were enrolled between 1998 and 2008. Those who developed hypertension, dyslipidemia, and/or diabetes mellitus were identified during the follow-up to the end of 2011. A predisposition for allergies increased the risk of developing hypertension (HR: 1.67), dyslipidemia (HR: 1.82), and diabetes mellitus (HR: 1.37) in later life among those with severe mental disorders. A dose-dependent relationship was noted between having more atopic comorbidities and a greater likelihood of hypertension (1 atopic disease: HR: 1.60; ≧ 2 atopic comorbidities: HR: 1.87), dyslipidemia (HR: 1.73; HR: 2.12), and diabetes mellitus (HR: 1.26; HR: 1.69). A predisposition for allergies was an independent risk factor for hypertension, dyslipidemia, and diabetes mellitus among patients with schizophrenia or bipolar disorder. Further studies would be required to elucidate the underlying pathophysiology among atopy, schizophrenia, bipolar disorder, and metabolic syndrome. Copyright © 2014 Elsevier B.V. All rights reserved.

Influence of route of administration/drug formulation and other factors on adherence to treatment in rheumatoid arthritis (pain related) and dyslipidemia (non-pain related).

PubMed

Fautrel, Bruno; Balsa, Alejandro; Van Riel, Piet; Casillas, Marta; Capron, Jean-Philippe; Cueille, Carine; de la Torre, Inmaculada

2017-07-01

A comprehensive review was performed to investigate the effect of route of administration on medication adherence and persistence in rheumatoid arthritis (RA) and to compare adherence/persistence with oral medications between RA and a non-painful disease (dyslipidemia). Comprehensive database searches were performed to identify studies investigating medication adherence and/or persistence in adults with RA receiving conventional synthetic or biologic agents. Similar searches were performed for studies of patients with dyslipidemia receiving statins. Studies had to be published after 1998 in English and involve ≥6 months' follow up. Adherence and persistence were compared between the different routes of drug administration in RA, and between the two diseases for oral medications. A total of 35 and 28 papers underwent data extraction for RA and dyslipidemia, respectively. Within the constraints of the analysis, adherence and persistence rates appeared broadly similar for the different routes of drug administration in RA. Adherence to oral medications was also broadly similar across the two diseases, but persistence was lower in dyslipidemia. Poor adherence has clinical consequences in both diseases: greater disease activity and risk of flare in RA, and increased serum cholesterol levels and risk of heart and cerebrovascular disease in dyslipidemia. Over 1-3 years, poor adherence to biologic RA medications led to increased resource use and medical costs but lower total direct costs due to reduced biologic drug costs. Conversely, poor adherence to dyslipidemia medications resulted in increased total direct costs. In both diseases, adherence improved with patient education/support. The route of drug administration and the symptomatic (pain) nature of the disease do not appear to be dominant factors for drug adherence or persistence in RA. The wide range of adherence and persistence values and definitions across studies made comparisons between drug formulations and

Allele-specific Characterization of Alanine: Glyoxylate Aminotransferase Variants Associated with Primary Hyperoxaluria

PubMed Central

Lage, Melissa D.; Pittman, Adrianne M. C.; Roncador, Alessandro; Cellini, Barbara; Tucker, Chandra L.

2014-01-01

Primary Hyperoxaluria Type 1 (PH1) is a rare autosomal recessive kidney stone disease caused by deficiency of the peroxisomal enzyme alanine: glyoxylate aminotransferase (AGT), which is involved in glyoxylate detoxification. Over 75 different missense mutations in AGT have been found associated with PH1. While some of the mutations have been found to affect enzyme activity, stability, and/or localization, approximately half of these mutations are completely uncharacterized. In this study, we sought to systematically characterize AGT missense mutations associated with PH1. To facilitate analysis, we used two high-throughput yeast-based assays: one that assesses AGT specific activity, and one that assesses protein stability. Approximately 30% of PH1-associated missense mutations are found in conjunction with a minor allele polymorphic variant, which can interact to elicit complex effects on protein stability and trafficking. To better understand this allele interaction, we functionally characterized each of 34 mutants on both the major (wild-type) and minor allele backgrounds, identifying mutations that synergize with the minor allele. We classify these mutants into four distinct categories depending on activity/stability results in the different alleles. Twelve mutants were found to display reduced activity in combination with the minor allele, compared with the major allele background. When mapped on the AGT dimer structure, these mutants reveal localized regions of the protein that appear particularly sensitive to interactions with the minor allele variant. While the majority of the deleterious effects on activity in the minor allele can be attributed to synergistic interaction affecting protein stability, we identify one mutation, E274D, that appears to specifically affect activity when in combination with the minor allele. PMID:24718375

[Awareness rate, treatment rate and control rate of dyslipidemia in Chinese adults, 2010].

PubMed

Li, Jian-hong; Wang, Li-min; Mi, Sheng-quan; Zhang, Mei; Li, Yi-chong; Jiang, Yong; Xu, Yu; Dai, Meng; Wang, Lin-hong

2012-08-01

To explore the awareness, treatment and control rates of dyslipidemia among Chinese adults aged over 18 in 2010, and to analyze the prevalent features. 97 409 subjects aged over 18 were recruited from 162 monitoring sites around 31 provinces in China mainland in 2010, applying multi-stage stratified cluster random sampling method. Information about subjects' history of dyslipidemia, treatment and control were collected by face-to-face interview; and each subject's fasting venous blood was drawn in the morning before having food, to test total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C). In total, 51 818 cases of dyslipidemia ever or now, including 2235 subjects who once suffered from dyslipidemia but had their blood lipid controlled to normal, were screened out. And the awareness, treatment and control rates were calculated by complex weighting. The awareness rate of dyslipidemia among Chinese adults was 10.93%, while the stratified rates were 6.00%, 16.75% and 18.74% in the groups of subjects aged 18 - 44, 45 - 59 and over 60 years old, respectively (χ² = 1293.02, P < 0.01); 10.32% and 11.71% among males and females, respectively (χ² = 18.67, P < 0.01); 16.59% and 8.17% in groups from urban and rural areas, respectively (χ² = 618.38, P < 0.01); and 12.22%, 11.75% and 8.26% in groups from eastern, central and western China, respectively (χ² = 117.04, P < 0.01). The treatment rate of dyslipidemia was 6.84% among Chinese adults, while the stratified rates were 3.55%, 10.73% and 12.05% in the groups of subjects aged 18 - 44, 45 - 59 and over 60 years old, respectively (χ² = 858.72, P < 0.01); 6.37% and 7.43% among males and females, respectively (χ² = 16.69, P < 0.01); 10.17% and 5.21% in groups from urban and rural areas, respectively (χ² = 327.51, P < 0.01); and 7.33%, 7.52% and 5.41% in groups from eastern, central and western China, respectively (χ² = 50.71, P < 0

Maize ARGOS1 (ZAR1) transgenic alleles increase hybrid maize yield.

PubMed

Guo, Mei; Rupe, Mary A; Wei, Jun; Winkler, Chris; Goncalves-Butruille, Marymar; Weers, Ben P; Cerwick, Sharon F; Dieter, Jo Ann; Duncan, Keith E; Howard, Richard J; Hou, Zhenglin; Löffler, Carlos M; Cooper, Mark; Simmons, Carl R

2014-01-01

Crop improvement for yield and drought tolerance is challenging due to the complex genetic nature of these traits and environmental dependencies. This study reports that transgenic over-expression of Zea mays AR GOS1 (ZAR1) enhanced maize organ growth, grain yield, and drought-stress tolerance. The ZAR1 transgene exhibited environmental interactions, with yield increase under Temperate Dry and yield reduction under Temperate Humid or High Latitude environments. Native ZAR1 allele variation associated with drought-stress tolerance. Two founder alleles identified in the mid-maturity germplasm of North America now predominate in Pioneer's modern breeding programme, and have distinct proteins, promoters and expression patterns. These two major alleles show heterotic group partitioning, with one predominant in Pioneer's female and the other in the male heterotic groups, respectively. These two alleles also associate with favourable crop performance when heterozygous. Allele-specific transgene testing showed that, of the two alleles discussed here, each allele differed in their impact on yield and environmental interactions. Moreover, when transgenically stacked together the allelic pair showed yield and environmental performance advantages over either single allele, resembling heterosis effects. This work demonstrates differences in transgenic efficacy of native alleles and the differences reflect their association with hybrid breeding performance.

Maize ARGOS1 (ZAR1) transgenic alleles increase hybrid maize yield

PubMed Central

Guo, Mei

2014-01-01

Crop improvement for yield and drought tolerance is challenging due to the complex genetic nature of these traits and environmental dependencies. This study reports that transgenic over-expression of Zea mays ARGOS1 (ZAR1) enhanced maize organ growth, grain yield, and drought-stress tolerance. The ZAR1 transgene exhibited environmental interactions, with yield increase under Temperate Dry and yield reduction under Temperate Humid or High Latitude environments. Native ZAR1 allele variation associated with drought-stress tolerance. Two founder alleles identified in the mid-maturity germplasm of North America now predominate in Pioneer’s modern breeding programme, and have distinct proteins, promoters and expression patterns. These two major alleles show heterotic group partitioning, with one predominant in Pioneer’s female and the other in the male heterotic groups, respectively. These two alleles also associate with favourable crop performance when heterozygous. Allele-specific transgene testing showed that, of the two alleles discussed here, each allele differed in their impact on yield and environmental interactions. Moreover, when transgenically stacked together the allelic pair showed yield and environmental performance advantages over either single allele, resembling heterosis effects. This work demonstrates differences in transgenic efficacy of native alleles and the differences reflect their association with hybrid breeding performance. PMID:24218327

[The impaired glucose tolerance in the pathogenesis of dyslipidemia].

PubMed

Ikoue, I; Takahashi, K; Katayama, S

1996-10-01

It is well known that hyperlipidemia is often present in patient with impaired glucose tolerance, obesity and/or hypertension. All of these are risk factors for coronary artery disease (CAD). The coexistence of these risk factors markedly increase the likelihood of CAD. Recently, it has been reported that the impaired glucose tolerance and insulin resistence are associated with the increased proinsulin, which is linked to the risk of CAD. We review that the impaired glucose tolerance is an important factor causing dyslipidemia. The characteristic of dyslipidemia associated with the impaired glucose tolerance include hypertriglyceridemia, high level of VLDL and low level of HDL cholesterol. They also associate with accumulation of remnant lipoproteins and appearance of small dense LDL. In addition, we pointed out that the increased number of risk factors is associated with elevated insulin and proinsulin level.

Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus

PubMed Central

Tangvarasittichai, Surapon

2015-01-01

Oxidative stress is increased in metabolic syndrome and type 2 diabetes mellitus (T2DM) and this appears to underlie the development of cardiovascular disease, T2DM and diabetic complications. Increased oxidative stress appears to be a deleterious factor leading to insulin resistance, dyslipidemia, β-cell dysfunction, impaired glucose tolerance and ultimately leading to T2DM. Chronic oxidative stress, hyperglycemia and dyslipidemia are particularly dangerous for β-cells from lowest levels of antioxidant, have high oxidative energy requirements, decrease the gene expression of key β-cell genes and induce cell death. If β-cell functioning is impaired, it results in an under production of insulin, impairs glucose stimulated insulin secretion, fasting hyperglycemia and eventually the development of T2DM. PMID:25897356

Pharmacological Targeting of the Atherogenic Dyslipidemia Complex: The Next Frontier in CVD Prevention Beyond Lowering LDL Cholesterol.

PubMed

Xiao, Changting; Dash, Satya; Morgantini, Cecilia; Hegele, Robert A; Lewis, Gary F

2016-07-01

Notwithstanding the effectiveness of lowering LDL cholesterol, residual CVD risk remains in high-risk populations, including patients with diabetes, likely contributed to by non-LDL lipid abnormalities. In this Perspectives in Diabetes article, we emphasize that changing demographics and lifestyles over the past few decades have resulted in an epidemic of the "atherogenic dyslipidemia complex," the main features of which include hypertriglyceridemia, low HDL cholesterol levels, qualitative changes in LDL particles, accumulation of remnant lipoproteins, and postprandial hyperlipidemia. We briefly review the underlying pathophysiology of this form of dyslipidemia, in particular its association with insulin resistance, obesity, and type 2 diabetes, and the marked atherogenicity of this condition. We explain the failure of existing classes of therapeutic agents such as fibrates, niacin, and cholesteryl ester transfer protein inhibitors that are known to modify components of the atherogenic dyslipidemia complex. Finally, we discuss targeted repurposing of existing therapies and review promising new therapeutic strategies to modify the atherogenic dyslipidemia complex. We postulate that targeting the central abnormality of the atherogenic dyslipidemia complex, the elevation of triglyceride-rich lipoprotein particles, represents a new frontier in CVD prevention and is likely to prove the most effective strategy in correcting most aspects of the atherogenic dyslipidemia complex, thereby preventing CVD events. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Improved Multiplex Ligation-Dependent Probe Amplification Analysis Identifies a Deleterious PMS2 Allele Generated by Recombination with Crossover Between PMS2 and PMS2CL

PubMed Central

Wernstedt, Annekatrin; Valtorta, Emanuele; Armelao, Franco; Togni, Roberto; Girlando, Salvatore; Baudis, Michael; Heinimann, Karl; Messiaen, Ludwine; Staehli, Noemie; Zschocke, Johannes; Marra, Giancarlo; Wimmer, Katharina

2012-01-01

Heterozygous PMS2 germline mutations are associated with Lynch syndrome. Up to one third of these mutations are genomic deletions. Their detection is complicated by a pseudogene (PMS2CL), which – owing to extensive interparalog sequence exchange – closely resembles PMS2 downstream of exon 12. A recently redesigned multiplex ligation-dependent probe amplification (MLPA) assay identifies PMS2 copy number alterations with improved reliability when used with reference DNAs containing equal numbers of PMS2- and PMS2CL-specific sequences. We selected eight such reference samples – all publicly available – and used them with this assay to study 13 patients with PMS2-defective colorectal tumors. Three presented deleterious alterations: an Alu-mediated exon deletion; a 125-kb deletion encompassing PMS2 and four additional genes (two with tumor-suppressing functions); and a novel deleterious hybrid PMS2 allele produced by recombination with crossover between PMS2 and PMS2CL, with the breakpoint in intron 10 (the most 5′ breakpoint of its kind reported thus far). We discuss mechanisms that might generate this allele in different chromosomal configurations (and their diagnostic implications) and describe an allele-specific PCR assay that facilitates its detection. Our data indicate that the redesigned PMS2 MLPA assay is a valid first-line option. In our series, it identified roughly a quarter of all PMS2 mutations. © 2012 Wiley Periodicals, Inc. PMID:22585707

Efficacy of mulberry leaf tablets in patients with mild dyslipidemia.

PubMed

Aramwit, Pornanong; Petcharat, Kanokwan; Supasyndh, Ouppatham

2011-03-01

Mulberry leaf is well known for its several biological effects. The purpose of this study was to evaluate the hypolipidemic effect of mulberry leaf in non-diabetic patients with mild dyslipidemia. A within-subjects research design was conducted at the out-patient clinic in Thailand. Twenty-three patients who met the NCEP ATP III criteria guideline for dyslipidemia and failed a 4 week diet therapy were enrolled and assigned to receive three tablets of 280 mg mulberry leaf tablet three times a day before meals for a period of 12 weeks. Routine blood analyses including lipid parameters and liver function tests were performed every 4 weeks. At 4 and 8 weeks of mulberry leaf tablet therapy, triglyceride was significantly decreased by 10.2% (p < 0.05) and 12.5% (p < 0.05), respectively, from baseline. At the end of the study, total cholesterol, triglyceride and LDL were significantly decreased by 4.9% (p < 0.05), 14.1% (p < 0.05) and 5.6% (p < 0.05), respectively, from baseline, whereas HDL was significantly increased by 19.7% (p < 0.05). Even though some patients experienced side effects such as mild diarrhea (26%), dizziness (8.7%) or constipation and bloating (4.3%), mulberry leaf tablet therapy is still capable and safe in reducing cholesterol levels and enhancing HDL in patients with mild dyslipidemia. Copyright © 2010 John Wiley & Sons, Ltd.

Dyslipidemia and dementia: current epidemiology, genetic evidence and mechanisms behind the associations

PubMed Central

Reitz, Christiane

2013-01-01

The role of cholesterol in the etiology of Alzheimer’s disease (AD) is still controversial. Some studies aiming to explore the association between lipids and/or lipid lowering treatment and AD indicate a harmful effect of dyslipidemia and a beneficial effect of statin therapy on AD risk. The findings are supported by genetic linkage and association studies that have clearly identified several genes involved in cholesterol metabolism or transport as AD susceptibility genes, including Apolipoprotein E (APOE), Apolipoprotein J (APOJ, CLU) and the sortilin-related receptor (SORL1). Functional cell biology studies support a critical involvement of lipid raft cholesterol in the modulation of AbetaPP processing by β- and γ-secretase resulting in altered Aβ production. Contradictory evidence comes from epidemiological studies showing no or controversial association between dyslipidemia and AD risk, cell biology studies suggesting that there is little exchange between circulating and brain cholesterol, that increased membrane cholesterol is protective by inhibiting loss of membrane integrity through amyloid cytotoxicity, and that cellular cholesterol inhibits co-localization of BACE1 and AbetaPP in non-raft membrane domains and thereby increasing generation of plasmin, an Aβ-degrading enzyme. The aim of this review is to summarize the findings of epidemiologic and cell biologic studies aiming to elucidate the role of cholesterol in AD etiology. PMID:21965313

[A 6-year evaluation of dyslipidemia in a health center: Importance of improvement actions].

PubMed

Antón-García, F; Correcher-Salvador, E; Rodríguez-Lagos, F A; González-Caminero, S

2014-01-01

Dyslipidemia, especially an increased LDL-cholesterol, has been shown to be one of the most important risk factors in the genesis of coronary involvement. The prevalence of dyslipidemias in Spain is high. The objective of this study is to assess the progress of dyslipidemic patients in our health center over a 6-year period, and see if there has been any improvement in its control after the presentation of the evaluation of the first 3 years, as well as an updated dyslipidemia protocol. Assessment Period 1 (2006-2008): 267 patients with dyslipidemia. Assessment Period 2 (2009-2011): 222 patients, excluding exitus and address changes. age, sex, personal history of CVD, vascular risk factors, lipids, drug treatment, risk levels, and percentages of CV control objectives. Mean age was 66.2 years (SD 13.4), 66.3% women. Period 1-Period 2: Total cholesterol: 221.9-196.6 mg/dl (P=.000); LDL-cholesterol: 147.9-115.8 mg/dl (P=.000). In high risk patients, therapeutic targets: 14-50.5% (P=.024); medium risk: 35-68.1% (P=.038); low risk: 44-68.2% (P=NS). Pharmacotherapy 68-77% (P=.000). Changing treatment: 30-43% (P=.001). Adherence: 75-86% (P=.003). Untreated high risk: 15.4-16.3% (P=NS). There was a significant improvement in Period 2, especially in high-risk patients, after presenting the results of the evaluation for Period 1 and with the updated dyslipidemia protocol. There are high risk patients without lipid-lowering treatment to be detected and reviewed. Copyright © 2013 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

Allelic inhibition of displacement activity: a simplified one tube allele-specific PCR for evaluation of ITPA polymorphisms.

PubMed

Galmozzi, E; Facchetti, F; Degasperi, E; Aghemo, A; Lampertico, P

2013-02-01

Recently, genome-wide association studies (GWAS) in patients with chronic hepatitis C virus (HCV) infection have identified two functional single nucleotide polymorphisms (SNPs) in the inosine triphosphatase (ITPA) gene, that are associated strongly and independently with hemolytic anemia in patients exposed to pegylated-interferon (Peg-IFN) plus ribavirin (RBV) combined therapy. Here has been developed a simplified allele discrimination polymerase chain reaction (PCR) assay named allelic inhibition of displacement activity (AIDA) for evaluation of ITPA polymorphisms. AIDA system relies on three unlabeled primers only, two outer common primers and one inner primer with allele-specific 3' terminus mismatch. DNA samples from 192 patients with chronic HCV infection were used to validate the AIDA system and results were compared with the gold standard TaqMan(®) SNP genotyping assay. Concordant data were obtained for all samples, granting for high specificity of the method. In conclusion, AIDA is a practical one-tube method to reproducibly and to assess accurately rs7270101 and rs1127354 ITPA SNPs. Copyright © 2012 Elsevier B.V. All rights reserved.

Gender and urban-rural difference in anthropometric indices predicting dyslipidemia in Chinese primary school children: a cross-sectional study.

PubMed

Zheng, Wei; Zhao, Ai; Xue, Yong; Zheng, Yingdong; Chen, Yun; Mu, Zhishen; Wang, Peiyu; Zhang, Yumei

2016-04-30

Childhood dyslipidemia is a critical factor of lifelong health. Therefore, screening and controlling dyslipidemia from childhood is a practical healthy strategy. However, few studies have examined the performance of anthropometric predictors of dyslipidemia in Chinese children, let alone the potential gender and urban-rural disparity. Thus, we evaluated anthropometric indices predicting dyslipidemia by genders and living areas in Chinese children. Data were from a health and nutrition survey conducted in seven urban areas and two rural areas in China between 2011 and 2012. The serum lipid levels of the participants were compared between genders and living areas. The body mass index z-score (BMI z-score), waist-hip ratio (WHR), waist-height ratio (WHtR), and mid-upper arm height ratio (MaHtR) were used as predictors. The receiver operating characteristic (ROC) analysis was performed to investigate the ability of anthropometric indices predicting dyslipidemia. A total of 773 participants (average age = 9.3 ± 1.7 y) were included. The prevalence of dyslipidemia was 10.9%. Anthropometric indices were all significantly related to blood lipid profiles in boys after adjustment for age. The areas under the ROC curves (ACUs) were significantly larger than 0.5 in boys (ranged between 0.66-0.73), and were larger in rural boys (ranged between 0.68 and 0.94). MaHtR and WHR were associated with the highest specificity (93.8%) and highest sensitivity (100%), respectively. Using anthropometric indices, screening for dyslipidemia may be more appropriate in boys than in girls in China, especially in rural boys. The BMI z-score, WHR, WHtR, and MaHtR were all significantly associated with dyslipidemia in boys; using WHR and MaHtR as indicators achieved the highest sensitivity and specificity, respectively.

Association between ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133), FTO (rs9939609) Genes Polymorphism and Type 2 Diabetes with Dyslipidemia.

PubMed

Raza, Syed Tasleem; Abbas, Shania; Siddiqi, Zeba; Mahdi, Farzana

2017-01-01

Diabetic dyslipidemia is one of the leading causes of coronary artery disease (CAD) death. Genetic and environmental factors play an important role in the development of type 2 diabetes mellitus (T2DM) and dyslipidemia. The present study was aimed to investigate the association of ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133) and FTO (rs9939609) genes polymorphism in T2DM with dyslipidemia. Totally, 559 subjects including 221 T2DM cases with dyslipidemia, 158 T2DM without dyslipidemia and 180 controls were enrolled. ACE genes polymorphism was evaluated by polymerase chain reaction (PCR), while MTHFR , FABP2 , FTO genes polymorphisms were evaluated by PCR and restriction fragment length polymorphism (RFLP). Significant association of ACE and MTHFR genes polymorphisms were found in both group of cases [T2DM with dyslipidemia (P<0.001, and P=0.008, respectively) and T2DM without dyslipidemia (P=0.003, and P=0.010, respectively)] while FABP2 and FTO genes polymorphisms were significantly associated with T2DM without dyslipidemia (P=0.038, and P= 0.019, respectively). This study concludes that ACE , FABP2 , FTO and MTHFR genes are associated with T2DM. Additionally, it also seems that ACE and MTHFR genes might be further associated with the development of dyslipidemia in T2DM cases.

PTEN/MMAC1 Mutations in Hepatocellular Carcinomas: Somatic Inactivation of Both Alleles in Tumors

PubMed Central

Kawamura, Naoki; Nagai, Hisaki; Bando, Koichi; Koyama, Masaaki; Matsumoto, Satoshi; Tajiri, Takashi; Onda, Masahiko; Fujimoto, Jiro; Ueki, Takahiro; Konishi, Noboru; Shiba, Tadayoshi

1999-01-01

Allelic loss of loci on chromosome 10q occurs frequently in hepatocellular carcinomas. Somatic mutations of the PTEN/MMAC1 gene on this chromosome at 10q23 were recently identified in sporadic cancers of the uterus, brain, prostate and breast. To investigate the potential role of PTEN/MMAC1 gene in the genesis of hepatocellular carcinomas, we examined 96 tumors for allelic loss on 10q and also for subtle mutations anywhere within the coding region of PTEN/MMAC1 gene. Allelic loss was identified in 25 of the 89 (27%) tumors that were informative for polymorphic markers in the region. Somatic mutations were identified in five of those tumors: three frameshift mutations, a 1‐bp insertion at codon 83–84 in exon 4 and two 4‐bp deletions, both at codon 318–319 in exon 8; two C‐to‐G transversion mutation, both at ‐9 bp from the initiation codon in the 5’non‐coding region of exon 1. No missense mutation was observed in this panel of tumors. In most of the informative tumors carrying intragenic mutations of one allele, we were able to detect loss of heterozygosity as well. These findings suggest that two alleles of the PTEN/MMAC1 gene may be inactivated by a combination of intragenic point mutation on one allele and loss of chromosomal material on the other allele in some of these tumors. PMID:10363579

Nigerian Honey Ameliorates Hyperglycemia and Dyslipidemia in Alloxan-Induced Diabetic Rats

PubMed Central

Erejuwa, Omotayo O.; Nwobodo, Ndubuisi N.; Akpan, Joseph L.; Okorie, Ugochi A.; Ezeonu, Chinonyelum T.; Ezeokpo, Basil C.; Nwadike, Kenneth I.; Erhiano, Erhirhie; Abdul Wahab, Mohd S.; Sulaiman, Siti A.

2016-01-01

Diabetic dyslipidemia contributes to an increased risk of cardiovascular disease. Hence, its treatment is necessary to reduce cardiovascular events. Honey reduces hyperglycemia and dyslipidemia. The reproducibility of these beneficial effects and their generalization to honey samples of other geographical parts of the world remain controversial. Currently, data are limited and findings are inconclusive especially with evidence showing honey increased glycosylated hemoglobin in diabetic patients. It was hypothesized that this deteriorating effect might be due to administered high doses. This study investigated if Nigerian honey could ameliorate hyperglycemia and hyperlipidemia. It also evaluated if high doses of honey could worsen glucose and lipid abnormalities. Honey (1.0, 2.0 or 3.0 g/kg) was administered to diabetic rats for three weeks. Honey (1.0 or 2.0 g/kg) significantly (p < 0.05) increased high density lipoprotein (HDL) cholesterol while it significantly (p < 0.05) reduced hyperglycemia, triglycerides (TGs), very low density lipoprotein (VLDL) cholesterol, non-HDL cholesterol, coronary risk index (CRI) and cardiovascular risk index (CVRI). In contrast, honey (3.0 g/kg) significantly (p < 0.05) reduced TGs and VLDL cholesterol. This study confirms the reproducibility of glucose lowering and hypolipidemic effects of honey using Nigerian honey. However, none of the doses deteriorated hyperglycemia and dyslipidemia. PMID:26927161

Identification of the third/extra allele for forensic application in cases with TPOX tri-allelic pattern.

PubMed

Picanço, Juliane Bentes; Raimann, Paulo Eduardo; Motta, Carlos Henrique Ares Silveira da; Rodenbusch, Rodrigo; Gusmão, Leonor; Alho, Clarice Sampaio

2015-05-01

Genotyping of polymorphic short tandem repeats (STRs) loci is widely used in forensic DNA analysis. STR loci eventually present tri-allelic pattern as a genotyping irregularity and, in that situation, the doubt about the tri-allele locus frequency calculation can reduce the analysis strength. In the TPOX human STR locus, tri-allelic genotypes have been reported with a widely varied frequency among human populations. We investigate whether there is a single extra allele (the third allele) in the TPOX tri-allelic pattern, what it is, and where it is, aiming to understand its genomic anatomy and to propose the knowledge of this TPOX extra allele from genetic profile, thus preserving the two standard TPOX alleles in forensic analyses. We looked for TPOX tri-allelic subjects in 75,113 Brazilian families. Considering only the parental generation (mother+father) we had 150,226 unrelated subjects evaluated. From this total, we found 88 unrelated subjects with tri-allelic pattern in the TPOX locus (0.06%; 88/150,226). Seventy three of these 88 subjects (73/88; 83%) had the Clayton's original Type 2 tri-allelic pattern (three peaks of even intensity). The remaining 17% (15/88) show a new Type 2 derived category with heterozygote peak imbalance (one double dose peak plus one regular sized peak). In this paper we present detailed data from 66 trios (mother+father+child) with true biological relationships. In 39 of these families (39/66; 59%) the extra TPOX allele was transmitted either from the mother or from the father to the child. Evidences indicated the allele 10 as the extra TPOX allele, and it is on the X chromosome. The present data, which support the previous Lane hypothesis, improve the knowledge about tri-allelic pattern of TPOX CODIS' locus allowing the use of TPOX profile in forensic analyses even when with tri-allelic pattern. This evaluation is now available for different forensic applications. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Increased prevalence of mutant null alleles that cause hereditary fructose intolerance in the American population.

PubMed

Coffee, Erin M; Yerkes, Laura; Ewen, Elizabeth P; Zee, Tiffany; Tolan, Dean R

2010-02-01

Mutations in the aldolase B gene (ALDOB) impairing enzyme activity toward fructose-1-phosphate cleavage cause hereditary fructose intolerance (HFI). Diagnosis of the disease is possible by identifying known mutant ALDOB alleles in suspected patients; however, the frequencies of mutant alleles can differ by population. Here, 153 American HFI patients with 268 independent alleles were analyzed to identify the prevalence of seven known HFI-causing alleles (A149P, A174D, N334K, Delta4E4, R59Op, A337V, and L256P) in this population. Allele-specific oligonucleotide hybridization analysis was performed on polymerase chain reaction (PCR)-amplified genomic DNA from these patients. In the American population, the missense mutations A149P and A174D are the two most common alleles, with frequencies of 44% and 9%, respectively. In addition, the nonsense mutations Delta4E4 and R59Op are the next most common alleles, with each having a frequency of 4%. Together, the frequencies of all seven alleles make up 65% of HFI-causing alleles in this population. Worldwide, these same alleles make up 82% of HFI-causing mutations. This difference indicates that screening for common HFI alleles is more difficult in the American population. Nevertheless, a genetic screen for diagnosing HFI in America can be improved by including all seven alleles studied here. Lastly, identification of HFI patients presenting with classic symptoms and who have homozygous null genotypes indicates that aldolase B is not required for proper development or metabolic maintenance.

[China expert consensus on the management of dyslipidemia in postmenopausal patients with early-stage breast cancer].

PubMed

2017-01-23

Estrogen has an impact on the type of lipoproteins and the blood lipid levels, thus protecting the cardiovascular system. Postmenopausal breast cancer patients suffer a significant decrease in estrogen levels due to both physiological changes and the use of drugs, and thus have a higher risk of atherosclerotic cardiovascular diseases. Therefore, strict lipid management is required for postmenopausal breast cancer patients receiving endocrine therapy. However, no guidelines have been developed in terms of lipid management and intervention for postmenopausal breast cancer patients. The Chinese expert group of multidisciplinary management of dyslipidemia in breast cancer patients with endocrine therapy, after deep investigation into the management of dyslipidemia in postmenopausal patients with early-stage breast cancer, has developed the China Expert Consensus on Dyslipidemia Management in Postmenopausal Patients with Early-stage Breast Cancer. The Consensus clearly defines the goals and measures of interventions for dyslipidemia, hoping to effectively reduce the risk of atherosclerotic cardiovascular disease in postmenopausal breast cancer patients and further improve the long-term survival of the patients.

A Review of the Efficacy, Safety, and Clinical Implications of Naturally Derived Dietary Supplements for Dyslipidemia.

PubMed

Thaipitakwong, Thanchanit; Aramwit, Pornanong

2017-02-01

Dyslipidemia is recognized as a major cause of cardiovascular disease. A number of evidence-based guidelines recommend conventional synthetic drugs as standard therapy for dyslipidemia in clinical practice. However, antihyperlipidemic drugs have some serious side effects. Naturally derived dietary supplements are becoming attractive as an alternative strategy because of their high efficacy and safety, as supported by numerous data. Moreover, they could be considered an initial treatment for dyslipidemia. The aims of this literature review were to demonstrate the efficacy, safety, and clinical implications of dietary supplements for treating dyslipidemia. We reviewed the literature, including data from in vitro, in vivo, and human studies, and clinical guideline recommendations. We classified dietary supplements by their proposed mechanisms of action on lipid metabolism and also collected daily dosage recommendations, interactions with concurrent drugs and/or foods, dosage forms, and examples of commercially available products. Various types of naturally derived dietary supplements exhibit lipid-improving properties. Efficacy and safety are acceptable; however, their use in clinical practice will require further well-designed investigations and the support of scientific data.

Different Criteria for the Definition of Insulin Resistance and Its Relation with Dyslipidemia in Overweight and Obese Children and Adolescents

PubMed Central

de Mello, Elza Daniel

2018-01-01

Purpose to compare cut off points corrected for age and gender (COOP) with fixed cut off points (FCOP) for fasting plasma insulin and Homeostatic model assessment-insulin resistance (HOMA-IR) for the diagnosis of IR in obese children and adolescents and their correlation with dyslipidemia. Methods A multicenter, cross-sectional study including 383 subjects aged 7 to 18 years, evaluating fasting blood glucose, plasma insulin, and lipid profile. Subjects with high insulin levels and/or HOMA-IR were considered as having IR, based on two defining criteria: FCOP or CCOP. The frequency of metabolic abnormalities, the presence of IR, and the presence of dyslipidemia in relation to FCOP or CCOP were analyzed using Fisher and Mann-Whitney exact tests. Results Using HOMA-IR, IR was diagnosed in 155 (40.5%) and 215 (56.1%) patients and, using fasting insulin, 150 (39.2%) and 221 (57.7%), respectively applying FCOP and CCOP. The use of CCOP resulted in lower insulin and HOMA-IR values than FCOP. Dyslipidemia was not related to FCOP or CCOP. Blood glucose remained within normal limits in all patients with IR. There was no difference in the frequency of IR identified by plasma insulin or HOMA-IR, both for FCOP and CCOP. Conclusion The CCOP of plasma insulin or of HOMA-IR detected more cases of IR as compared to the FCOP, but were not associated with the frequency of dyslipidemia. As blood glucose has almost no fluctuation in this age group, even in the presence of IR, fasting plasma insulin detected the same cases of IR that would be detected by HOMA-IR. PMID:29383306

[Prevalence of dyslipidemia and its influential factors in 2 028 students from primary and middle schools in Changsha].

PubMed

Li, Yamei; Luo, Jiayou; Ma, Jun; Zou, Zhiyong; Liu, Xiaoqun; Li, Huixia

2017-06-28

To determine the prevalence of dyslipidemia in students from the primary and middle schools and the influential factors, and to provide evidence for the prevention and control of dyslipidemia and relevant chronic diseases in primary and middle schools. 
 Methods: A total of 2 028 students aged 7 to 17 from the primary and middle schools in Changsha were selected by stratified random cluster sampling. The contents of the study included questionnaire survey, physical measurement and blood tests for fasting blood triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels. Non-high-density lipoprotein cholesterol (non-HDL-C) level was calculated by TC level minus HDL-C level. Chi-square test and non-conditional logistic regression model were used to analyze the factors that contributed to dyslipidemia.
 Results: The dyslipidemia rate was 18.6%, and the abnormal rates of TG, TC, LDL-C, non-HDL-C and HDL-C were 6.8%, 5.6%, 2.3%, 4.2% and 8.6%, respectively. By chi-square test, the dyslipidemia rate in students with different ages, home locations, BMI groups, central obesity, time on watching TV or playing computer per day, and daily sleep time was statistically significant. Non-conditional logistic regression analysis showed that home location for the city (OR=1.332), overweight (OR=1.548), obesity (OR=2.201), central obesity (OR=1.695), watching TV or playing computer for more than 2 hours per day (OR=1.357), daily sleep time longer than 11 hours (OR=2.518) were the risk factors for dyslipidemia in students from the primary and middle schools. 
 Conclusion: Nearly 1/5 primary and middle school students show dyslipidemia, which is associated with obesity and other bad behaviors.

Different effects of bariatric surgical procedures on dyslipidemia: a registry-based analysis.

PubMed

Spivak, Hadar; Sakran, Nasser; Dicker, Dror; Rubin, Moshe; Raz, Itamar; Shohat, Tamy; Blumenfeld, Orit

2017-07-01

The scale and variables linked to bariatric surgery's effect on dyslipidemia have not been conclusive. To compare the effect of Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and adjustable gastric banding (LAGB) on dyslipidemia SETTING: National bariatric surgery registry. Plasma lipids and associated variables were compared at baseline and 1 year (12±4 mo) after surgery for registry patients with dyslipidemia enrolled from June 2013 to August 2014. The greatest mean total-cholesterol (TC) reduction was observed post-RYGB, 226.7±26.4 to 181.3±30.9 mg/dL (19.9%, n = 208), followed by post-SG, 227.9±24.4 to 206.7±34.2 mg/dL (8.9%, n = 1515; P<.001). Normal TC levels of below 200 mg/dL were achieved by 76% post-RYGB patients compared with 43.5% post-SG patients (odds ratio [OR] = 6.24, 95% confidence interval [CI]: 3.69-10.53) and 25.6% post-LABG patients (OR = 9.66, 95% CI: 4.11-22.67; P<.01). Although equivalent patterns were observed for low-density-lipoprotein cholesterol (LDL), the levels of high-density-lipoprotein cholesterol (HDL) were most improved post-SG, reaching normal levels in 58.1% of SG male patients versus 39.5% of RYGB male patients (OR = 1.56, 95% CI: 1.04-2.35), (P = .02). The lowering of triglyceride levels by approximately 75% was comparable after SG and RYGB procedures. The type of surgery was the strongest independent predictor for all lipid level improvements or remissions. Male sex was an independent predictor for LDL normalization only (OR = 1.88, 95% CI: 1.24-2.85). Excess weight loss offered no meaningful prediction for lipid improvement (OR = 1.01-1.03). Particular types of bariatric surgeries had different effects on dyslipidemia, independent of weight loss. Overall, the RYGB achieved the biggest reduction in plasma lipids (TC and LDL), although SG did affect HDL. Our results could aid in the decision-making process regarding the most appropriate procedure for patients with dyslipidemia. Copyright © 2017 American

High serum apolipoprotein E determines hypertriglyceridemic dyslipidemias, coronary disease and apoA-I dysfunctionality.

PubMed

Onat, Altan; Can, Günay; Ornek, Ender; Ayhan, Erkan; Erginel-Ünaltuna, Nihan; Murat, Sani N

2013-01-01

The relevance of serum apolipoprotein E (apoE) levels to two hypertriglyceridemic dyslipidemias has not been clarified. We explored, in a cross-sectional (and short-term prospective) evaluation, the independent relationship of serum apoE to the atherogenic dyslipidemia, hypertriglyceridemia with elevated apoB (HtgB) and to apoA-I dysfunctionality, previously shown in Turkish adults to be independent of apoE genotype. Serum apoE concentrations were measured by immunonephelometry in 1,127 middle-aged adults. In multivariable regression analysis, apoE concentrations showed log-linear associations with apoB and apoA-I levels, waist circumference, independent of C-reactive protein (CRP), homeostatic model assessment (HOMA) index and other confounders. The likelihood of atherogenic dyslipidemia and of HtgB roughly tripled per 1-SD increment in apoE concentrations, additively to apoE genotype, HOMA, apoA-I, CRP concentrations and waist circumference; yet apoA-I, protective against atherogenic dyslipidemia, appeared to promote HtgB, a finding consistent with apoA-I dysfunctionality in this setting. Each 1-SD increment in the apoE level was moreover, associated in both genders with MetS (at OR 1.5), after adjustment for sex, age, apoB, apoA-I and CRP, or for apoE genotypes. Circulating apoE predicted in both genders age-adjusted prevalent and incident coronary heart disease (CHD), independent of apoE genotype and CRP (OR 1.32 [95 % CI 1.11; 1.58]). To conclude, in a general population prone to MetS, elevated apoE concentrations are strongly linked to HtgB and atherogenic dyslipidemia, irrespective of apoE genotype, are associated with MetS and CHD. Excess apoE reflects pro-inflammatory state and likely autoimmune activation.

Prevalence of dyslipidemia and its association with other coronary artery disease risk factors among urban population in Southeast of Iran: results of the Kerman coronary artery disease risk factors study (KERCADRS).

PubMed

Najafipour, Hamid; Shokoohi, Mostafa; Yousefzadeh, Gholamreza; Sarvar Azimzadeh, Behzad; Moshtaghi Kashanian, Gholamreza; Bagheri, Mohamad Mehdi; Mirzazadeh, Ali

2016-01-01

Despite the importance of identifying and screening dyslipidemia to prevent coronary artery diseases CAD(Coronary Artery Disease), little information is available on dyslipidemia in our large area. So the present study aimed to assess the management status of lipid abnormalities and its association with other CAD risk factors in an urban population of southeast of Iran. This cross-sectional study was a part of the Kerman coronary artery disease risk factor study KERCADRS (Kerman coronary artery disease risk study) as a population-based, epidemiological research among 5900 individuals aged 15 to 75 years who were residents of Kerman city, the largest city in Southeast of Iran. Lipid profile was assessed using enzymatic laboratory methods. In total, 5558 persons from 5899 participants were assessed in whom 45.1 % were male and 54.9 % female. Overall 20.9 % had borderline level of cholesterol (200-239 mg/dl) and 8.7 % suffered from hypercholesterolemia (≥240 mg/dl). The prevalence of undiagnosed dyslipidemia (UDL) was 16.8 % and of diagnosed dyslipidemia (DDL) was 13.2 % that both UDL and DDL were more prevalent in women. Also, UDL was more revealed in third and fourth age decades. Advanced age, anxiety, obesity (BMI ≥30 Kg/m 2 ), and family history of dyslipidemia predicted dyslipidemia in study population. The overall prevalence of UDL was higher than of DDL, and was significantly influenced by advanced age, anxiety, obesity, and family history of dyslipidemia. The data showed that our health care management system should improve its strategies to reduce the burden of this important CAD risk factor.

Detection of 549 new HLA alleles in potential stem cell donors from the United States, Poland and Germany.

PubMed

Hernández-Frederick, C J; Cereb, N; Giani, A S; Ruppel, J; Maraszek, A; Pingel, J; Sauter, J; Schmidt, A H; Yang, S Y

2016-01-01

We characterized 549 new human leukocyte antigen (HLA) class I and class II alleles found in newly registered stem cell donors as a result of high-throughput HLA typing. New alleles include 101 HLA-A, 132 HLA-B, 105 HLA-C, 2 HLA-DRB1, 89 HLA-DQB1 and 120 HLA-DPB1 alleles. Mainly, new alleles comprised single nucleotide variations when compared with homologous sequences. We identified nonsynonymous nucleotide mutations in 70.7% of all new alleles, synonymous variations in 26.4% and nonsense substitutions in 2.9% (null alleles). Some new alleles (55, 10.0%) were found multiple times, HLA-DPB1 alleles being the most frequent among these. Furthermore, as several new alleles were identified in individuals from ethnic minority groups, the relevance of recruiting donors belonging to such groups and the importance of ethnicity data collection in donor centers and registries is highlighted. © 2015 The Authors. HLA published by John Wiley & Sons Ltd.

DLA-DRB1, DQA1, and DQB1 alleles and haplotypes in North American Gray Wolves.

PubMed

Kennedy, Lorna J; Angles, John M; Barnes, Annette; Carmichael, Lindsey E; Radford, Alan D; Ollier, William E R; Happ, George M

2007-01-01

The canine major histocompatibility complex contains highly polymorphic genes, many of which are critical in regulating immune response. Since domestic dogs evolved from Gray Wolves (Canis lupus), common DLA class II alleles should exist. Sequencing was used to characterize 175 Gray Wolves for DLA class II alleles, and data from 1856 dogs, covering 85 different breeds of mostly European origin, were available for comparison. Within wolves, 28 new alleles were identified, all occurring in at least 2 individuals. Three DLA-DRB1, 8 DLA-DQA1, and 6 DLA-DQB1 alleles also identified in dogs were present. Twenty-eight haplotypes were identified, of which 2 three-locus haplotypes, and many DLA-DQA1/DQB1 haplotypes, are also found in dogs. The wolves studied had relatively few dog DLA alleles and may therefore represent a remnant population descended from Asian wolves. The single European wolf included carried a haplotype found in both these North American wolves and in many dog breeds. Furthermore, one wolf DQB1 allele has been found in Shih Tzu, a breed of Asian origin. These data suggest that the wolf ancestors of Asian and European dogs may have had different gene pools, currently reflected in the DLA alleles present in dog breeds.

HLA-B27 allele frequency in Sri Lankan patients with spondyloarthritides.

PubMed

Kidnapillai, S; Sirisena, N D; Dissanayake, V H

2016-06-01

This preliminary study aims to describe the HLA-B27 allele frequency in Sri Lankan patients with spondyloarthritides (SA). An anonymised database of 373 Sri Lankan patients with SA referred for HLA-B27 testing was retrospectively analysed. Eighty five (22.8%) patients were positive for the HLA-B27 allele. A male preponderance was observed among the positives. The HLA-B27 allele frequency in this sample of patients with SA was relatively low compared to published studies in other populations. Further research is needed to identify the predominant subtypes of the allele to determine which subtypes are the most prevalent in a larger sample of Sri Lankan patients with SA, and to define their association with the specific types of SA.

S-genotype identification based on allele-specific PCR in Japanese pear

PubMed Central

Nashima, Kenji; Terakami, Shingo; Nishio, Sogo; Kunihisa, Miyuki; Nishitani, Chikako; Saito, Toshihiro; Yamamoto, Toshiya

2015-01-01

Gametophytic self-incompatibility in Japanese pear (Pyrus pyrifolia Nakai) is controlled by the single, multi-allelic S-locus. Information about the S-genotypes is important for breeding and the selection of pollen donors for fruit production. Rapid and reliable S-genotype identification system is necessary for efficient breeding of new cultivars in Japanese pear. We designed S allele-specific PCR primer pairs for ten previously reported S-RNase alleles (S1–S9 and Sk) as simple and reliable method. Specific nucleotide sequences were chosen to design the primers to amplify fragments of only the corresponding S alleles. The developed primer pairs were evaluated by using homozygous S-genotypes (S1/S1–S9/S9 and S4sm/S4sm) and 14 major Japanese pear cultivars, and found that S allele-specific primer pairs can identify S-genotypes effectively. The S allele-specific primer pairs developed in this study will be useful for efficient S-genotyping and for marker-assisted selection in Japanese pear breeding programs. PMID:26175617

Association of Fitness With Incident Dyslipidemias Over 25 Years in the Coronary Artery Risk Development in Young Adults Study.

PubMed

Sarzynski, Mark A; Schuna, John M; Carnethon, Mercedes R; Jacobs, David R; Lewis, Cora E; Quesenberry, Charles P; Sidney, Stephen; Schreiner, Pamela J; Sternfeld, Barbara

2015-11-01

Few studies have examined the longitudinal associations of fitness or changes in fitness on the risk of developing dyslipidemias. This study examined the associations of (1) baseline fitness with 25-year dyslipidemia incidence and (2) 20-year fitness change on dyslipidemia development in middle age in the Coronary Artery Risk Development in Young Adults Study (CARDIA). Multivariable Cox proportional hazards regression models were used to test the association of baseline fitness (1985-1986) with dyslipidemia incidence over 25 years (2010-2011) in CARDIA (N=4,898). Modified Poisson regression models were used to examine the association of 20-year change in fitness with dyslipidemia incidence between Years 20 and 25 (n=2,487). Data were analyzed in June 2014 and February 2015. In adjusted models, the risk of incident low high-density lipoprotein cholesterol (HDL-C); high triglycerides; and high low-density lipoprotein cholesterol (LDL-C) was significantly lower, by 9%, 16%, and 14%, respectively, for each 2.0-minute increase in baseline treadmill endurance. After additional adjustment for baseline trait level, the associations remained significant for incident high triglycerides and high LDL-C in the total population and for incident high triglycerides in both men and women. In race-stratified models, these associations appeared to be limited to whites. In adjusted models, change in fitness did not predict 5-year incidence of dyslipidemias, whereas baseline fitness significantly predicted 5-year incidence of high triglycerides. Our findings demonstrate the importance of cardiorespiratory fitness in young adulthood as a risk factor for developing dyslipidemias, particularly high triglycerides, during the transition to middle age. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Association of Fitness With Incident Dyslipidemias Over 25 Years in the Coronary Artery Risk Development in Young Adults Study

PubMed Central

Sarzynski, Mark A.; Schuna, John M.; Carnethon, Mercedes R.; Jacobs, David R.; Lewis, Cora E.; Quesenberry, Charles P.; Sidney, Stephen; Schreiner, Pamela J.; Sternfeld, Barbara

2015-01-01

Introduction Few studies have examined the longitudinal associations of fitness or changes in fitness on the risk of developing dyslipidemias. This study examined the associations of: (1) baseline fitness with 25-year dyslipidemia incidence; and (2) 20-year fitness change on dyslipidemia development in middle age in the Coronary Artery Risk Development in young Adults (CARDIA) study. Methods Multivariable Cox proportional hazards regression models were used to test the association of baseline fitness (1985–1986) with dyslipidemia incidence over 25 years (2010–2011) in CARDIA (N=4,898). Modified Poisson regression models were used to examine the association of 20-year change in fitness with dyslipidemia incidence between Years 20 and 25 (n=2,487). Data were analyzed in June 2014 and February 2015. Results In adjusted models, the risk of incident low high-density lipoprotein cholesterol (HDL-C), high triglycerides, and high low-density lipoprotein cholesterol (LDL-C) was significantly lower, by 9%, 16%, and 14%, respectively, for each 2.0-minute increase in baseline treadmill endurance. After additional adjustment for baseline trait level, the associations remained significant for incident high triglycerides and high LDL-C in the total population and for incident high triglycerides in both men and women. In race-stratified models, these associations appeared to be limited to whites. In adjusted models, change in fitness did not predict 5-year incidence of dyslipidemias, whereas baseline fitness significantly predicted 5-year incidence of high triglycerides. Conclusions Our findings demonstrate the importance of cardiorespiratory fitness in young adulthood as a risk factor for developing dyslipidemias, particularly high triglycerides, during the transition to middle age. PMID:26165197

Prevalence, patterns, and associations of dyslipidemia among Sri Lankan adults-Sri Lanka Diabetes and Cardiovascular Study in 2005-2006.

PubMed

Katulanda, Prasad; Dissanayake, Harsha Anuruddhika; De Silva, S D Neomal; Katulanda, Gaya Wijeweera; Liyanage, Isurujith Kongala; Constantine, Godwin Roger; Sheriff, Rezvi; Matthews, David R

Dyslipidemia is a major risk factor for cardiovascular disease. Prevalence patterns and determinants of dyslipidemia in Sri Lanka are unkown. We aimed to determine the prevalence and correlates of dyslipidemia among Sri Lankan adults. A nationally representative sample was recruited by multistage random cluster sampling in Sri Lanka Diabetes and Cardiovascular Study, a cross-sectional study. Data collected by an interviewer-administered questionnaire, physical examination, anthropometric measurements lipid analysis from take 12-hour fasting blood samples were used. Among 4451 participants 60.5% were women and mean age was 46 years. Mean (standard deviation) total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), triglycerides (TGs), and TC/HDLC levels were 206.7 mg/dL (±43.5), 46.8 mg/dL (±10.6), 135.5 mg/dL (±37.6), 121.7 mg/dL (±66.8), and 4.6 (±1.1), respectively. Women had higher mean TC, HDLC, LDLC, and TG values compared to men across all age groups. Mean TC, LDLC, and TGs increased with age in both genders; 77.4% of participants had some form of dyslipidemia. Low HDLC was the commonest type (49.6%) of dyslipidemia. Increasing age, female sex, living in urban sector, high body mass index, central obesity, diabetes, hypertension, insufficient physical activity, and smoking were associated with having some form of dyslipidemia. Three in four Sri Lankan adults have some form of dyslipidemia. Physical inactivity, obesity, hypertension, and diabetes are the leading modifiable risk factors. Copyright © 2018 National Lipid Association. All rights reserved.

Association between dyslipidemia and chronic kidney disease: a cross-sectional study in the middle-aged and elderly Chinese population.

PubMed

Liu, Dong-Wei; Wan, Jia; Liu, Zhang-Suo; Wang, Pei; Cheng, Gen-Yang; Shi, Xue-Zhong

2013-04-01

Dyslipidemia, a well-known risk factor for cardiovascular disease, is common in patients with kidney disease. Recent studies discerned that dyslipidemias play a critical role in renal damage progression in renal diseases, but the association between dyslipidemias and chronic kidney disease (CKD) in the general population remains unknown. Thus, we assessed whether the growing prevalence of dyslipidemia could increase the risk of CKD. A total of 4779 middle-aged and elderly participants participated in this study. Dyslipidemias were defined by the 2007 Guidelines in Chinese Adults. Incident CKD was defined as albuminuria and/or reduced estimated glomerular filtration rate (eGFR, < 60 ml×min(-1)×1.73 m(-2)). Regression analysis was used to evaluate the association between dyslipidemia and albuminuria/reduced eGFR. Participants with hypercholesterolemia exhibited a greater prevalence of albuminuria and reduced eGFR (10.0% vs. 6.1%, P = 0.001; 4.0% vs. 2.4%, P = 0.028, respectively). Both hypercholesterolemia and low high density lipoprotein cholesterol (HDL-C) were independently associated with albuminuria (odds ratio (OR) 1.49; 95% confidence interval (CI) 1.08 - 2.07 and OR 1.53; 95%CI 1.13 - 2.09, respectively). The multivariable adjusted OR of reduced eGFR in participants with hypercholesterolemia was 1.65 (95%CI 1.03 - 2.65). As the number of dyslipidemia components increased, so did the OR of CKD: 0.87 (95%CI 0.65 - 1.15), 1.29 (95%CI, 0.83 - 2.01), and 7.87 (95%CI, 3.75 - 16.50) for albuminuria, and 0.38 (95%CI 0.21 - 0.69), 1.92 (95%CI 1.14 - 3.25), and 5.85 (95%CI 2.36 - 14.51) for reduced eGFR, respectively. Our findings indicate that dyslipidemias increase the risk of CKD in the middle-aged and elderly Chinese population. Hypercholesterolemia plays an important role in reducing total eGFR. Both low HDL-C and hypercholesterolemia are associated with an increased risk for albuminuria.

Rohitukine inhibits in vitro adipogenesis arresting mitotic clonal expansion and improves dyslipidemia in vivo.

PubMed

Varshney, Salil; Shankar, Kripa; Beg, Muheeb; Balaramnavar, Vishal M; Mishra, Sunil Kumar; Jagdale, Pankaj; Srivastava, Shishir; Chhonker, Yashpal S; Lakshmi, Vijai; Chaudhari, Bhushan P; Bhatta, Rabi Shankar; Saxena, Anil Kumar; Gaikwad, Anil Nilkanth

2014-06-01

We developed a common feature pharmacophore model using known antiadipogenic compounds (CFPMA). We identified rohitukine, a reported chromone anticancer alkaloid as a potential hit through in silico mapping of the in-house natural product library on CFPMA. Studies were designed to assess the antiadipogenic potential of rohitukine. Rohitukine was isolated from Dysoxylum binacteriferum Hook. to ⬧95% purity. As predicted by CFPMA, rohitukine was indeed found to be an antiadipogenic molecule. Rohitukine inhibited lipid accumulation and adipogenic differentiation in a concentration- and exposure-time-dependent manner in 3T3-L1 and C3H10T1/2 cells. Rohitukine downregulated expression of PPARγ, CCAAT/enhancer binding protein α, adipocyte protein 2 (aP2), FAS, and glucose transporter 4. It also suppressed mRNA expression of LPL, sterol-regulatory element binding protein (SREBP) 1c, FAS, and aP2, the downstream targets of PPARγ. Rohitukine arrests cells in S phase during mitotic clonal expansion. Rohitukine was bioavailable, and 25.7% of orally administered compound reached systemic circulation. We evaluated the effect of rohitukine on dyslipidemia induced by high-fat diet in the hamster model. Rohitukine increased hepatic expression of liver X receptor α and decreased expression of SREBP-2 and associated targets. Rohitukine decreased hepatic and gonadal lipid accumulation and ameliorated dyslipidemia significantly. In summary, our strategy to identify a novel antiadipogenic molecule using CFPMA successfully resulted in identification of rohitukine, which confirmed antiadipogenic activity and also exhibited in vivo antidyslipidemic activity. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

Effect of the treatment with Euterpe oleracea Mart. oil in rats with Triton-induced dyslipidemia.

PubMed

E Souza, Belmira S Faria; Carvalho, Helison O; Ferreira, Irlon M; da Cunha, Edilson L; Barros, Albenise Santana; Taglialegna, Talisson; Carvalho, José C T

2017-06-01

Dyslipidemias are defined as changes in lipid metabolism that have abnormal concentrations of lipids or lipoproteins in the bloodstream. Chronic increase in triglyceride and low-density lipoprotein (LDL-c) levels are known as risk factors for the atherogenesis process as well as other cardiovascular diseases (CVDs). The magnitude of the problems caused by dyslipidemias impels research by new agents that act in the prevention and control. Thus, products from the Amazonian biodiversity, such as Euterpe oleracea oil (OFEO), rich in unsaturated fatty acids (UFAs), constitutes a study source for the treatment of alterations in lipid metabolism. The present study aims to investigate the effect of OFEO treatment in rats with Triton-induced dyslipidemia (Tyloxapol WR1339). The physicochemical and chromatographic results confirmed the chemical composition of OFEO with a predominance of UFAs (67.83%), with Oleic acid being the majority (54.32%). At Triton-induced dyslipidemia, the animals treated with OFEO and Simvastatin showed a significant reduction in total cholesterol levels, with values ​​of 121.7±29.5 (p<0.01) and 96.6±17.6mg/dL (p<0.001), respectively. OFEO also significantly reduced LDL-c levels (p<0.01) and triglycerides (p<0.001). OFEO and Simvastatin improved the lipid profile by significantly increasing (p<0.05) the high-density lipoprotein (HDL) values. Therefore, it is concluded that the OFEO treatment used in the conditions of this study had a beneficial effect on dyslipidemia, acting as antihypercholesterolemic and antihypertriglyceridemic, thus possibly contributing as a preventive agent for CVDs. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Osteosarcopenic obesity and its relationship with dyslipidemia in women from different ethnic groups of China.

PubMed

Mo, Dan; Hsieh, Peishan; Yu, Hongrong; Zhou, Lining; Gong, Jichun; Xu, Lin; Liu, Peng; Chen, Gang; Chen, Zhao; Deng, Qiongying

2018-06-09

To explore the prevalence and ethnic differences of osteosarcopenic obesity (OSO) and dyslipidemia and their relationship among Maonan, Mulam, Hmong, and Yao minorities in China. A total of 2315 Maonan, Mulam, Hmong, and Yao women aged 20-95 from Guangxi were included in this study. Questionnaire survey was carried out and their blood lipids were tested. Body compositions were measured by bioelectrical impedance analysis, and T-score was assessed by ultrasonic examination, respectively. Our study showed ethnic-specific prevalence of OSO. In older women, the incidence rates of OSO in Mulam were 4.9, 12.6, and 11.5% in Maonan, Mulam, and Hmong ethnicity, respectively. In younger group, the incidence rates of OSO were 0.4, 0.4, and 0.6%, respectively. However, there is no prevalence of OSO in Yao women in two groups. The prevalence of dyslipidemia in younger women was 22.86, 29.89, 43.35, and 80.00% in group numbering one, two, and three, respectively. In older women, it was 29.13, 39.02, 41.37, and 52.38%, respectively. Based on logistic regression analysis, after controlling for covariates, dyslipidemia in younger group was positively associated with a higher number of adverse body composition, especially for OSO (OR = 12.53, 95%CI 1.34-116.99). Compared with normal women, OSO women in older group were also more likely to have dyslipidemia (OR = 6.75, 95%CI 3.19-14.31). OSO may be a risk factor for dyslipidemia in the ethnic groups. Thus, efforts to promote healthy aging should be focused on preventing obesity and maintaining bone health and muscle mass.

Allelic Analysis of Sheath Blight Resistance with Association Mapping in Rice

PubMed Central

Jia, Limeng; Yan, Wengui; Zhu, Chengsong; Agrama, Hesham A.; Jackson, Aaron; Yeater, Kathleen; Li, Xiaobai; Huang, Bihu; Hu, Biaolin; McClung, Anna; Wu, Dianxing

2012-01-01

Sheath blight (ShB) caused by the soil-borne pathogen Rhizoctonia solani is one of the most devastating diseases in rice world-wide. Global attention has focused on examining individual mapping populations for quantitative trait loci (QTLs) for ShB resistance, but to date no study has taken advantage of association mapping to examine hundreds of lines for potentially novel QTLs. Our objective was to identify ShB QTLs via association mapping in rice using 217 sub-core entries from the USDA rice core collection, which were phenotyped with a micro-chamber screening method and genotyped with 155 genome-wide markers. Structure analysis divided the mapping panel into five groups, and model comparison revealed that PCA5 with genomic control was the best model for association mapping of ShB. Ten marker loci on seven chromosomes were significantly associated with response to the ShB pathogen. Among multiple alleles in each identified loci, the allele contributing the greatest effect to ShB resistance was named the putative resistant allele. Among 217 entries, entry GSOR 310389 contained the most putative resistant alleles, eight out of ten. The number of putative resistant alleles presented in an entry was highly and significantly correlated with the decrease of ShB rating (r = −0.535) or the increase of ShB resistance. Majority of the resistant entries that contained a large number of the putative resistant alleles belonged to indica, which is consistent with a general observation that most ShB resistant accessions are of indica origin. These findings demonstrate the potential to improve breeding efficiency by using marker-assisted selection to pyramid putative resistant alleles from various loci in a cultivar for enhanced ShB resistance in rice. PMID:22427867

Molecular diversity of HLA-Cw alleles in the Maratha community of Mumbai, Maharashtra, western India.

PubMed

Shankarkumar, U; Ghosh, K; Mohanty, D

2005-08-01

Recent advances suggest a significant role for the HLA-C locus as a target of alloreactions after bone marrow transplantation. The biological importance of products of the HLA-C locus, both as transplant antigens and as ligands for natural killer (NK) cells, is well established. A total of 10 different serologically defined HLA-Cw antigen specificities (Cw1-Cw10) are encoded by the C locus; however, there are now 151 different alleles that can be identified by molecular methods. Serological definition of Cw alleles therefore includes 20-50% blanks, which cannot be detected by the available antisera. We used the molecular method of polymerase chain reaction (PCR)-based sequence-specific amplification and probe hybridization to define Cw alleles in 91 individuals from the Maratha community, and compared the data with data for 92 serologically typed Maratha individuals from India. We identified Cw*12, Cw*14, Cw*15, Cw*16 and Cw*18, along with the serologically identified Cw*01, Cw*02, Cw*03, Cw*04, Cw*06 and Cw*07 alleles. The HLA-Cw blank allele frequency in the Maratha was reduced from 0.5706 to 0.00. Furthermore, by using a molecular technique, it was possible to identify novel allele subtypes, such as Cw*0104, Cw*0203 and Cw*0707, and a high frequency of Cw* 1801 in the Maratha community compared with other Indian and world populations. Our results will have clinical implications in related and unrelated HLA-matched bone marrow transplantation in India.

Genetic linkage of hyperglycemia and dyslipidemia in an intercross between BALB/cJ and SM/J Apoe-deficient mouse strains.

PubMed

Wang, Qian; Grainger, Andrew T; Manichaikul, Ani; Farber, Emily; Onengut-Gumuscu, Suna; Shi, Weibin

2015-11-10

Individuals with dyslipidemia often develop type 2 diabetes, and diabetic patients often have dyslipidemia. It remains to be determined whether there are genetic connections between the 2 disorders. A female F2 cohort, generated from BALB/cJ (BALB) and SM/J (SM) Apoe-deficient (Apoe(-/-)) strains, was started on a Western diet at 6 weeks of age and maintained on the diet for 12 weeks. Fasting plasma glucose and lipid levels were measured before and after 12 weeks of Western diet. 144 genetic markers across the entire genome were used for quantitative trait locus (QTL) analysis. One significant QTL on chromosome 9, named Bglu17 [26.4 cM, logarithm of odds ratio (LOD): 5.4], and 3 suggestive QTLs were identified for fasting glucose levels. The suggestive QTL near the proximal end of chromosome 9 (2.4 cM, LOD: 3.12) was replicated at both time points and named Bglu16. Bglu17 coincided with a significant QTL for HDL (high-density lipoprotein) and a suggestive QTL for non-HDL cholesterol levels. Plasma glucose levels were inversely correlated with HDL but positively correlated with non-HDL cholesterol levels in F2 mice on either chow or Western diet. A significant correlation between fasting glucose and triglyceride levels was also observed on the Western diet. Haplotype analysis revealed that "lipid genes" Sik3, Apoa1, and Apoc3 were probable candidates for Bglu17. We have identified multiple QTLs for fasting glucose and lipid levels. The colocalization of QTLs for both phenotypes and the sharing of potential candidate genes demonstrate genetic connections between dyslipidemia and type 2 diabetes.

Dyslipidemia rather than Type 2 Diabetes Mellitus or Chronic Periodontitis Affects the Systemic Expression of Pro- and Anti-Inflammatory Genes.

PubMed

Nepomuceno, Rafael; Villela, Bárbara Scoralick; Corbi, Sâmia Cruz Tfaile; Bastos, Alliny De Souza; Dos Santos, Raquel Alves; Takahashi, Catarina Satie; Orrico, Silvana Regina Perez; Scarel-Caminaga, Raquel Mantuaneli

2017-01-01

A high percentage of type 2 diabetes mellitus (T2D) patients are also affected by dyslipidemia and chronic periodontitis (CP), but no studies have determined the gene expression in patients that are simultaneously affected by all three diseases. We investigated the systemic expression of immune-related genes in T2D, dyslipidemia, and CP patients. One hundred and fifty patients were separated into five groups containing 30 individuals each: (G1) poorly controlled T2D with dyslipidemia and CP; (G2) well-controlled T2D with dyslipidemia and CP; (G3) normoglycemic individuals with dyslipidemia and CP; (G4) healthy individuals with CP; (G5) systemic and periodontally healthy individuals. Blood analyses of lipid and glycemic profiles were carried out. The expression of genes, including IL10, JAK1, STAT3, SOCS3, IP10, ICAM1, IFNA, IFNG, STAT1, and IRF1, was investigated by RT-qPCR. Patients with dyslipidemia demonstrated statistically higher expression of the IL10 and IFNA genes, while IFNG, IP10, IRF1, JAK1, and STAT3 were lower in comparison with nondyslipidemic patients. Anti-inflammatory genes, such as IL10 , positively correlated with parameters of glucose, lipid, and periodontal profiles, while proinflammatory genes, such as IFNG , were negatively correlated with these parameters. We conclude that dyslipidemia appears to be the primary disease that is associated with gene expression of immune-related genes, while parameters of T2D and CP were correlated with the expression of these important immune genes.

Synergistic potential of Zingiber officinale and Curcuma longa to ameliorate diabetic-dyslipidemia.

PubMed

Hussain, Naveed; Hashmi, Abu-Saeed; Wasim, Muhammad; Akhtar, Tauqeer; Saeed, Shagufta; Ahmad, Toheed

2018-03-01

To find the cure of world's one of the leading morbid and mortal disorders; diabetes mellitus and its most prevalent complication, 'diabetic-dyslipidemia', is one of the leading health challenges of 21st century. The use of phytomedicine is a glimmer of hope in this scenario. Studies of current decade have shown that methanolic extracts of Zingiber officinale and Curcuma longa have highly effective therapeutic potentials against the aforesaid disorders, however, which of the extracts has more potential is still unclear. Furthermore, synergistic effect of the extracts has never been studied. Forty-eight Albino adult rats of either sex were randomly divided into eight groups. A-D groups were containing healthy rats while E-H groups were of induced diabetic-dyslipidemic rats. For forty-two days, rats of each group were given either distilled water or Zingiber officinale methanolic extract (ZOME) or Curcuma longa methanolic extract (CLME) or ZOME+CLME therapies at dose rate of 300mg/100 mL dist. H 2 O/kg body wt/day. FPG and lipid profiles were estimated before and after the trial, and were statistically analyzed by one-way ANOVA along with Post-hoc Tukey's multiple comparison tests. Although, ZOME and CLME significantly (P<0.05) lowered fasting plasma glucose (FPG) levels and controlled lipid profiles in diabetic-dyslipidemic rats; yet, synergistic therapy of both extracts (ZOME+CLME) most significantly (P<0.05) controlled all parameters of diabetic-dyslipidemia (78.00±1.06mg/dL FPG, 62.00±0.58mg/dL TG, 66.50±0.76mg/dL cholesterol, 32.00±0.36mg/dL HDL, 22.43±0.64 mg/dL LDL, and 12.40±0.12mg/dL VLDL). Our findings may be useful to formulate new medicines having multiple potentials to control diabetes mellitus, dyslipidemia, and diabetic-dyslipidemia.

Dyslipidemias and Cardiovascular Prevention: Tailoring Treatment According to Lipid Phenotype.

PubMed

Sanin, Veronika; Pfetsch, Vanessa; Koenig, Wolfgang

2017-07-01

This study aimed to present the current information on the genetic background of dyslipidemias and provide insights into the complex pathophysiological role of several plasma lipids/lipoproteins in the pathogenesis of atherosclerotic cardiovascular disease. Furthermore, we aim to summarize established therapies and describe the scientific rationale for the development of novel therapeutic strategies. Evidence from genetic studies suggests that besides lowering low-density lipoprotein cholesterol, pharmacological reduction of triglyceride-rich lipoproteins, or lipoprotein(a) will reduce risk for coronary heart disease. Dyslipidemia, in particular hypercholesterolemia, is a common clinical condition and represents an important determinant of atherosclerotic vascular disease. Treatment decisions are currently guided by the causative lipid phenotype and the presence of other risk factors suggesting a very high cardiovascular risk. Therefore, the identification of lipid disorders and the optimal combination of therapeutic strategies provide an outstanding opportunity for reducing the onset and burden of cardiovascular disease.

Diversity of HLA-B61 alleles and haplotypes in East Asians and Spanish Gypsies.

PubMed

Ogawa, A; Tokunaga, K; Lin, L; Kashiwase, K; Tanaka, H; Herrero, M J; Vilches, C; Park, M H; Jia, G J; Chimge, N O; Sideltseva, E W; Ishikawa, Y; Akaza, T; Tadokoro, K; Juji, T

1998-04-01

The distribution of HLA-B61 alleles and their association with HLA-C and DRB1 alleles were investigated in six East Asian populations (South Korean, Chinese Korean, Man (Manchu), Northern Han, Mongolian and Buryat) and Spanish Gypsies and compared to our previous report on the Japanese population. The alleles were identified using a group-specific polymerase chain reaction (PCR) and genomic DNA followed by hybridization with sequence-specific oligonucleotide probes (SSOP). Both HLA-B*4002 and B*4006 were commonly detected in the South Korean, Chinese Korean, Man, Northern Han and Japanese populations, while HLA-B*4002 was predominant in the Mongolian and Buryat populations. Strong associations of B*4002 with Cw*0304 and of B*4006 with Cw*0801 were commonly observed in these East Asian populations. In contrast, in Spanish Gypsies, only HLA-B*4006 was found and the allele exhibited a strong association with Cw*1502. HLA-B*4003 was also identified in the South Korean, Chinese Korean, Northern Han, Mongolian and Japanese populations at relatively low frequencies, and exhibited an association with Cw*0304. Moreover, the association of these B61 alleles with the DRB1 alleles revealed considerable diversity among the different populations. HLA-B*4004 and B*4009 were not observed in these populations. Consequently, the frequencies of the B61 alleles varied among the different East Asian populations, but the individual B61 alleles were carried by specific haplotypes often regardless of the ethnic differences.

Allelic variation contributes to bacterial host specificity

DOE PAGES

Yue, Min; Han, Xiangan; Masi, Leon De; ...

2015-10-30

Understanding the molecular parameters that regulate cross-species transmission and host adaptation of potential pathogens is crucial to control emerging infectious disease. Although microbial pathotype diversity is conventionally associated with gene gain or loss, the role of pathoadaptive nonsynonymous single-nucleotide polymorphisms (nsSNPs) has not been systematically evaluated. Here, our genome-wide analysis of core genes within Salmonella enterica serovar Typhimurium genomes reveals a high degree of allelic variation in surface-exposed molecules, including adhesins that promote host colonization. Subsequent multinomial logistic regression, MultiPhen and Random Forest analyses of known/suspected adhesins from 580 independent Typhimurium isolates identifies distinct host-specific nsSNP signatures. Moreover, population andmore » functional analyses of host-associated nsSNPs for FimH, the type 1 fimbrial adhesin, highlights the role of key allelic residues in host-specific adherence in vitro. In conclusion, together, our data provide the first concrete evidence that functional differences between allelic variants of bacterial proteins likely contribute to pathoadaption to diverse hosts.« less

[Prevalence of dyslipidemia and normal blood lipids level in Uygur population in Kashgar area of Xinjiang Uygur Autonomous Region].

PubMed

Zhang, Z B; Xue, Z X; Wu, X J; Wang, T M; Li, Y H; Song, X L; Chao, X F; Wang, G; Nazibam, Nurmamat; Ayxamgul, Bawudun; Gulbahar, Elyas; Zhou, Z Y; Sun, B S; Wang, Y Z; Wang, M

2017-06-10

Objective: To understand the prevalence of dyslipidemia and normal blood lipids level in Uygur diabetes patients in Kashgar prefecture in southern area of Xinjiang. Methods: A total of 5 078 local residents aged ≥18 years (42.56 % were men) selected through cluster random sampling in Kashgar were surveyed by means of questionnaire survey, physical examination and laboratory test, and 521 diabetes patients were screened. Results: The overall prevalence of dyslipidemia in diabetes patients was 59.50 % (310/521) with adjusted rate as 49.39 % . Age ≥65 years, overweight, obesity and abdominal obesity increased the risk for dyslipidemia by 0.771 times (95 % CI : 1.015-3.088), 1.132 times (95 % CI : 1.290-3.523), 1.688 times (95 % CI : 1.573-4.592) and 0.801 times (95 % CI : 1.028-3.155) respectively. Compared with males, female was a protective factor for dyslipidemia ( OR =0.507, 95 %CI : 0.334-0.769). The overall normal rate of blood lipids level including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) for type 2 diabetes patients was 11.13 % . Female, higher BMI and abdominal obesity were the factors influencing the overall normal blood lipids level. The normal rate of LDL-C level decreased with increase of age, BMI and waist circumferences (trend test χ (2)=18.049, P <0.001; trend test χ (2)=10.582, P =0.001; χ (2)=19.081, P <0.001), but increased with educational level (trend test χ (2)=9.764, P =0.002). Conclusion: The prevalence of dyslipidemia in Uygur diabetes patients in Kashgar was high, however, the overall normal rate of blood lipid level was relatively low. Obesity was the most important risk factor for dyslipidemia in this area. More attention should be paid to dyslipidemia prevention in women.

Prevalence of dyslipidemia according to the nutritional status in a representative sample of São Paulo.

PubMed

Garcez, Marcela Riccioppo; Pereira, Jaqueline Lopes; Fontanelli, Mariane de Mello; Marchioni, Dirce Maria Lobo; Fisberg, Regina Mara

2014-12-01

Overweight is one of the major public health problems in Brazil; it is associated with dyslipidemia, which is an important risk factor for cardiovascular diseases. To evaluate the lipid profile of residents of the municipality of São Paulo, state of São Paulo, according to the nutritional status. Data from the population-based cross-sectional study ISA-Capital 2008 on a sample of residents of São Paulo were used. Participants were categorized into groups according to body mass index and age range. The levels of total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and non-HDL cholesterol were measured. The association between lipid profile, nutricional status, and waist circumference was investigated. The data were processed using the survey mode of the Stata 11.0 software. The prevalence of any type of dyslipidemia in the population was 59.74%, with low HDL-cholesterol dyslipidemia being the most common type. Not overweight individuals had higher mean levels of HDL-cholesterol and lower levels of LDL-cholesterol, total cholesterol, triglycerides, and non-HDL cholesterol when compared with the overweight group. The rate of inadequacy of these variables was higher in the overweight individuals, regardless of the age group, to the exception of LDL-cholesterol in the adults and elderly. A higher prevalence of isolated hypertriglyceridemia was observed in individuals with higher waist circumference among the adults and the total population. The results indicate an association between dyslipidemia and overweight in the population of the city of São Paulo. The most prevalent dyslipidemia in this population was low HDL-cholesterol.

[Dyslipidemias : Diagnostics and management].

PubMed

Sinning, D; Landmesser, U

2017-09-01

For disorders of lipid metabolism the risk-adapted adjustment of low-density lipoprotein (LDL) cholesterol remains the primary treatment target, as a causal role in minimizing the progression of ACVD has been shown. Because of their efficacy in reducing cardiovascular morbidity and mortality, statins are recommended as first-line pharmacological treatment in dyslipidemias. Additionally, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition have been shown to significantly reduce cardiovascular events in high-risk patients. Life style changes can improve the plasma lipid profile, particularly in the setting of hypertriglyceridemia. Evaluation of high-density lipoprotein (HDL) cholesterol and lipoprotein(a) provides further information when assessing the individual cardiovascular risk, but direct evidence that pharmacologically targeting HDL cholesterol or Lp(a) results in a reduction of cardiovascular events has not yet been shown.

Obesity and dyslipidemia in patients with psoriasis treated at a dermatologic clinic in Manaus.

PubMed

Santos, Mônica; Fonseca, Hannah Monteiro; Jalkh, Alex Panizza; Gomes, Gabriela Piraice; Cavalcante, Andrea de Souza

2013-01-01

Psoriasis is a chronic inflammatory disease of multifactorial etiology, with participation of genetic, autoimmune and environmental factors. Recent studies have demonstrated the role of inflammatory cells and mediators in the pathogenesis of psoriasis, which is now defined as a systemic and autoimmune inflammatory disease that may be associated with other diseases of inflammatory nature. To evaluate the occurrence of obesity and dyslipidemia in patients with psoriasis treated at a dermatology clinic in Manaus. We performed a prospective descriptive study to assess the prevalence of obesity and dyslipidemia in patients with psoriasis. Besides the recommended dermatological care, a physical examination was performed to measure weight, height and waist circumference. We included 72 patients, 44 (61.1%) female and 28 (38.9%) male, with a mean age of 51.0 years ± 15.9 years. As for body mass index (BMI), 16 (22.2%) were overweight and 20 (27.8%) were obese. In the analysis of waist circumference in relation to gender, we found that 79.5% of women surveyed had central obesity, a percentage statistically higher than that observed among men (42.9%) at the 5% level of significance (p = 0.001). Regarding the diagnosis of dyslipidemia, 29 (65.9%) females and 22 (78.6%) males showed alterations in lipid profile. The occurrence of dyslipidemia and obesity in patients with psoriasis can affect life quality and expectancy, increasing the risk of systemic and metabolic diseases, which makes periodic investigation of these comorbidities in patients with psoriasis mandatory.

[Allelic variation at high-molecular-weight glutenin subunit loci in Aegilops biuncialis Vis].

PubMed

Kozub, N A; Sozinov, I A; Ksinias, I N; Sozinov, A A

2011-09-01

Alleles at the high-molecular-weight glutenin subunit loci Glu-U1 and Glu-M(b)1 were analyzed in the tetraploid species Aegilops biuncialis (UUM(b)M(b)). The material for the investigation included the collection of 39 accessions of Ae. biuncialis from Ukraine (the Crimea), one Hellenic accession, one accession of unknown origin, F2 seeds from different crosses, as well as samples from natural populations from the Crimea. Ae. umbellulata and Ae. comosa accessions were used to allocate components of the HMW glutenin subunit patterns of Ae. biuncialis to U or M(b) genomes. Eight alleles were identified at the Glu-U1 locus and ten alleles were revealed at the Glu-M(b) 1 locus. Among alleles at the Glu-M(b) 1 locus ofAe. biuncialis there were two alleles controlling the y-type subunit only and one allele encoding the x-subunit only.

Influence of dyslipidemia in control of arterial hypertension among type-2 diabetics in the western region of the Republic of Macedonia.

PubMed

Jani, Ylber; Kamberi, Amet; Ferati, Fatmir; Rexhepi, Atila; Pocesta, Bekim; Orovcanec, Nikola; Lala, Dali; Polisi, Gafur; Iseni, Mair; Mirto, Arben; Zeqiri, Agim

2014-01-01

To determine the influence of dyslipidemia in control of blood pressure in patients with type 2 Diabetes. To test the hypothesis that, blood pressure and lipid levels are not sufficiently controlled in patients with type 2 Diabetes, in the western region of the Republic of Macedonia. Abnormalities of lipid and lipoprotein levels in the serum (dyslipidemia) are recognized as major modifiable cardiovascular disease risk factors and have been identified as independent risk factors for essential hypertension, giving rise to the term dyslipidemic hypertension. While patient-related data from primary care that demonstrate an under-treatment of blood pressure and dyslipidemia in type 2 Diabetics are vastly available in clinical practice, results from population-based studies are scarce. The study was conducted on outpatients in Primary Health Care Clinics in 8 cities on the western region of the Republic of Macedonia. Prospectively the tests were performed on 600 (45.6% women and 54.4% men) participants with a mean age of 62 ± 5.8. Study participants were selected among primary care patients, who were actively on therapy for diabetes mellitus and hypertension during the period of March 2013 - March 2014. Patients' demographic characteristics, clinical laboratory and drug usage data were obtained. The patients were classified according to the BP control, into 2 groups. A total of 600 patients, of which 45.6% female and 54.3% male, completed the survey and had data for a 1-year medical record review. It was observed that a high percentage, 65.3% of patients, did not have controlled blood pressure despite the ongoing medical treatment, according to evidence and current guidelines in a cohort of hypertensive diabetics. (Chi-square: 19.85, p<0.001). Among participants with controled BP, untreated or insufficiently treated dyslipidemia was recorded in 23% of them, whereas among participants with uncontrolled BP, untreated or insufficiently treated dyslipidemia was recorded in

Influence of dyslipidemia in control of arterial hypertension among type-2 diabetics in the western region of the Republic of Macedonia

PubMed Central

Jani, Ylber; Kamberi, Amet; Ferati, Fatmir; Rexhepi, Atila; Pocesta, Bekim; Orovcanec, Nikola; Lala, Dali; Polisi, Gafur; Iseni, Mair; Mirto, Arben; Zeqiri, Agim

2014-01-01

Objective: To determine the influence of dyslipidemia in control of blood pressure in patients with type 2 Diabetes. To test the hypothesis that, blood pressure and lipid levels are not sufficiently controlled in patients with type 2 Diabetes, in the western region of the Republic of Macedonia. Background: Abnormalities of lipid and lipoprotein levels in the serum (dyslipidemia) are recognized as major modifiable cardiovascular disease risk factors and have been identified as independent risk factors for essential hypertension, giving rise to the term dyslipidemic hypertension. While patient-related data from primary care that demonstrate an under-treatment of blood pressure and dyslipidemia in type 2 Diabetics are vastly available in clinical practice, results from population-based studies are scarce. Material and methods: The study was conducted on outpatients in Primary Health Care Clinics in 8 cities on the western region of the Republic of Macedonia. Prospectively the tests were performed on 600 (45.6% women and 54.4% men) participants with a mean age of 62 ± 5.8. Study participants were selected among primary care patients, who were actively on therapy for diabetes mellitus and hypertension during the period of March 2013 - March 2014. Patients’ demographic characteristics, clinical laboratory and drug usage data were obtained. The patients were classified according to the BP control, into 2 groups. Results: A total of 600 patients, of which 45.6% female and 54.3% male, completed the survey and had data for a 1-year medical record review. It was observed that a high percentage, 65.3% of patients, did not have controlled blood pressure despite the ongoing medical treatment, according to evidence and current guidelines in a cohort of hypertensive diabetics. (Chi-square: 19.85, p<0.001). Among participants with controled BP, untreated or insufficiently treated dyslipidemia was recorded in 23% of them, whereas among participants with uncontrolled BP, untreated

Polycystic Ovary Syndrome and Increased Soluble Tumor Necrosis Factor Like Weak Inducer of Apoptosis Levels Are Independent Predictors of Dyslipidemia in Youth.

PubMed

Erkenekli, Kudret; Oztas, Efser; Kuscu, Elif; Keskin, Uğur; Kurt, Yasemin Gulcan; Tas, Ahmet; Yilmaz, Nafiye

2017-01-01

Dyslipidemia is common in women with polycystic ovary syndrome (PCOS) irrespective of age. Our aim was to investigate soluble tumor necrosis factor like weak inducer of apoptosis (sTWEAK), a cardiovascular risk marker in PCOS, and to determine if it is associated with dyslipidemia in youth. A prospective-observational study was carried out including 35 PCOS patients and 35 healthy controls. Serum sTWEAK levels were measured using commercially available kits. Multiple logistic regression analysis was then performed to verify the statistically significant differences in the possible predictors of dyslipidemia. Serum sTWEAK levels and the percentage of women with dyslipidemia were significantly higher in the PCOS group (p = 0.024 and p < 0.001, respectively). Participants were further divided into 2 subgroups based on the presence of dyslipidemia. The percentage of women with PCOS was significantly higher in the dyslipidemic group when compared with controls; 70.7 vs. 20.7%, respectively (p < 0.001). Multiple logistic regression analysis revealed that both the presence of PCOS (OR 7.924, 95% CI 2.117-29.657, p = 0.002) and increased levels of sTWEAK (>693 pg/ml; OR 3.810, 95% CI 1.075-13.501, p = 0.038) were independently associated with dyslipidemia. Increased levels of both sTWEAK and PCOS were found to be independently associated with dyslipidemia in youth. © 2016 S. Karger AG, Basel.

Influence of polygenic risk scores on lipid levels and dyslipidemia in a psychiatric population receiving weight gain-inducing psychotropic drugs.

PubMed

Delacrétaz, Aurélie; Lagares Santos, Patricia; Saigi Morgui, Nuria; Vandenberghe, Frederik; Glatard, Anaïs; Gholam-Rezaee, Mehdi; von Gunten, Armin; Conus, Philippe; Eap, Chin B

2017-12-01

Dyslipidemia represents a major health issue in psychiatry. We determined whether weighted polygenic risk scores (wPRSs) combining multiple single-nucleotide polymorphisms (SNPs) associated with lipid levels in the general population are associated with lipid levels [high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), and triglycerides] and/or dyslipidemia in patients receiving weight gain-inducing psychotropic drugs. We also determined whether genetics improve the predictive power of dyslipidemia. The influence of wPRS on lipid levels was firstly assessed in a discovery psychiatric sample (n=332) and was then tested for replication in an independent psychiatric sample (n=140). The contribution of genetic markers to predict dyslipidemia was evaluated in the combined psychiatric sample. wPRSs were significantly associated with the four lipid traits in the discovery (P≤0.02) and in the replication sample (P≤0.03). Patients whose wPRS was higher than the median wPRS had significantly higher LDL, TC, and triglyceride levels (0.20, 0.32 and 0.26 mmol/l, respectively; P≤0.004) and significantly lower HDL levels (0.13 mmol/l; P<0.0001) compared with others. Adding wPRS to clinical data significantly improved dyslipidemia prediction of HDL (P=0.03) and a trend for improvement was observed for the prediction of TC dyslipidemia (P=0.08). Population-based wPRSs have thus significant effects on lipid levels in the psychiatric population. As genetics improved the predictive power of dyslipidemia development, only 24 patients need to be genotyped to prevent the development of one case of HDL hypocholesterolemia. If confirmed by further prospective investigations, the present results could be used for individualizing psychotropic treatment.

Effects of aqueous extracts of dried calyx of sour tea (Hibiscus sabdariffa L.) on polygenic dyslipidemia: A randomized clinical trial.

PubMed

Hajifaraji, Majid; Matlabi, Mohammad; Ahmadzadeh-Sani, Farihe; Mehrabi, Yadollah; Rezaee, Mohammad Salem; Hajimehdipour, Homa; Hasanzadeh, Abbas; Roghani, Katayoun

2018-01-01

Dyslipidemia has been considered as a major risk factor for coronary heart disease. Alternative medicine has a significant role in treatment of dyslipidemia. There are controversial findings regarding the effects of sour tea on dyslipidemia. The aim of this study was to evaluate the impact of aqueous extract of dried calyx of sour tea on polygenic dyslipidemia. This clinical trial was done on 43 adults (30-60 years old) with polygenic dyslipidemia that were randomly assigned to the intervention and control groups. The control group was trained in lifestyle modifications at baseline. The intervention group was trained for lifestyle modifications at baseline and received two cups of sour tea daily, and both groups were followed up for 12 weeks. Lipid profile was evaluated at baseline, and six and 12 weeks following the intervention. In addition, dietary and physical activity assessed at baseline for twelve weeks. Mean concentration of total cholesterol, HDL-C and LDL-C significantly decreased by up to 9.46%, 8.33%, and 9.80%, respectively, after 12 weeks in the intervention group in comparison to their baseline values. However, LDL-C/HDL-C ratio significantly increased by up to 3.15%, following 12 weeks in the control group in comparison to their baseline values. This study showed no difference in lipid profiles between the two groups, except for HDL-C concentrations. sour tea may have significant positive effects on lipid profile of polygenic dyslipidemia subjects and these effect might be attributed to its anthocyanins and inflation factor content. Therefore, sour tea intake with recommended dietary patterns and physical activity can be useful in regulation of lipid profile in patients with polygenic dyslipidemia.

Using the Textpresso Site-Specific Recombinases Web server to identify Cre expressing mouse strains and floxed alleles.

PubMed

Condie, Brian G; Urbanski, William M

2014-01-01

Effective tools for searching the biomedical literature are essential for identifying reagents or mouse strains as well as for effective experimental design and informed interpretation of experimental results. We have built the Textpresso Site Specific Recombinases (Textpresso SSR) Web server to enable researchers who use mice to perform in-depth searches of a rapidly growing and complex part of the mouse literature. Our Textpresso Web server provides an interface for searching the full text of most of the peer-reviewed publications that report the characterization or use of mouse strains that express Cre or Flp recombinase. The database also contains most of the publications that describe the characterization or analysis of strains carrying conditional alleles or transgenes that can be inactivated or activated by site-specific recombinases such as Cre or Flp. Textpresso SSR complements the existing online databases that catalog Cre and Flp expression patterns by providing a unique online interface for the in-depth text mining of the site specific recombinase literature.

Does the Prevalence of Dyslipidemias Differ between Newfoundland and the Rest of Canada? Findings from the Electronic Medical Records of the Canadian Primary Care Sentinel Surveillance Network

PubMed Central

Asghari, Shabnam; Aref-Eshghi, Erfan; Hurley, Oliver; Godwin, Marshall; Duke, Pauline; Williamson, Tyler; Mahdavian, Masoud

2015-01-01

Introduction: Newfoundland and Labrador (NL) has the highest prevalence of cardiovascular disease (CVD) in Canada. Dyslipidemia is a risk factor for CVD. This study compares the prevalence of dyslipidemia in the NL population with the rest of Canada. Methods: A cross-sectional study, using data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN), was undertaken. The study population included adults, excluding pregnant women, aged 20 years and older. Canadian guidelines were used for classifying dyslipidemia. Univariate and multivariate analyses were conducted to compare the lipid levels and prevalence of dyslipidemia between NL and the rest of Canada. Results: About 128,825 individuals (NL: 7,772; rest of Canada: 121,053) were identified with a mean age of 59 years (55% females). Mean levels of total cholesterol (4.96 vs. 4.93, p = 0.03), low-density lipoprotein (LDL) (3.00 vs. 2.90 mmol/L, p < 0.0001), triglyceride (1.47 vs. 1.41 mmol/L, p < 0.0001), and high-density lipoprotein (HDL) (1.29 vs. 1.39 mmol/L, p < 0.0001) were significantly different in NL compared to the rest of Canada. Dyslipidemias of LDL (29 vs. 25% p < 0.0001), HDL (38 vs. 27%, p < 0.0001), and triglyceride (29 vs. 26%, p < 0.0001) were significantly more common in NL. After adjustment for confounding variables, NL inhabitants were more likely to have dyslipidemia of total cholesterol (OR: 1.16, 95% CI: 1.10–1.23, p < 0.0001), HDL (OR: 1.52, 95% CI: 1.44–1.60, p < 0.0001), LDL (OR: 1.38, 95% CI: 1.30–1.46, p < 0.0001), and ratio (OR: 1.53, 95% CI: 1.42–1.60, p < 0.0001). Conclusion: The NL population has a significantly higher rate of dyslipidemia compared to the rest of Canada, and the mean levels of all lipid components are worse in NL. Distinct cultural and genetic features of the NL population may explain this, accounting for a higher rate of CVD in NL. PMID:26664873

Tissue-specific patterns of allelically-skewed DNA methylation

PubMed Central

Marzi, Sarah J.; Meaburn, Emma L.; Dempster, Emma L.; Lunnon, Katie; Paya-Cano, Jose L.; Smith, Rebecca G.; Volta, Manuela; Troakes, Claire; Schalkwyk, Leonard C.; Mill, Jonathan

2016-01-01

ABSTRACT While DNA methylation is usually thought to be symmetrical across both alleles, there are some notable exceptions. Genomic imprinting and X chromosome inactivation are two well-studied sources of allele-specific methylation (ASM), but recent research has indicated a more complex pattern in which genotypic variation can be associated with allelically-skewed DNA methylation in cis. Given the known heterogeneity of DNA methylation across tissues and cell types we explored inter- and intra-individual variation in ASM across several regions of the human brain and whole blood from multiple individuals. Consistent with previous studies, we find widespread ASM with > 4% of the ∼220,000 loci interrogated showing evidence of allelically-skewed DNA methylation. We identify ASM flanking known imprinted regions, and show that ASM sites are enriched in DNase I hypersensitivity sites and often located in an extended genomic context of intermediate DNA methylation. We also detect examples of genotype-driven ASM, some of which are tissue-specific. These findings contribute to our understanding of the nature of differential DNA methylation across tissues and have important implications for genetic studies of complex disease. As a resource to the community, ASM patterns across each of the tissues studied are available in a searchable online database: http://epigenetics.essex.ac.uk/ASMBrainBlood. PMID:26786711

Weight change after 20 years of age and the incidence of dyslipidemia: a cohort study of Japanese male workers.

PubMed

Sogabe, N; Sawada, S S; Lee, I-M; Kawakami, R; Ishikawa-Takata, K; Nakata, Y; Mitomi, M; Noguchi, J; Tsukamoto, K; Miyachi, M; Blair, S N

2016-06-01

While heavier weight is known to increase the incidence of dyslipidemia, limited data are available on the relationship between weight gain and its development. A total of 2647 males were categorized into the following four groups according to the difference between their self-reported weight at 20 years of age and their measured weight in 1994-95: a loss of ≥5% (decrease), loss of <5% or gain of <5% (no change), gain of ≥5 to <15% (increase) and gain of ≥15% (sizable increase). They were followed up until their 2002-03 health examination. Using the 'no change' group as reference, the multivariable-adjusted odds ratio (adjusted for age, body mass index at 20 years of age, physical activity, smoking and alcohol intake) and 95% confidence interval (95% CI) for the incidence of dyslipidemia were determined using logistic regression models. A total of 1342 participants developed dyslipidemia during the follow-up period. The 'increase' and 'sizable increase' groups had odds ratios for the incidence of dyslipidemia of 1.97 (95% CI, 1.59-2.45) and 2.68 (2.15-3.34), respectively, demonstrating that there was a significant dose-response association between weight gain since 20 years of age and the incidence of dyslipidemia (P < 0.001 for trend). These results suggest that dyslipidemia could be prevented by avoiding weight gain in adulthood. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Risk reductions for cardiovascular disease with pravastatin treatment by dyslipidemia phenotype: a post hoc analysis of the MEGA Study.

PubMed

Nishiwaki, Masato; Ikewaki, Katsunori; Ayaori, Makoto; Mizuno, Kyoichi; Ohashi, Yasuo; Ohsuzu, Fumitaka; Ishikawa, Toshitsugu; Nakamura, Haruo

2013-03-01

The beneficial effect of statins for cardiovascular disease (CVD) prevention has been well established. However, the effectiveness among different phenotypes of dyslipidemia has not been confirmed. We evaluated the effect of pravastatin on the incidence of CVD in relation to the phenotype of dyslipidemia. The MEGA Study evaluated the effect of low-dose pravastatin on primary prevention of CVD in 7832 Japanese patients, who were randomized to diet alone or diet plus pravastatin and followed for more than 5 years. These patients were classified into phenotype IIa (n=5589) and IIb (n=2041) based on the electrophoretic pattern for this post hoc analysis. In the diet group there was no significant difference in the incidence of coronary heart disease (CHD), stroke, CVD, and total mortality between the two phenotypes. Phenotype IIb patients, compared to phenotype IIa, had lower levels of high-density lipoprotein cholesterol (HDL-C) and a significantly higher incidence of CVD in relation to a low HDL-C level (<47.5mg/dL; p=0.02). Furthermore, pravastatin decreased the relative risk for each major endpoint in both type IIa and type IIb dyslipidemia. Significant risk reductions were observed for CHD by 38% (p=0.04) and CVD by 31% (p=0.02) in type IIa dyslipidemia but not in phenotype IIb. Pravastatin therapy provided significant risk reductions for CHD and CVD in patients with phenotype IIa dyslipidemia, but not in those with phenotype IIb dyslipidemia. Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Clinical Perspectives of Genetic Analyses on Dyslipidemia and Coronary Artery Disease

PubMed Central

Kawashiri, Masa-aki; Yamagishi, Masakazu

2017-01-01

We have learned that low-density lipoprotein (LDL) cholesterol is the cause of atherosclerosis from various aspects, including a single case with familial hypercholesterolemia, other cases with different types of Mendelian dyslipidemias, large-scale randomized controlled trials using LDL cholesterol lowering therapies, and Mendelian randomization studies using common as well as rare variants associated with LDL cholesterol levels. There is no doubt that determinations of genotypes in lipid-associated genes have contributed not only to the genetic diagnosis for Mendelian dyslipidemias but also to the discoveries of novel therapeutic targets. Furthermore, recent studies have shown that such genetic information could provide useful clues for the risk prediction as well as risk stratification in general and in particular population. We provide the current understanding of genetic analyses relating to plasma lipids and coronary artery disease. PMID:28250266

Global distribution of malaria-resistant MHC-HLA alleles: the number and frequencies of alleles and malaria risk.

PubMed

Garamszegi, László Zsolt

2014-09-03

The major histocompatibility complex (MHC) is the most polymorphic genetic region in vertebrates, but the origin of such genetic diversity remains unresolved. Several studies have demonstrated at the within-population level that individuals harbouring particular alleles can be less or more susceptible to malaria, but these do not allow strong generalization. Here worldwide data on the frequencies of several hundred MHC alleles of the human leucocyte antigen (HLA) system in relation to malaria risk at the between-population level were analysed in a phylogenetic framework, and results for different alleles were quantitatively summarized in a meta-analysis. There was an overall positive relationship between malaria pressure and the frequency of several HLA alleles indicating that allele frequencies increase in countries with strong malaria pressure. Nevertheless, considerable heterogeneity was observed across alleles, and some alleles showed a remarkable negative relationship with malaria risk. When heterogeneities were partitioned into different organization groups of the MHC, the strongest positive relationships were detected for alleles of the HLA-A and HLA-B loci, but there were also differences between MHC supertypes that constitute functionally distinct nucleotide sequences. Finally, the number of MHC alleles that are maintained within countries was also related to malaria risk. Therefore, malaria represents a key selection pressure for the human MHC and has left clear evolutionary footprints on both the frequencies and the number of alleles observed in different countries.

Dyslipidemia links obesity to early cerebral neurochemical alterations

PubMed Central

Haley, Andreana P.; Gonzales, Mitzi M.; Tarumi, Takashi; Tanaka, Hirofumi

2013-01-01

Objective To examine the role of hypertension, hyperglycemia and dyslipidemia in potentially accounting for obesity-related brain vulnerability in the form of altered cerebral neurochemistry. Design and Methods Sixty-four adults, ages 40 to 60 years, underwent a health screen and proton magnetic resonance spectroscopy (1H MRS) of occipitoparietal grey matter to measure N-acetyl aspartate (NAA), choline (Cho), myo-inositol (mI) and glutamate (Glu) relative to creatine (Cr). The causal steps approach and non-parametric bootstrapping were utilized to assess if fasting glucose, mean arterial pressure or peripheral lipid/lipoprotein levels mediate the relationship between body mass index (BMI) and cerebral neurochemistry. Results Higher BMI was significantly related to higher mI/Cr, independent of age and sex. BMI was also significantly related to two of the proposed mediators, triglyceride and HDL-cholesterol, which were also independently related to increased mI/Cr. Finally, the relationship between BMI and mI/Cr, was significantly attenuated after inclusion of triglyceride and HDL-cholesterol into the model, one at a time, indicating statistical mediation. Conclusions Higher triglyceride and lower HDL levels statistically account for the association between BMI and myo-inositol, pointing towards a potentially critical role for dyslipidemia in the development of cerebral neurochemical alterations in obesity. PMID:23512296

Dyslipidemia links obesity to early cerebral neurochemical alterations.

PubMed

Haley, Andreana P; Gonzales, Mitzi M; Tarumi, Takashi; Tanaka, Hirofumi

2013-10-01

To examine the role of hypertension, hyperglycemia, and dyslipidemia in potentially accounting for obesity-related brain vulnerability in the form of altered cerebral neurochemistry. Sixty-four adults, ages 40-60 years, underwent a health screen and proton magnetic resonance spectroscopy ((1) H MRS) of occipitoparietal gray matter to measure N-acetyl aspartate (NAA), choline (Cho), myo-inositol (mI), and glutamate (Glu) relative to creatine (Cr). The causal steps approach and nonparametric bootstrapping were utilized to assess if fasting glucose, mean arterial pressure or peripheral lipid/lipoprotein levels mediate the relationship between body mass index (BMI) and cerebral neurochemistry. Higher BMI was significantly related to higher mI/Cr, independent of age and sex. BMI was also significantly related to two of the proposed mediators, triglyceride, and HDL-cholesterol, which were also independently related to increased mI/Cr. Finally, the relationship between BMI and mI/Cr was significantly attenuated after inclusion of triglyceride and HDL-cholesterol into the model, one at a time, indicating statistical mediation. Higher triglyceride and lower HDL levels statistically account for the association between BMI and myo-inositol, pointing toward a potentially critical role for dyslipidemia in the development of cerebral neurochemical alterations in obesity. Copyright © 2013 The Obesity Society.

Prevalence of dyslipidemia in adults with cystic fibrosis.

PubMed

Rhodes, Bronwen; Nash, Edward F; Tullis, Elizabeth; Pencharz, Paul B; Brotherwood, Michelle; Dupuis, Annie; Stephenson, Anne

2010-01-01

A high fat calorie diet is advocated for patients with cystic fibrosis (CF) however the lipid profiles of individuals with CF, including those with CF-related diabetes (CFRD), are not well studied. We conducted a retrospective review of adult CF patients attending St Michael's Hospital between January 2005 and December 2007. 334 patients (77% pancreatic insufficient (PI)) were included in the study. Mean HDL cholesterol was significantly lower in males (p<0.0001) with 44% of males having HDL cholesterol <38.7mg/dL(1mmol/L). Pancreatic sufficient patients were more likely than PI subjects to have total cholesterol >201mg/dL(5.2mmol/L) (p<0.01). 5% of subjects had triglyceride concentrations >195mg/dL(2.2mmol/L). Diabetes was diagnosed in 23% of subjects. Lipid profiles were similar between diabetics and non-diabetics. Total cholesterol and triglycerides both increased with increasing age and increasing BMI (p<0.01). Dyslipidemia occurs in CF patients however no differences in lipid profiles were seen between those with diabetes and those without. Fasting lipids should be monitored in CF patients, particularly those with PS, older age, and high BMI. As survival in CF increases, the prevalence of dyslipidemia may increase resulting in clinically important complications.

Dyslipidemia Screening of 9- to 11-Year-Olds at Well-Child Visits by Utah Pediatricians.

PubMed

Stipelman, Carole; Young, Paul C; Hemond, Joni; Brown, Laura L; Mihalopoulos, Nicole L

2017-12-01

In 2011, an expert National Institutes of Health panel published the "Integrated Guidelines for CV Health and Risk Reduction in Children and Adolescents," which recommended screening all children aged 9 to 11 years for dyslipidemia. It is unknown if this guideline is being followed. We surveyed members of the Utah chapter of the American Academy of Pediatrics to determine whether they performed universal lipid screening at well-child visits (WCV) on their patients at 9,10, or 11 years and how comfortable they were with evaluating and/or managing children with dyslipidemia. Of the 118 respondents who practiced primary care, only 18 (15%) screened all children at WCV; 86 (73%) tested "some," most commonly children who were obese or had a positive family history. 18% were unfamiliar with the guidelines; 28% were familiar with the guidelines but felt they were "inappropriate;" 98 (84%) of the respondents said they were "very or somewhat comfortable" evaluating children with dyslipidemia.

Apolipoprotein A-I and B levels, dyslipidemia and metabolic syndrome in south-west Chinese women with PCOS.

PubMed

Zhang, Jinxia; Fan, Ping; Liu, Hongwei; Bai, Huai; Wang, Ying; Zhang, Feng

2012-08-01

What are the relationships between apolipoprotein (apo) A-I and apoB concentrations, the apoB/apoA-I ratio and the prevalences of dyslipidemia and metabolic syndrome (MS) in south-west Chinese women with polycystic ovary syndrome (PCOS). There is a relatively high incidence of dyslipidemia and MS in south-west Chinese women with PCOS, especially in patients without hyperandrogenism. Patients with dyslipidemia are more obese, and have a more adverse glucose and lipid metabolic profile and higher apoB levels and apoB/apoA-I ratio. The increased apoB levels and apoB/A1 ratio and the MS are strongly associated with PCOS, suggesting that there is an increased risk of cardiovascular diseases in these patients. Dyslipidemia and MS have been widely studied in women with PCOS, but to date no data from south-west Chinese subjects have been available. The apoB/apoA-I ratio has been reported to be strongly associated with MS and insulin resistance (IR) and to be a reliable parameter that reflects lipid disturbances and the potential to develop atherosclerosis, but its relationship with PCOS is unclear. DESIGN This case-control study included 406 patients with PCOS and 342 control women between 17 and 40 years of age from a population in south-west China during 2006-2011. The diagnosis of PCOS was based on the revised 2003 Rotterdam criteria. The control group, consisting of women with infertility due to a Fallopian obstruction or the husband's infertility, women undergoing a pre-pregnancy check and healthy volunteers, was recruited from the same hospital during the same period. All women were not taking any medication known to affect carbohydrate or lipid or hormone metabolism for at least 3 months prior to the study, and were studied during the follicular phase of their menstrual cycle. MS was assessed by the National Cholesterol Education Program-Adult treatment Panel (NCEP-ATP) III criteria modified for Asian populations. Dyslipidemia was defined by one or more of the

Obesity and dyslipidemia in patients with psoriasis treated at a dermatologic clinic in Manaus*

PubMed Central

Santos, Mônica; Fonseca, Hannah Monteiro; Jalkh, Alex Panizza; Gomes, Gabriela Piraice; Cavalcante, Andrea de Souza

2013-01-01

BACKGROUND Psoriasis is a chronic inflammatory disease of multifactorial etiology, with participation of genetic, autoimmune and environmental factors. Recent studies have demonstrated the role of inflammatory cells and mediators in the pathogenesis of psoriasis, which is now defined as a systemic and autoimmune inflammatory disease that may be associated with other diseases of inflammatory nature. OBJECTIVES To evaluate the occurrence of obesity and dyslipidemia in patients with psoriasis treated at a dermatology clinic in Manaus. METHODS We performed a prospective descriptive study to assess the prevalence of obesity and dyslipidemia in patients with psoriasis. Besides the recommended dermatological care, a physical examination was performed to measure weight, height and waist circumference. RESULTS We included 72 patients, 44 (61.1%) female and 28 (38.9%) male, with a mean age of 51.0 years ± 15.9 years. As for body mass index (BMI), 16 (22.2%) were overweight and 20 (27.8%) were obese. In the analysis of waist circumference in relation to gender, we found that 79.5% of women surveyed had central obesity, a percentage statistically higher than that observed among men (42.9%) at the 5% level of significance (p = 0.001). Regarding the diagnosis of dyslipidemia, 29 (65.9%) females and 22 (78.6%) males showed alterations in lipid profile. CONCLUSIONS The occurrence of dyslipidemia and obesity in patients with psoriasis can affect life quality and expectancy, increasing the risk of systemic and metabolic diseases, which makes periodic investigation of these comorbidities in patients with psoriasis mandatory. PMID:24474099

Prehispanic Functional Foods and Nutraceuticals in the Treatment of Dyslipidemia Associated to Cardiovascular Disease: a Mini-Review.

PubMed

Ríos-Hoyo, Alejandro; Romo-Araiza, Alejandra; Meneses-Mayo, Marcos; Guttiérrez-Salmeán, Gabriela

2017-01-27

Dyslipidemia is an important modifi able risk factor for cardiovascular and metabolic diseases, which are responsible for a large number of mortality and disability cases around the globe. Different strategies have been used within the treatment of dyslipidemia, including lifestyle modifi cations, pharmacologic therapy, as well as functional foods and nutraceuticals. Functional foods have been used worldwide since ancient times, particularly, the prehispanic civilizations utilized several as medicinal foods. In the current pandemic of dyslipidemia as well as the nutritional transition, particularly in Latin America, the use of native functional foods represents an attractive target for the treatment and/ or prevention of these conditions. In this mini-review, evidence regarding different functional foods such as cacao, amaranth, chia, nopal, spirulina, as well as their nutraceutical compounds, including fl avonoids, omega-3 PUFAs, fi ber, prebiotics, lovastatin, c-phycocyanin, among others, and their mechanism of action are presented and discussed. Although such foods certainly are considered as attractive potential agents to target dyslipidemia thus decrease the associated cardiometabolic risk, we conclude that for most of the presented functional foods there is currently not enough evidence to support its recommendation and every-day use.

Prediction of Adult Dyslipidemia Using Genetic and Childhood Clinical Risk Factors: The Cardiovascular Risk in Young Finns Study.

PubMed

Nuotio, Joel; Pitkänen, Niina; Magnussen, Costan G; Buscot, Marie-Jeanne; Venäläinen, Mikko S; Elo, Laura L; Jokinen, Eero; Laitinen, Tomi; Taittonen, Leena; Hutri-Kähönen, Nina; Lyytikäinen, Leo-Pekka; Lehtimäki, Terho; Viikari, Jorma S; Juonala, Markus; Raitakari, Olli T

2017-06-01

Dyslipidemia is a major modifiable risk factor for cardiovascular disease. We examined whether the addition of novel single-nucleotide polymorphisms for blood lipid levels enhances the prediction of adult dyslipidemia in comparison to childhood lipid measures. Two thousand four hundred and twenty-two participants of the Cardiovascular Risk in Young Finns Study who had participated in 2 surveys held during childhood (in 1980 when aged 3-18 years and in 1986) and at least once in a follow-up study in adulthood (2001, 2007, and 2011) were included. We examined whether inclusion of a lipid-specific weighted genetic risk score based on 58 single-nucleotide polymorphisms for low-density lipoprotein cholesterol, 71 single-nucleotide polymorphisms for high-density lipoprotein cholesterol, and 40 single-nucleotide polymorphisms for triglycerides improved the prediction of adult dyslipidemia compared with clinical childhood risk factors. Adjusting for age, sex, body mass index, physical activity, and smoking in childhood, childhood lipid levels, and weighted genetic risk scores were associated with an increased risk of adult dyslipidemia for all lipids. Risk assessment based on 2 childhood lipid measures and the lipid-specific weighted genetic risk scores improved the accuracy of predicting adult dyslipidemia compared with the approach using only childhood lipid measures for low-density lipoprotein cholesterol (area under the receiver-operating characteristic curve 0.806 versus 0.811; P =0.01) and triglycerides (area under the receiver-operating characteristic curve 0.740 versus area under the receiver-operating characteristic curve 0.758; P <0.01). The overall net reclassification improvement and integrated discrimination improvement were significant for all outcomes. The inclusion of weighted genetic risk scores to lipid-screening programs in childhood could modestly improve the identification of those at highest risk of dyslipidemia in adulthood. © 2017 American Heart

The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in patients with dyslipidemia.

PubMed

Fruchart, Jean-Charles; Sacks, Frank; Hermans, Michel P; Assmann, Gerd; Brown, W Virgil; Ceska, Richard; Chapman, M John; Dodson, Paul M; Fioretto, Paola; Ginsberg, Henry N; Kadowaki, Takashi; Lablanche, Jean-Marc; Marx, Nikolaus; Plutzky, Jorge; Reiner, Zeljko; Rosenson, Robert S; Staels, Bart; Stock, Jane K; Sy, Rody; Wanner, Christoph; Zambon, Alberto; Zimmet, Paul

2008-11-17

Despite achieving targets for low-density lipoprotein (LDL) cholesterol, blood pressure, and glycemia in accordance with current standards of care, patients with dyslipidemia remain at high residual risk of vascular events. Atherogenic dyslipidemia, characterized by elevated triglycerides and low levels of high-density lipoprotein (HDL) cholesterol, often with elevated apolipoprotein B and non-HDL cholesterol, is common in patients with established cardiovascular disease (CVD), type 2 diabetes mellitus, or metabolic syndrome and contributes to both macrovascular and microvascular residual risk. However, atherogenic dyslipidemia is largely underdiagnosed and undertreated in clinical practice. The Residual Risk Reduction Initiative (R3i) was established to address this highly relevant clinical issue. The aims of this position paper are (1) to highlight evidence that atherogenic dyslipidemia is associated with residual macrovascular and microvascular risk in patients at high risk for CVD, despite current standards of care for dyslipidemia and diabetes; and (2) to recommend therapeutic intervention for reducing this residual vascular risk supported by evidence and expert consensus. Lifestyle modification with nutrition and exercise is an important, effective, and underutilized first step in reducing residual vascular risk. Therapeutic intervention aimed at achievement of all lipid targets is also often required. Combination lipid-modifying therapy, with the addition of niacin, a fibrate, or omega-3 fatty acids to statin therapy, increases the probability of achieving all lipid goals. Outcomes studies are in progress to evaluate whether these combination treatment strategies translate to a clinical benefit greater than that achieved with statins alone. The R3i highlights the need to address with lifestyle and/or pharmacotherapy the high level of residual risk of CVD events and microvascular complications among patients with dyslipidemia receiving therapy for high levels

Fructose, insulin resistance, and metabolic dyslipidemia

PubMed Central

Basciano, Heather; Federico, Lisa; Adeli, Khosrow

2005-01-01

Obesity and type 2 diabetes are occurring at epidemic rates in the United States and many parts of the world. The "obesity epidemic" appears to have emerged largely from changes in our diet and reduced physical activity. An important but not well-appreciated dietary change has been the substantial increase in the amount of dietary fructose consumption from high intake of sucrose and high fructose corn syrup, a common sweetener used in the food industry. A high flux of fructose to the liver, the main organ capable of metabolizing this simple carbohydrate, perturbs glucose metabolism and glucose uptake pathways, and leads to a significantly enhanced rate of de novo lipogenesis and triglyceride (TG) synthesis, driven by the high flux of glycerol and acyl portions of TG molecules from fructose catabolism. These metabolic disturbances appear to underlie the induction of insulin resistance commonly observed with high fructose feeding in both humans and animal models. Fructose-induced insulin resistant states are commonly characterized by a profound metabolic dyslipidemia, which appears to result from hepatic and intestinal overproduction of atherogenic lipoprotein particles. Thus, emerging evidence from recent epidemiological and biochemical studies clearly suggests that the high dietary intake of fructose has rapidly become an important causative factor in the development of the metabolic syndrome. There is an urgent need for increased public awareness of the risks associated with high fructose consumption and greater efforts should be made to curb the supplementation of packaged foods with high fructose additives. The present review will discuss the trends in fructose consumption, the metabolic consequences of increased fructose intake, and the molecular mechanisms leading to fructose-induced lipogenesis, insulin resistance and metabolic dyslipidemia. PMID:15723702

Whole Exome Sequencing in Dominant Cataract Identifies a New Causative Factor, CRYBA2, and a Variety of Novel Alleles in Known Genes

PubMed Central

Reis, Linda M.; Tyler, Rebecca C.; Muheisen, Sanaa; Raggio, Victor; Salviati, Leonardo; Han, Dennis P.; Costakos, Deborah; Yonath, Hagith; Hall, Sarah; Power, Patricia; Semina, Elena V.

2013-01-01

Pediatric cataracts are observed in 1–15 per 10,000 births with 10–25% of cases attributed to genetic causes; autosomal dominant inheritance is the most commonly observed pattern. Since the specific cataract phenotype is not sufficient to predict which gene is mutated, whole exome sequencing (WES) was utilized to concurrently screen all known cataract genes and to examine novel candidate factors for a disease-causing mutation in probands from 23 pedigrees affected with familial dominant cataract. Review of WES data for 36 known cataract genes identified causative mutations in nine pedigrees (39%) in CRYAA, CRYBB1, CRYBB3, CRYGC (2), CRYGD, GJA8 (2), and MIP and an additional likely causative mutation in EYA1; the CRYBB3 mutation represents the first dominant allele in this gene and demonstrates incomplete penetrance. Examination of crystallin genes not yet linked to human disease identified a novel cataract gene, CRYBA2, a member of the βγ-crystallin superfamily. The p.(Val50Met) mutation in CRYBA2 cosegregated with disease phenotype in a four-generation pedigree with autosomal dominant congenital cataracts with incomplete penetrance. Expression studies detected cryba2 transcripts during early lens development in zebrafish, supporting its role in congenital disease. Our data highlight the extreme genetic heterogeneity of dominant cataract as the eleven causative/likely causative mutations affected nine different genes and the majority of mutant alleles were novel. Furthermore, these data suggest that less than half of dominant cataract can be explained by mutations in currently known genes. PMID:23508780

High-Intensity Interval Training as a Tool for Counteracting Dyslipidemia in Women.

PubMed

Alvarez, Cristian; Ramirez-Campillo, Rodrigo; Martinez-Salazar, Cristian; Castillo, Angélica; Gallardo, Francisco; Ciolac, Emmanuel Gomes

2018-05-01

Sedentary overweight or obese adult (age<60 years) women, allocated in type 2 diabetes mellitus (T2DM, n =13), dyslipidemia alone (DYS, n =12), dyslipidemia associated with hyperglycaemia (DYSHG, N=12), or healthy control (CON, n =10) groups, had their lipid, glucose, blood pressure, endurance performance, and anthropometry variables assessed before and after 16 weeks of a thrice-weekly high-intensity interval training (HIIT) program. Triglycerides reduced significantly ( P <0.05) in all groups, and high-density lipoprotein increased ( P <0.01) in T2DM, DYS and DYSHG; however, low-density lipoprotein reduced ( P <0.05) only in DYSHG, and total cholesterol reduced ( P <0.01) only in DYS and DYSHG. Fasting glucose reduced ( P <0.05) significantly in T2DM, DYS and DYSHG, but with higher decreases in T2DM and DYSHG. Blood pressure, endurance performance and body composition improved ( P <0.05) in all groups. The HIIT program was effective for restoring lipid profile of DYS and DYSHG, and fasting glucose of DYSHG to levels similar to those of CON, with a weekly time commitment 25% to 56% lower than the minimum recommended in current exercise guidelines. These findings suggest that HIIT may be a time-efficient intervention for counteracting dyslipidemia. © Georg Thieme Verlag KG Stuttgart · New York.

Effects of pitavastatin add-on therapy on chronic kidney disease with albuminuria and dyslipidemia.

PubMed

Ohsawa, Masato; Tamura, Kouichi; Wakui, Hiromichi; Kanaoka, Tomohiko; Azushima, Kengo; Uneda, Kazushi; Haku, Sona; Kobayashi, Ryu; Ohki, Kohji; Haruhara, Kotaro; Kinguchi, Sho; Toya, Yoshiyuki; Umemura, Satoshi

2015-12-09

In non-dialysis chronic kidney disease (CKD) patients with dyslipidemia, statin therapy is recommended to prevent cardiovascular complications. Dyslipidemia has been also shown to be an independent risk factor for the progression of CKD. However, it is still unclear whether statin therapy exerts an inhibitory effect on renal deterioration in CKD patients with dyslipidemia. The purpose of the present study was to examine possible therapeutic effects of statin add-on therapy on renal function as well as parameters of lipid and glucose metabolism, arterial stiffness and oxidative stress, in comparison to diet therapy, in CKD patients with dyslipidemia. This study was a randomized, open-label, and parallel-group trial consisted of a 12-months treatment period in non-dialysis CKD patients with alubuminuria and dyslipidemia. Twenty eight patients were randomly assigned either to receive diet counseling alone (diet therapy group) or diet counseling plus pitavastatin (diet-plus-statin therapy group), to achieve the LDL-cholesterol (LDL-C) target of <100 mg/dl. The statin treatment by pitavastatin was well tolerated in all of the patients without any significant adverse events and the average dose of pitavastatin was 1.0 ± 0.0 mg daily after treatment. After the 12-months treatment period, LDL-C was significantly lower in the diet-plus-statin therapy group compared with the diet therapy group (diet vs diet-plus-statin: LDL-C, 126 ± 5 vs 83 ± 4 mg/dL, P < 0.001). On the other hand, the diet-plus-statin therapy did not significantly reduce albuminuria or delay the decline in eGFR compared with the diet therapy, and there was no relationship between the change in LDL-C and the change in eGFR or albuminuria. However, diet therapy as well as diet-plus-statin therapy exerted similar lowering effects on the pentosidine levels (diet therapy group, baseline vs 12 months: 40 ± 4 vs 24 ± 3 ng/mL, P = 0.001; diet-plus-statin therapy, 46 ± 7 vs 34�

Natural Allelic Variations in Highly Polyploidy Saccharum Complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Jian; Yang, Xiping; Resende, Jr., Marcio F. R.

Sugarcane ( Saccharum spp.) is an important sugar and biofuel crop with high polyploid and complex genomes. The Saccharum complex, comprised of Saccharum genus and a few related genera, are important genetic resources for sugarcane breeding. A large amount of natural variation exists within the Saccharum complex. Though understanding their allelic variation has been challenging, it is critical to dissect allelic structure and to identify the alleles controlling important traits in sugarcane. To characterize natural variations in Saccharum complex, a target enrichment sequencing approach was used to assay 12 representative germplasm accessions. In total, 55,946 highly efficient probes were designedmore » based on the sorghum genome and sugarcane unigene set targeting a total of 6 Mb of the sugarcane genome. A pipeline specifically tailored for polyploid sequence variants and genotype calling was established. BWAmem and sorghum genome approved to be an acceptable aligner and reference for sugarcane target enrichment sequence analysis, respectively. Genetic variations including 1,166,066 non-redundant SNPs, 150,421 InDels, 919 gene copy number variations, and 1,257 gene presence/absence variations were detected. SNPs from three different callers (Samtools, Freebayes, and GATK) were compared and the validation rates were nearly 90%. Based on the SNP loci of each accession and their ploidy levels, 999,258 single dosage SNPs were identified and most loci were estimated as largely homozygotes. An average of 34,397 haplotype blocks for each accession was inferred. The highest divergence time among the Saccharum spp. was estimated as 1.2 million years ago (MYA). Saccharum spp. diverged from Erianthus and Sorghum approximately 5 and 6 MYA, respectively. Furthermore, the target enrichment sequencing approach provided an effective way to discover and catalog natural allelic variation in highly polyploid or heterozygous genomes.« less

Natural Allelic Variations in Highly Polyploidy Saccharum Complex

DOE PAGES

Song, Jian; Yang, Xiping; Resende, Jr., Marcio F. R.; ...

2016-06-08

Sugarcane ( Saccharum spp.) is an important sugar and biofuel crop with high polyploid and complex genomes. The Saccharum complex, comprised of Saccharum genus and a few related genera, are important genetic resources for sugarcane breeding. A large amount of natural variation exists within the Saccharum complex. Though understanding their allelic variation has been challenging, it is critical to dissect allelic structure and to identify the alleles controlling important traits in sugarcane. To characterize natural variations in Saccharum complex, a target enrichment sequencing approach was used to assay 12 representative germplasm accessions. In total, 55,946 highly efficient probes were designedmore » based on the sorghum genome and sugarcane unigene set targeting a total of 6 Mb of the sugarcane genome. A pipeline specifically tailored for polyploid sequence variants and genotype calling was established. BWAmem and sorghum genome approved to be an acceptable aligner and reference for sugarcane target enrichment sequence analysis, respectively. Genetic variations including 1,166,066 non-redundant SNPs, 150,421 InDels, 919 gene copy number variations, and 1,257 gene presence/absence variations were detected. SNPs from three different callers (Samtools, Freebayes, and GATK) were compared and the validation rates were nearly 90%. Based on the SNP loci of each accession and their ploidy levels, 999,258 single dosage SNPs were identified and most loci were estimated as largely homozygotes. An average of 34,397 haplotype blocks for each accession was inferred. The highest divergence time among the Saccharum spp. was estimated as 1.2 million years ago (MYA). Saccharum spp. diverged from Erianthus and Sorghum approximately 5 and 6 MYA, respectively. Furthermore, the target enrichment sequencing approach provided an effective way to discover and catalog natural allelic variation in highly polyploid or heterozygous genomes.« less

The positive association of branched-chain amino acids and metabolic dyslipidemia in Chinese Han population.

PubMed

Yang, Panpan; Hu, Wen; Fu, Zhenzhen; Sun, Luning; Zhou, Ying; Gong, Yingyun; Yang, Tao; Zhou, Hongwen

2016-07-25

It has been suggested that serum branched-chain amino acids (BCAAs) are associated with the incident, progression and prognostic of type 2 diabetes. However, the role of BCAAs in metabolic dyslipidemia (raised triglycerides (TG) and reduced high-density lipoprotein cholesterol (HDL-C)) remains poorly understood. This study aims to investigate 1) the association of serum BCAAs with total cholesterol (TC), TG, HDL-C and low-density lipoprotein cholesterol (LDL-C) and 2) the association between serum BCAAs levels and risk of metabolic dyslipidemia in a community population with different glucose homeostasis. Demographics data and blood samples were collected from 2251 Chinese subjects from the Huaian Diabetes Protective Program (HADPP) study. After exclusion for cardiovascular disease (CVD), serious hepatic or nephritic diseases and others, 1320 subjects remained for analysis (789 subjects with hemoglobin A1c (HbA1c) > 5.7, 521 with HbA1c ≤ 5.7). Serum BCAAs level was measured by liquid chromatography-tandem mass spectrometry (LC MS/MS). The association of BCAAs with lipids or with the risk of metabolic dyslipidemia was analyzed. Elevated serum BCAAs (both total and individual BCAA) were positively associated with TG and inversely associated with HDL-C in the whole population. These correlations were still significant even after adjustment for confounding factors (r = 0.165, p < 0.001 for TG; and r = -0.126, p < 0.001 for HDL-C). For reduced HDL-C, we found higher odds risk (OR) of Valine (Val) in high HbA1c group than in the low one (OR = 1.055, p < 0.001 vs OR = 1.032, p = 0.059). Compared with that in the first quartile, the multivariable-adjusted OR (95 % CI) of the 4(th) quartile of serum total BCAAs level for reduced HDL-C was 3.689 (2.325, 5.854) in high HbA1c group and 2.329 (1.284, 4.227) in low group, for raised TG was 3.305 (2.120, 5.152) and 2.972 (1.706, 5.176), and for metabolic dyslipidemia was 3.703 (2.261, 6

Adaptation of Drosophila to a novel laboratory environment reveals temporally heterogeneous trajectories of selected alleles.

PubMed

Orozco-terWengel, Pablo; Kapun, Martin; Nolte, Viola; Kofler, Robert; Flatt, Thomas; Schlötterer, Christian

2012-10-01

The genomic basis of adaptation to novel environments is a fundamental problem in evolutionary biology that has gained additional importance in the light of the recent global change discussion. Here, we combined laboratory natural selection (experimental evolution) in Drosophila melanogaster with genome-wide next generation sequencing of DNA pools (Pool-Seq) to identify alleles that are favourable in a novel laboratory environment and traced their trajectories during the adaptive process. Already after 15 generations, we identified a pronounced genomic response to selection, with almost 5000 single nucleotide polymorphisms (SNP; genome-wide false discovery rates < 0.005%) deviating from neutral expectation. Importantly, the evolutionary trajectories of the selected alleles were heterogeneous, with the alleles falling into two distinct classes: (i) alleles that continuously rise in frequency; and (ii) alleles that at first increase rapidly but whose frequencies then reach a plateau. Our data thus suggest that the genomic response to selection can involve a large number of selected SNPs that show unexpectedly complex evolutionary trajectories, possibly due to nonadditive effects. © 2012 Blackwell Publishing Ltd.

Contribution of 20 single nucleotide polymorphisms of 13 genes to dyslipidemia associated with antiretroviral therapy.

PubMed

Arnedo, Mireia; Taffé, Patrick; Sahli, Roland; Furrer, Hansjakob; Hirschel, Bernard; Elzi, Luigia; Weber, Rainer; Vernazza, Pietro; Bernasconi, Enos; Darioli, Roger; Bergmann, Sven; Beckmann, Jacques S; Telenti, Amalio; Tarr, Philip E

2007-09-01

HIV-1 infected individuals have an increased cardiovascular risk which is partially mediated by dyslipidemia. Single nucleotide polymorphisms in multiple genes involved in lipid transport and metabolism are presumed to modulate the risk of dyslipidemia in response to antiretroviral therapy. The contribution to dyslipidemia of 20 selected single nucleotide polymorphisms of 13 genes reported in the literature to be associated with plasma lipid levels (ABCA1, ADRB2, APOA5, APOC3, APOE, CETP, LIPC, LIPG, LPL, MDR1, MTP, SCARB1, and TNF) was assessed by longitudinally modeling more than 4400 plasma lipid determinations in 438 antiretroviral therapy-treated participants during a median period of 4.8 years. An exploratory genetic score was tested that takes into account the cumulative contribution of multiple gene variants to plasma lipids. Variants of ABCA1, APOA5, APOC3, APOE, and CETP contributed to plasma triglyceride levels, particularly in the setting of ritonavir-containing antiretroviral therapy. Variants of APOA5 and CETP contributed to high-density lipoprotein-cholesterol levels. Variants of CETP and LIPG contributed to non-high-density lipoprotein-cholesterol levels, a finding not reported previously. Sustained hypertriglyceridemia and low high-density lipoprotein-cholesterol during the study period was significantly associated with the genetic score. Single nucleotide polymorphisms of ABCA1, APOA5, APOC3, APOE, and CETP contribute to plasma triglyceride and high-density lipoprotein-cholesterol levels during antiretroviral therapy exposure. Genetic profiling may contribute to the identification of patients at risk for antiretroviral therapy-related dyslipidemia.

Peripheral subnuclear positioning suppresses Tcrb recombination and segregates Tcrb alleles from RAG2.

PubMed

Chan, Elizabeth A W; Teng, Grace; Corbett, Elizabeth; Choudhury, Kingshuk Roy; Bassing, Craig H; Schatz, David G; Krangel, Michael S

2013-11-26

Allelic exclusion requires that the two alleles at antigen-receptor loci attempt to recombine variable (V), diversity (D), and joining (J) gene segments [V(D)J recombination] asynchronously in nuclei of developing lymphocytes. It previously was shown that T-cell receptor β (Tcrb) alleles frequently and stochastically associate with the nuclear lamina and pericentromeric heterochromatin in CD4(-)CD8(-) thymocytes. Moreover, rearranged alleles were underrepresented at these locations. Here we used 3D immunofluorescence in situ hybridization to identify recently rearranged Tcrb alleles based on the accumulation of the DNA-repair protein 53BP1. We found that Tcrb alleles recombine asynchronously in double-negative thymocytes and that V(D)J recombination is suppressed on peripheral as compared with central Tcrb alleles. Moreover, the recombination events that did take place at the nuclear periphery preferentially occurred on Tcrb alleles that were partially dissociated from the nuclear lamina. To understand better the mechanism by which V(D)J recombination is suppressed at the nuclear periphery, we evaluated the subnuclear distribution of recombination-activating gene 2 (RAG2) protein. We found that RAG2 abundance was reduced at the nuclear periphery. Moreover, RAG2 was distributed differently from RNA polymerase II and histone H3K4 trimethylation. Our data suggest that the nuclear periphery suppresses V(D)J recombination, at least in part, by segregating Tcrb alleles from RAG proteins.

Characterization of new allele influencing flowering time in bread wheat introgressed from Triticum militinae.

PubMed

Ivaničová, Zuzana; Jakobson, Irena; Reis, Diana; Šafář, Jan; Milec, Zbyněk; Abrouk, Michael; Doležel, Jaroslav; Järve, Kadri; Valárik, Miroslav

2016-09-25

Flowering time variation was identified within a mapping population of doubled haploid lines developed from a cross between the introgressive line 8.1 and spring bread wheat cv. Tähti. The line 8.1 carried introgressions from tetraploid Triticum militinae in the cv. Tähti genetic background on chromosomes 1A, 2A, 4A, 5A, 7A, 1B and 5B. The most significant QTL for the flowering time variation was identified within the introgressed region on chromosome 5A and its largest effect was associated with the VRN-A1 locus, accounting for up to 70% of phenotypic variance. The allele of T. militinae origin was designated as VRN-A1f-like. The effect of the VRN-A1f-like allele was verified in two other mapping populations. QTL analysis identified that in cv. Tähti and cv. Mooni genetic background, VRN-A1f-like allele incurred a delay of 1.9-18.6 days in flowering time, depending on growing conditions. Sequence comparison of the VRN-A1f-like and VRN-A1a alleles from the parental lines of the mapping populations revealed major mutations in the promoter region as well as in the first intron, including insertion of a MITE element and a large deletion. The sequence variation allowed construction of specific diagnostic PCR markers for VRN-A1f-like allele determination. Identification and quantification of the effect of the VRN-A1f-like allele offers a useful tool for wheat breeding and for studying fine-scale regulation of flowering pathways in wheat. Copyright © 2016 Elsevier B.V. All rights reserved.

Mutant power: using mutant allele collections for yeast functional genomics.

PubMed

Norman, Kaitlyn L; Kumar, Anuj

2016-03-01

The budding yeast has long served as a model eukaryote for the functional genomic analysis of highly conserved signaling pathways, cellular processes and mechanisms underlying human disease. The collection of reagents available for genomics in yeast is extensive, encompassing a growing diversity of mutant collections beyond gene deletion sets in the standard wild-type S288C genetic background. We review here three main types of mutant allele collections: transposon mutagen collections, essential gene collections and overexpression libraries. Each collection provides unique and identifiable alleles that can be utilized in genome-wide, high-throughput studies. These genomic reagents are particularly informative in identifying synthetic phenotypes and functions associated with essential genes, including those modeled most effectively in complex genetic backgrounds. Several examples of genomic studies in filamentous/pseudohyphal backgrounds are provided here to illustrate this point. Additionally, the limitations of each approach are examined. Collectively, these mutant allele collections in Saccharomyces cerevisiae and the related pathogenic yeast Candida albicans promise insights toward an advanced understanding of eukaryotic molecular and cellular biology. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Fibrates are an essential part of modern anti-dyslipidemic arsenal: spotlight on atherogenic dyslipidemia and residual risk reduction.

PubMed

Tenenbaum, Alexander; Fisman, Enrique Z

2012-10-11

Currently the world faces epidemic of several closely related conditions: obesity, metabolic syndrome and type 2 diabetes (T2DM). The lipid profile of these patients and those with metabolic syndrome is characterized by the concurrent presence of qualitative as well as quantitative lipoprotein abnormalities: low levels of HDL, increased triglycerides, and prevalence of LDL particles that are smaller and denser than normal. This lipid phenotype has been defined as atherogenic dyslipidemia. Overwhelming evidences demonstrate that all components of the atherogenic dyslipidemia are important risk-factors for cardiovascular diseases. Optimal reduction of cardiovascular risk through comprehensive management of atherogenic dyslipidemias basically depends of the presence of efficacious lipid-modulating agents (beyond statin-based reduction of LDL-C). The most important class of medications which can be effectively used nowadays to combat atherogenic dyslipidemias is the fibrates. From a clinical point of view, in all available 5 randomized control trials beneficial effects of major fibrates (gemfibrozil, fenofibrate, bezafibrate) were clearly demonstrated and were highly significant in patients with atherogenic dyslipidemia. In these circumstances, the main determinant of the overall results of the trial is mainly dependent of the number of the included appropriate patients with atherogenic dyslipidemia. In a meta-analysis of dyslipidemic subgroups totaling 4726 patients a significant 35% relative risk reduction in cardiovascular events was observed compared with a non significant 6% reduction in those without dyslipidemia. However, different fibrates may have a somewhat different spectrum of effects. Currently only fenofibrate was investigated and proved to be effective in reducing microvascular complications of diabetes. Bezafibrate reduced the severity of intermittent claudication. Cardinal differences between bezafibrate and other fibrates are related to the effects on

Fibrates are an essential part of modern anti-dyslipidemic arsenal: spotlight on atherogenic dyslipidemia and residual risk reduction

PubMed Central

2012-01-01

Currently the world faces epidemic of several closely related conditions: obesity, metabolic syndrome and type 2 diabetes (T2DM). The lipid profile of these patients and those with metabolic syndrome is characterized by the concurrent presence of qualitative as well as quantitative lipoprotein abnormalities: low levels of HDL, increased triglycerides, and prevalence of LDL particles that are smaller and denser than normal. This lipid phenotype has been defined as atherogenic dyslipidemia. Overwhelming evidences demonstrate that all components of the atherogenic dyslipidemia are important risk-factors for cardiovascular diseases. Optimal reduction of cardiovascular risk through comprehensive management of atherogenic dyslipidemias basically depends of the presence of efficacious lipid-modulating agents (beyond statin-based reduction of LDL-C). The most important class of medications which can be effectively used nowadays to combat atherogenic dyslipidemias is the fibrates. From a clinical point of view, in all available 5 randomized control trials beneficial effects of major fibrates (gemfibrozil, fenofibrate, bezafibrate) were clearly demonstrated and were highly significant in patients with atherogenic dyslipidemia. In these circumstances, the main determinant of the overall results of the trial is mainly dependent of the number of the included appropriate patients with atherogenic dyslipidemia. In a meta-analysis of dyslipidemic subgroups totaling 4726 patients a significant 35% relative risk reduction in cardiovascular events was observed compared with a non significant 6% reduction in those without dyslipidemia. However, different fibrates may have a somewhat different spectrum of effects. Currently only fenofibrate was investigated and proved to be effective in reducing microvascular complications of diabetes. Bezafibrate reduced the severity of intermittent claudication. Cardinal differences between bezafibrate and other fibrates are related to the effects on

The Equilibrium Allele Frequency Distribution for a Population with Reproductive Skew

PubMed Central

Der, Ricky; Plotkin, Joshua B.

2014-01-01

We study the population genetics of two neutral alleles under reversible mutation in a model that features a skewed offspring distribution, called the Λ-Fleming–Viot process. We describe the shape of the equilibrium allele frequency distribution as a function of the model parameters. We show that the mutation rates can be uniquely identified from this equilibrium distribution, but the form of the offspring distribution cannot itself always be so identified. We introduce an estimator for the mutation rate that is consistent, independent of the form of reproductive skew. We also introduce a two-allele infinite-sites version of the Λ-Fleming–Viot process, and we use it to study how reproductive skew influences standing genetic diversity in a population. We derive asymptotic formulas for the expected number of segregating sites as a function of sample size and offspring distribution. We find that the Wright–Fisher model minimizes the equilibrium genetic diversity, for a given mutation rate and variance effective population size, compared to all other Λ-processes. PMID:24473932

The pluripotential effects of hypolipidemic treatment for polycystic ovary syndrome (PCOS): dyslipidemia, cardiovascular risk factors and beyond.

PubMed

Economou, Frangiskos; Xyrafis, Xenofon; Christakou, Charikleia; Diamanti-Kandarakis, Evanthia

2011-01-01

Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome characterized by oligo- or anovulation, clinical and/or biochemical signs of hyperandrogenemia and polycystic ovaries. Clinical expression is determined by both genetic and environmental factors. Dyslipidemia is very common in lean as well as in obese women with PCOS and should be considered in the therapeutic management of the syndrome. Additionally to dyslipidemia, other risk factors for cardiovascular disease strongly associated with PCOS include insulin resistance, impaired glucose tolerance and metabolic syndrome. Therefore, the ideal therapeutic approach for PCOS would be multi targeted treatment ameliorating not only ovarian dysfunction but also cardiometabolic aspects, including dyslipidemia. Recently, a new era of hypolipidemic agents like statins has been initiated with regard to PCOS. The spectrum of statins' targets has been expanded and in vitro and in vivo studies have explored the specific effect of statins on androgen production, insulin resistance and inflammatory markers in PCOS. Statins are potentially promising therapeutic agents targeting hormonal and metabolic disturbances in PCOS, though conclusive results are still pending. Since several hormonal and metabolic aberrations characterizing this multifaceted syndrome cluster and interact with each other, their effects on the lipid profile are interweaving and the therapeutic modalities targeting dyslipidemia appear to have a more broad beneficial effect.

Gene expression allelic imbalance in ovine brown adipose tissue impacts energy homeostasis

PubMed Central

Ghazanfar, Shila; Vuocolo, Tony; Morrison, Janna L.; Nicholas, Lisa M.; McMillen, Isabella C.; Yang, Jean Y. H.; Buckley, Michael J.

2017-01-01

Heritable trait variation within a population of organisms is largely governed by DNA variations that impact gene transcription and protein function. Identifying genetic variants that affect complex functional traits is a primary aim of population genetics studies, especially in the context of human disease and agricultural production traits. The identification of alleles directly altering mRNA expression and thereby biological function is challenging due to difficulty in isolating direct effects of cis-acting genetic variations from indirect trans-acting genetic effects. Allele specific gene expression or allelic imbalance in gene expression (AI) occurring at heterozygous loci provides an opportunity to identify genes directly impacted by cis-acting genetic variants as indirect trans-acting effects equally impact the expression of both alleles. However, the identification of genes showing AI in the context of the expression of all genes remains a challenge due to a variety of technical and statistical issues. The current study focuses on the discovery of genes showing AI using single nucleotide polymorphisms as allelic reporters. By developing a computational and statistical process that addressed multiple analytical challenges, we ranked 5,809 genes for evidence of AI using RNA-Seq data derived from brown adipose tissue samples from a cohort of late gestation fetal lambs and then identified a conservative subgroup of 1,293 genes. Thus, AI was extensive, representing approximately 25% of the tested genes. Genes associated with AI were enriched for multiple Gene Ontology (GO) terms relating to lipid metabolism, mitochondrial function and the extracellular matrix. These functions suggest that cis-acting genetic variations causing AI in the population are preferentially impacting genes involved in energy homeostasis and tissue remodelling. These functions may contribute to production traits likely to be under genetic selection in the population. PMID:28665992

[Recommendations of the European Society of Cardiology and the European Atherosclerosis Society on Cardiovascular Disease Prevention and Management of Dyslipidemias. for the Diagnosis of Atherosclerosis and Dyslipidemia Treatment (2016): Basic S.G.

PubMed

Bubnova, M G; Kukharchuk, V V

2017-03-01

This review summarizes the main provisions of the new, issued in 2016, recommendations of the European Society of Cardiology and Atherosclerosis Society in cooperation with the European Association on Cardiovascular Prevention and Rehabilitation on Cardiovascular disease prevention and Management of dyslipidemia. In these recommendations, the following trends can be traced distinctly: priority in primary prevention is given to non-drug methods of influence; targets of hypolipidemic therapy are identified not only for low density lipoprotein (LDL) cholesterol (CH), but also for non-high density lipoprotein (HDL) CH, especially in cases of concomitant hypertriglyceridemia. In the field of therapy, in which statins remain the main tool of correction of hyperlipidemia, it is recommended to more widely resort to the use of combination therapy, especially in cases of familial hypercholesterolemia or intolerance to statins; introduction of a new class of drugs- inhibitors of proprotein convertase subtilisin/kexin type 9 makes it possible to further reduce the level of LDLCH, lipoprotein(a) more than 60%. Regarding the wider application of these drugs there are issues related to the relatively limited experience of their use and the lack of data on long-term results and the incidence of side effects. Much attention is paid to more active correction of dyslipidemia in elderly patients, patients with chronic renal failure, diabetes, and several other diseases. The emergence of new European recommendations will undoubtedly serve as a stimulus to the revision of the Russian recommendations, which remain unchanged from 2012.

Lipid Screening in Childhood and Adolescence for Detection of Multifactorial Dyslipidemia: Evidence Report and Systematic Review for the US Preventive Services Task Force.

PubMed

Lozano, Paula; Henrikson, Nora B; Morrison, Caitlin C; Dunn, John; Nguyen, Matt; Blasi, Paula R; Whitlock, Evelyn P

2016-08-09

a low-fat, low-cholesterol diet on lipid levels at 1 year in children aged 8 to 10 years with mild to moderate dyslipidemia; mean between-group difference in TC change from baseline was -6.1 mg/dL (95% CI, -9.1 to -3.2 mg/dL; P < .001). Between-group differences dissipated by year 5. The intervention did not adversely affect nutritional status, growth, or development over the 18-year study period. One observational study (n = 9245) found that TC concentration at age 12 to 39 years was not associated with death before age 55 years. The diagnostic yield of lipid screening varies by age and body mass index. No direct evidence was identified for benefits or harms of childhood screening or treatment on outcomes in adulthood. Intensive dietary interventions may be safe, with modest short-term benefit of uncertain clinical significance.

Nomenclature for alleles of the thiopurine methyltransferase gene

PubMed Central

Appell, Malin L.; Berg, Jonathan; Duley, John; Evans, William E.; Kennedy, Martin A.; Lennard, Lynne; Marinaki, Tony; McLeod, Howard L.; Relling, Mary V.; Schaeffeler, Elke; Schwab, Matthias; Weinshilboum, Richard; Yeoh, Allen E.J.; McDonagh, Ellen M.; Hebert, Joan M.; Klein, Teri E.; Coulthard, Sally A.

2013-01-01

The drug-metabolizing enzyme thiopurine methyltransferase (TPMT) has become one of the best examples of pharmacogenomics to be translated into routine clinical practice. TPMT metabolizes the thiopurines 6-mercaptopurine, 6-thioguanine, and azathioprine, drugs that are widely used for treatment of acute leukemias, inflammatory bowel diseases, and other disorders of immune regulation. Since the discovery of genetic polymorphisms in the TPMT gene, many sequence variants that cause a decreased enzyme activity have been identified and characterized. Increasingly, to optimize dose, pretreatment determination of TPMT status before commencing thiopurine therapy is now routine in many countries. Novel TPMT sequence variants are currently numbered sequentially using PubMed as a source of information; however, this has caused some problems as exemplified by two instances in which authors’ articles appeared on PubMed at the same time, resulting in the same allele numbers given to different polymorphisms. Hence, there is an urgent need to establish an order and consensus to the numbering of known and novel TPMT sequence variants. To address this problem, a TPMT nomenclature committee was formed in 2010, to define the nomenclature and numbering of novel variants for the TPMT gene. A website (http://www.imh.liu.se/tpmtalleles) serves as a platform for this work. Researchers are encouraged to submit novel TPMT alleles to the committee for designation and reservation of unique allele numbers. The committee has decided to renumber two alleles: nucleotide position 106 (G > A) from TPMT*24 to TPMT*30 and position 611 (T > C, rs79901429) from TPMT*28 to TPMT*31. Nomenclature for all other known alleles remains unchanged. PMID:23407052

Prevalence of atherogenic dyslipidemia in primary care patients at moderate-very high risk of cardiovascular disease. Cardiovascular risk perception.

PubMed

Plana, Nuria; Ibarretxe, Daiana; Cabré, Anna; Ruiz, Emilio; Masana, Lluis

2014-01-01

Atherogenic dyslipidemia is an important risk factor for cardiovascular disease. We aim to determine atherogenic dyslipidemia prevalence in primary care patients at moderate-very high cardiovascular risk and its associated cardiovascular risk perception in Spain. This cross-sectional study included 1137 primary care patients. Patients had previous cardiovascular disease, diabetes mellitus, SCORE risk ≥ 3, severe hypertension or dyslipidemia. Atherogenic dyslipidemia was defined as low HDL-C (<40 mg/dL [males], <50 mg/dL [females]) and elevated triglycerides (≥ 150 mg/dL). A visual analog scale was used to define a perceived cardiovascular disease risk score. Mean age was 63.9 ± 9.7 years (64.6% males). The mean BMI was 29.1 ± 4.3 kg/m(2), and mean waist circumference 104.2 ± 12.7 cm (males), and 97.2 ± 14.0 cm (females). 29.4% were smokers, 76.4% had hypertension, 48.0% were diabetics, 24.7% had previous myocardial infarction, and 17.8% peripheral arterial disease. European guidelines classified 83.6% at very high cardiovascular risk. Recommended HDL-C levels were achieved by 50.1% of patients and 37.3% had triglycerides in the reference range. Target LDL-C was achieved by 8.8%. The overall atherogenic dyslipidemia prevalence was 27.1% (34.1% in diabetics). This prevalence in patients achieving target LDL-C was 21.4%. Cardiovascular risk perceived by patients was 4.3/10, while primary care physicians scored 5.7/10. When LDL-C levels are controlled, atherogenic dyslipidemia is more prevalent in those patients at highest cardiovascular risk and with diabetes. This highlights the importance of intervention strategies to prevent the residual vascular risk in this population. Both patients and physicians underestimated cardiovascular risk. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

The Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus Pandemic: II. Therapeutic Management of Atherogenic Dyslipidemia

PubMed Central

Ginsberg, Henry N.; MacCallum, Paul R.

2010-01-01

Strategies for the effective management of cardiovascular risk factors in patients with the metabolic syndrome (MS) or type 2 diabetes mellitus (T2DM) are essential to help reduce cardiovascular morbidity and mortality. Treatment strategies should be multi-factorial and include the promotion of therapeutic lifestyle changes, as well as pharmacologic therapies to treat individual risk factors according to current guidelines. In an accompanying article, the importance of atherogenic dyslipidemia as a risk factor for the development of cardiovascular disease in patients with the MS or T2DM was highlighted. Current treatment options for managing this characteristic form of atherogenic dyslipidemia are limited and tend to be only moderately effective. The focus of this review is the current pharmacotherapies available for the management of atherogenic dyslipidemia in patients with the MS or T2DM, highlighting the rationale for combining available treatments. Novel strategies currently in clinical development are also discussed. PMID:19751468

Comparison of the efficacy of liraglutide with pioglitazone on dexamethasone induced hepatic steatosis, dyslipidemia and hyperglycaemia in albino rats.

PubMed

Vinodraj, K; Nagendra Nayak, I M; Rao, J Vikram; Mathai, Paul; Chandralekha, N; Nitasha, B; Rajesh, D; Chethan, T K

2015-01-01

To evaluate the efficacy of liraglutide with pioglitazone for prevention of dexamethasone induced hepatic steatosis, dyslipidemia and hyperglycemia in Albino rats. There were four groups of six rats each. First group received dexamethasone alone in a dose of 8 mg/kg intraperitoneally for 6 days to induce metabolic changes and considered as dexamethasone control. Second group received liraglutide 1.8 mg/kg subcutaneously 6 days before dexamethasone and 6 days during dexamethasone administration. Third group received pioglitazone 45 mg/kg orally 6 days before dexamethasone and 6 days during dexamethasone administration. Fourth group did not receive any medication and was considered as normal control. Fasting blood sugar, lipid profile, blood sugar 2 h after glucose load were measured. Liver weight, liver volume, and histopathological analysis were done. Dexamethasone caused hepatomegaly, dyslipidemia, and hyperglycemia. Both pioglitazone and liraglutide significantly reduced hepatomegaly, dyslipidemia and hyperglycemia (P < 0.01). Reduction of blood sugar levels after glucose load was significant with pioglitazone when compared with liraglutide (P < 0.01). Liraglutide has comparable efficacy to pioglitazone in prevention of dexamethasone induced hepatomegaly, dyslipidemia and fasting hyperglycemia.

Amerindian-specific regions under positive selection harbour new lipid variants in Latinos

PubMed Central

Ko, Arthur; Cantor, Rita M.; Weissglas-Volkov, Daphna; Nikkola, Elina; Reddy, Prasad M. V. Linga; Sinsheimer, Janet S.; Pasaniuc, Bogdan; Brown, Robert; Alvarez, Marcus; Rodriguez, Alejandra; Rodriguez-Guillen, Rosario; Bautista, Ivette C.; Arellano-Campos, Olimpia; Muñoz-Hernández, Linda L.; Salomaa, Veikko; Kaprio, Jaakko; Jula, Antti; Jauhiainen, Matti; Heliövaara, Markku; Raitakari, Olli; Lehtimäki, Terho; Eriksson, Johan G.; Perola, Markus; Lohmueller, Kirk E.; Matikainen, Niina; Taskinen, Marja-Riitta; Rodriguez-Torres, Maribel; Riba, Laura; Tusie-Luna, Teresa; Aguilar-Salinas, Carlos A.; Pajukanta, Päivi

2014-01-01

Dyslipidemia and obesity are especially prevalent in populations with Amerindian backgrounds, such as Mexican–Americans, which predispose these populations to cardiovascular disease. Here we design an approach, known as the cross-population allele screen (CPAS), which we conduct prior to a genome-wide association study (GWAS) in 19,273 Europeans and Mexicans, in order to identify Amerindian risk genes in Mexicans. Utilizing CPAS to restrict the GWAS input variants to only those differing in frequency between the two populations, we identify novel Amerindian lipid genes, receptor-related orphan receptor alpha (RORA) and salt-inducible kinase 3 (SIK3), and three loci previously unassociated with dyslipidemia or obesity. We also detect lipoprotein lipase (LPL) and apolipoprotein A5 (APOA5) harbouring specific Amerindian signatures of risk variants and haplotypes. Notably, we observe that SIK3 and one novel lipid locus underwent positive selection in Mexicans. Furthermore, after a high-fat meal, the SIK3 risk variant carriers display high triglyceride levels. These findings suggest that Amerindian-specific genetic architecture leads to a higher incidence of dyslipidemia and obesity in modern Mexicans. PMID:24886709

Peripheral subnuclear positioning suppresses Tcrb recombination and segregates Tcrb alleles from RAG2

PubMed Central

Chan, Elizabeth A. W.; Teng, Grace; Corbett, Elizabeth; Choudhury, Kingshuk Roy; Bassing, Craig H.; Schatz, David G.; Krangel, Michael S.

2013-01-01

Allelic exclusion requires that the two alleles at antigen-receptor loci attempt to recombine variable (V), diversity (D), and joining (J) gene segments [V(D)J recombination] asynchronously in nuclei of developing lymphocytes. It previously was shown that T-cell receptor β (Tcrb) alleles frequently and stochastically associate with the nuclear lamina and pericentromeric heterochromatin in CD4−CD8− thymocytes. Moreover, rearranged alleles were underrepresented at these locations. Here we used 3D immunofluorescence in situ hybridization to identify recently rearranged Tcrb alleles based on the accumulation of the DNA-repair protein 53BP1. We found that Tcrb alleles recombine asynchronously in double-negative thymocytes and that V(D)J recombination is suppressed on peripheral as compared with central Tcrb alleles. Moreover, the recombination events that did take place at the nuclear periphery preferentially occurred on Tcrb alleles that were partially dissociated from the nuclear lamina. To understand better the mechanism by which V(D)J recombination is suppressed at the nuclear periphery, we evaluated the subnuclear distribution of recombination-activating gene 2 (RAG2) protein. We found that RAG2 abundance was reduced at the nuclear periphery. Moreover, RAG2 was distributed differently from RNA polymerase II and histone H3K4 trimethylation. Our data suggest that the nuclear periphery suppresses V(D)J recombination, at least in part, by segregating Tcrb alleles from RAG proteins. PMID:24218622

Atherogenic dyslipidemia and risk of silent coronary artery disease in asymptomatic patients with type 2 diabetes: a cross-sectional study.

PubMed

Valensi, Paul; Avignon, Antoine; Sultan, Ariane; Chanu, Bernard; Nguyen, Minh Tuan; Cosson, Emmanuel

2016-07-22

To investigate whether atherogenic dyslipidemia, a dyslipidemic profile combining elevated triglycerides and low high-density lipoprotein (HDL) cholesterol, is predictive of risk of silent myocardial ischemia (SMI) or angiographic coronary artery disease (CAD) in asymptomatic patients with type 2 diabetes. Cohort study in 1080 asymptomatic patients with type 2 diabetes with a normal resting electrocardiogram, at least one additional cardiovascular risk factor and low density lipoprotein (LDL) cholesterol <3.35 mmol/L. Patients initially underwent screening for SMI by stress myocardial scintigraphy. Patients with SMI underwent coronary angiography. Overall, 60 (5.5 %) patients had atherogenic dyslipidemia (triglycerides ≥2.26 mmol/L and HDL cholesterol ≤0.88 mmol/L). In multivariate analyses taking into account the parameters associated in univariate analyses with SMI and then CAD, atherogenic dyslipidemia was associated with SMI (odds ratio 1.8[1.0-3.3]), as were male gender (OR 2.1[1.5-2.9]), BMI (OR 0.97[0.94-0.997]), retinopathy (OR 1.4[1.1-1.9]), peripheral occlusive arterial disease (POAD: OR 2.5[1.6-3.8]) and mean blood pressure (OR 1.01[1.00-1.03]); atherogenic dyslipidemia was associated with CAD (OR 4.0[1.7-9.2]), as were male gender (OR 3.0[1.6-5.6]), BMI (OR 0.94[0.90-0.995]), retinopathy (OR 1.7[1.0-2.9], POAD (OR 4.0[2.1-7.4]) and mean blood pressure (OR 1.03[1.01-1.05]). In the subgroup of 584 patients with LDL cholesterol <2.6 mmol/L, atherogenic dyslipidemia was also associated with CAD (OR 3.6[1.5-9.0]). Atherogenic dyslipidemia was associated with an increased risk of SMI and silent CAD in patients with type 2 diabetes and LDL cholesterol levels <3.35 mmol/L. Specific management of atherogenic dyslipidemia might help reducing the high residual burden of cardiovascular disease.

Importance of high-density lipoprotein cholesterol levels in elderly diabetic individuals with type IIb dyslipidemia: A 2-year survey of cardiovascular events.

PubMed

Ina, Koichiro; Hayashi, Toshio; Araki, Atsushi; Kawashima, Seinosuke; Sone, Hirohito; Watanabe, Hiroshi; Ohrui, Takashi; Yokote, Koutaro; Takemoto, Minoru; Kubota, Kiyoshi; Noda, Mitsuhiko; Noto, Hiroshi; Ding, Qun-Fang; Zhang, Jie; Yu, Ze-Yun; Yoon, Byung-Koo; Nomura, Hideki; Kuzuya, Masafumi

2014-10-01

The risk factors for ischemic heart disease (IHD) or cerebrovascular accident (CVA) in elderly diabetic individuals with type IIb dyslipidemia are not fully known. Therefore, we investigated the relationship between lipid levels and IHD and CVA in diabetic individuals with type IIb dyslipidemia. The Japan Cholesterol and Diabetes Mellitus Study is a prospective cohort study of 4014 type 2 diabetic patients (1936 women; age 67.4 ± 9.5 years). The primary end-points were the onset of IHD or CVA. Lipid and glucose levels, and other factors were investigated in relation to the occurrence of IHD or CVA. A total of 462 participants were included in the group of patients with type IIb dyslipidemia. The 462 diabetic participants with type IIb dyslipidemia were divided into those who were aged <65 years, 65-74 years and >75 years (n=168, 190 and 104, respectively). High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol/HDL-C were significantly associated with the risk of cardiovascular events in diabetic individuals with type IIb dyslipidemia who were aged <65 years, and HDL-C and diastolic blood pressure was significantly associated with cardiovascular events in patients aged 65-74 years. Non-HDL-C was not significantly associated with the risk of cardiovascular events. Multiple regression analysis showed that lower HDL-C was significantly associated with the risk of cardiovascular events in diabetic individuals with type IIb dyslipidemia who were aged <65 years and 65-74 years. Lower HDL-C was an important risk factor for cardiovascular events in diabetic individuals with type IIb dyslipidemia who were aged <75 years. © 2013 Japan Geriatrics Society.

A novel FY*A allele with the 265T and 298A SNPs formerly associated exclusively with the FY*B allele and weak Fy(b) antigen expression: implication for genotyping interpretative algorithms.

PubMed

Lopez, G H; Condon, J A; Wilson, B; Martin, J R; Liew, Y-W; Flower, R L; Hyland, C A

2015-01-01

An Australian Caucasian blood donor consistently presented a serology profile for the Duffy blood group as Fy(a+b+) with Fy(a) antigen expression weaker than other examples of Fy(a+b+) red cells. Molecular typing studies were performed to investigate the reason for the observed serology profile. Blood group genotyping was performed using a commercial SNP microarray platform. Sanger sequencing was performed using primer sets to amplify across exons 1 and 2 of the FY gene and using allele-specific primers. The propositus was genotyped as FY*A/B, FY*X heterozygote that predicted the Fy(a+b+(w) ) phenotype. Sequencing identified the 265T and 298A variants on the FY*A allele. This link between FY*A allele and 265T was confirmed by allele-specific PCR. The reduced Fy(a) antigen reactivity is attributed to a FY*A allele-carrying 265T and 298A variants previously defined in combination only with the FY*B allele and associated with weak Fy(b) antigen expression. This novel allele should be considered in genotyping interpretative algorithms for generating a predicted phenotype. © 2014 International Society of Blood Transfusion.

CYP3A4 allelic variants with amino acid substitutions in exons 7 and 12: evidence for an allelic variant with altered catalytic activity.

PubMed

Sata, F; Sapone, A; Elizondo, G; Stocker, P; Miller, V P; Zheng, W; Raunio, H; Crespi, C L; Gonzalez, F J

2000-01-01

To determine the existence of mutant and variant CgammaP3A4 alleles in three racial groups and to assess functions of the variant alleles by complementary deoxyribonucleic acid (cDNA) expression. A bacterial artificial chromosome that contains the complete CgammaP3A4 gene was isolated and the exons and surrounding introns were directly sequenced to develop primers to polymerase chain reaction (PCR) amplify and sequence the gene from lymphocyte DNA. DNA samples from Chinese, black, and white subjects were screened. Mutating the affected amino acid in the wild-type cDNA and expressing the variant enzyme with use of the baculovirus system was used to functionally evaluate the variant allele having a missense mutation. To investigate the existence of mutant and variant CgammaP3A4 alleles in humans, all 13 exons and the 5'-flanking region of the human CgammaP3A4 gene in three racial groups were sequenced and four alleles were identified. An A-->G point mutation in the 5'-flanking region of the human CgammaP3A4 gene, designated CgammaP3A4*1B, was found in the three different racial groups. The frequency of this allele in a white population was 4.2%, whereas it was 66.7% in black subjects. The CgammaP3A4*1B allele was not found in Chinese subjects. A second variant allele, designated CgammaP3A4*2, having a Ser222Pro change, was found at a frequency of 2.7% in the white population and was absent in the black subjects and Chinese subjects analyzed. Baculovirus-directed cDNA expression revealed that the CYP3A4*2 P450 had a lower intrinsic clearance for the CYP3A4 substrate nifedipine compared with the wild-type enzyme but was not significantly different from the wild-type enzyme for testosterone 6beta-hydroxylation. Another rare allele, designated CgammaP3A4*3, was found in a single Chinese subject who had a Met445Thr change in the conserved heme-binding region of the P450. These are the first examples of potential function polymorphisms resulting from missense mutations in

Systematic Cell-Based Phenotyping of Missense Alleles Empowers Rare Variant Association Studies: A Case for LDLR and Myocardial Infarction

PubMed Central

Schuberth, Christian; Won, Hong-Hee; Blattmann, Peter; Joggerst-Thomalla, Brigitte; Theiss, Susanne; Asselta, Rosanna; Duga, Stefano; Merlini, Pier Angelica; Ardissino, Diego; Lander, Eric S.; Gabriel, Stacey; Rader, Daniel J.; Peloso, Gina M.; Kathiresan, Sekar; Runz, Heiko

2015-01-01

A fundamental challenge to contemporary genetics is to distinguish rare missense alleles that disrupt protein functions from the majority of alleles neutral on protein activities. High-throughput experimental tools to securely discriminate between disruptive and non-disruptive missense alleles are currently missing. Here we establish a scalable cell-based strategy to profile the biological effects and likely disease relevance of rare missense variants in vitro. We apply this strategy to systematically characterize missense alleles in the low-density lipoprotein receptor (LDLR) gene identified through exome sequencing of 3,235 individuals and exome-chip profiling of 39,186 individuals. Our strategy reliably identifies disruptive missense alleles, and disruptive-allele carriers have higher plasma LDL-cholesterol (LDL-C). Importantly, considering experimental data refined the risk of rare LDLR allele carriers from 4.5- to 25.3-fold for high LDL-C, and from 2.1- to 20-fold for early-onset myocardial infarction. Our study generates proof-of-concept that systematic functional variant profiling may empower rare variant-association studies by orders of magnitude. PMID:25647241

Estimated allele substitution effects underlying genomic evaluation models depend on the scaling of allele counts.

PubMed

Bouwman, Aniek C; Hayes, Ben J; Calus, Mario P L

2017-10-30

Genomic evaluation is used to predict direct genomic values (DGV) for selection candidates in breeding programs, but also to estimate allele substitution effects (ASE) of single nucleotide polymorphisms (SNPs). Scaling of allele counts influences the estimated ASE, because scaling of allele counts results in less shrinkage towards the mean for low minor allele frequency (MAF) variants. Scaling may become relevant for estimating ASE as more low MAF variants will be used in genomic evaluations. We show the impact of scaling on estimates of ASE using real data and a theoretical framework, and in terms of power, model fit and predictive performance. In a dairy cattle dataset with 630 K SNP genotypes, the correlation between DGV for stature from a random regression model using centered allele counts (RRc) and centered and scaled allele counts (RRcs) was 0.9988, whereas the overall correlation between ASE using RRc and RRcs was 0.27. The main difference in ASE between both methods was found for SNPs with a MAF lower than 0.01. Both the ratio (ASE from RRcs/ASE from RRc) and the regression coefficient (regression of ASE from RRcs on ASE from RRc) were much higher than 1 for low MAF SNPs. Derived equations showed that scenarios with a high heritability, a large number of individuals and a small number of variants have lower ratios between ASE from RRc and RRcs. We also investigated the optimal scaling parameter [from - 1 (RRcs) to 0 (RRc) in steps of 0.1] in the bovine stature dataset. We found that the log-likelihood was maximized with a scaling parameter of - 0.8, while the mean squared error of prediction was minimized with a scaling parameter of - 1, i.e., RRcs. Large differences in estimated ASE were observed for low MAF SNPs when allele counts were scaled or not scaled because there is less shrinkage towards the mean for scaled allele counts. We derived a theoretical framework that shows that the difference in ASE due to shrinkage is heavily influenced by the

Dyslipidemia and Food Security in Low-Income US Adolescents: National Health and Nutrition Examination Survey, 2003-2010.

PubMed

Tester, June M; Laraia, Barbara A; Leung, Cindy W; Mietus-Snyder, Michele L

2016-02-11

Low levels of food security are associated with dyslipidemia and chronic disease in adults, particularly in women. There is a gap in knowledge about the relationship between food security among youth and dyslipidemia and chronic disease. We investigated the relationship between food security status and dyslipidemia among low-income adolescents. We analyzed data from adolescents aged 12 to 18 years (N = 1,072) from households with incomes at or below 200% of the federal poverty level from the National Health and Nutrition Examination Survey (NHANES) 2003-2010. We used logistic regression to examine the relationship between household food security status and the odds of having abnormalities with fasting total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), serum triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), TG/HDL-C ratio, and apolipoprotein B (Apo B). Models included age, sex, race/ethnicity, smoking status, partnered status in the household, and maternal education, with additional adjustment for adiposity. Household food security status was not associated with elevated TC or LDL-C. Adolescents with marginal food security were more likely than food-secure peers to have elevated TGs (odds ratio [OR] = 1.86; 95% confidence interval [CI], 1.14-3.05), TG/HDL-C ratio (OR = 1.74; 95% CI, 1.11-2.82), and Apo B (OR = 1.98; 95% CI, 1.17-3.36). Female adolescents with marginal food security had greater odds than male adolescents of having low HDL-C (OR = 2.69; 95% CI, 1.14-6.37). No elevated odds of dyslipidemia were found for adolescents with low or very low food security. Adjustment for adiposity did not attenuate estimates. In this nationally representative sample, low-income adolescents living in households with marginal food security had increased odds of having a pattern consistent with atherogenic dyslipidemia, which represents a cardiometabolic burden above their risk from adiposity alone.

Identification of a new allele of Es-I segregating in an inbred strain of mice.

PubMed

Soares, E R

1979-08-01

A new allele of Es-1, designated Es-1e, has been identified in the mouse. This allele was discovered segregating among the progeny of a strain DBA/2J male and is apparently the result of a spontaneous mutation within this strain. Genetic analyses have shown that this mutation is heritable and, further, that both heterozygous and homozygous progeny are viable and fertile. To date, no discernible deleterious effects have been identified as associated with this mutation.

Lipid Profiles and APOE4 Allele Impact Midlife Cognitive Decline in HIV-Infected Men on Antiretroviral Therapy.

PubMed

Mukerji, Shibani S; Locascio, Joseph J; Misra, Vikas; Lorenz, David R; Holman, Alex; Dutta, Anupriya; Penugonda, Sudhir; Wolinsky, Steven M; Gabuzda, Dana

2016-10-15

Dyslipidemia and apolipoprotein E4 (APOE ϵ4) allele are risk factors for age-related cognitive decline, but how these risks are modified by human immunodeficiency virus (HIV) infection is unclear. In a longitudinal nested study from the Multicenter AIDS Cohort Study, 273 HIV type 1-infected (HIV(+)) men aged 50-65 years with baseline HIV RNA <400 copies/mL and on continuous antiretroviral therapy (ART) in ≥95% of follow-up visits were matched by sociodemographic variables to 516 HIV-uninfected (HIV(-)) controls. The association between lipid markers (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides), APOE genotype, and cognitive decline in HIV infection was examined using mixed-effects models. The median baseline age of participants was 51, 81% were white, and 89% had education >12 years. HIV(+) men had similar baseline total cholesterol and LDL-C, but lower HDL-C and higher triglycerides than controls (P < .001). Higher total cholesterol and LDL-C were associated with faster rates of cognitive decline (P < .01), whereas higher HDL-C attenuated decline (P = .02) in HIV(+) men. In HIV(+) men with elevated cholesterol, statin use was associated with a slower estimated rate of decline (P = .02). APOE ϵ4 genotype accelerated cognitive decline in HIV(+) but not HIV(-) men (P = .01), with trajectories diverging from HIV(-) ε4 carriers after age 50. Total cholesterol levels did not modify the association of ϵ4 genotype with decline (P = .9). Elevated cholesterol and APOE ϵ4 genotype are independent risk factors for cognitive decline in ART-adherent HIV(+) men aged >50 years. Treatment of dyslipidemia may be an effective strategy to reduce cognitive decline in older HIV(+) individuals. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Identification of multiple interacting alleles conferring low glycerol and high ethanol yield in Saccharomyces cerevisiae ethanolic fermentation

PubMed Central

2013-01-01

Background Genetic engineering of industrial microorganisms often suffers from undesirable side effects on essential functions. Reverse engineering is an alternative strategy to improve multifactorial traits like low glycerol/high ethanol yield in yeast fermentation. Previous rational engineering of this trait always affected essential functions like growth and stress tolerance. We have screened Saccharomyces cerevisiae biodiversity for specific alleles causing lower glycerol/higher ethanol yield, assuming higher compatibility with normal cellular functionality. Previous work identified ssk1E330N…K356N as causative allele in strain CBS6412, which displayed the lowest glycerol/ethanol ratio. Results We have now identified a unique segregant, 26B, that shows similar low glycerol/high ethanol production as the superior parent, but lacks the ssk1E330N…K356N allele. Using segregants from the backcross of 26B with the inferior parent strain, we applied pooled-segregant whole-genome sequence analysis and identified three minor quantitative trait loci (QTLs) linked to low glycerol/high ethanol production. Within these QTLs, we identified three novel alleles of known regulatory and structural genes of glycerol metabolism, smp1R110Q,P269Q, hot1P107S,H274Y and gpd1L164P as causative genes. All three genes separately caused a significant drop in the glycerol/ethanol production ratio, while gpd1L164P appeared to be epistatically suppressed by other alleles in the superior parent. The order of potency in reducing the glycerol/ethanol ratio of the three alleles was: gpd1L164P > hot1P107S,H274Y ≥ smp1R110Q,P269Q. Conclusions Our results show that natural yeast strains harbor multiple specific alleles of genes controlling essential functions, that are apparently compatible with survival in the natural environment. These newly identified alleles can be used as gene tools for engineering industrial yeast strains with multiple subtle changes, minimizing the risk of

Arsenic-induced dyslipidemia in male albino rats: comparison between trivalent and pentavalent inorganic arsenic in drinking water.

PubMed

Afolabi, Olusegun K; Wusu, Adedoja D; Ogunrinola, Olabisi O; Abam, Esther O; Babayemi, David O; Dosumu, Oluwatosin A; Onunkwor, Okechukwu B; Balogun, Elizabeth A; Odukoya, Olusegun O; Ademuyiwa, Oladipo

2015-06-05

dyslipidemia, our study identified two common denominators of dyslipidemia namely: inhibition of reverse cholesterol transport and increase in plasma FFA. These two denominators (in addition to other individual perturbations of lipid metabolism induced by each arsenical), suggest that in contrast to strengthening a dose-dependent effect phenomenon, the two forms of inorganic arsenic induced lipotoxic and non-lipotoxic dyslipidemia at "low" or "medium" doses and these might be responsible for the cardiovascular and other disease endpoints of inorganic arsenic exposure through drinking water.

Intrinsic MYH7 expression regulation contributes to tissue level allelic imbalance in hypertrophic cardiomyopathy.

PubMed

Montag, Judith; Syring, Mandy; Rose, Julia; Weber, Anna-Lena; Ernstberger, Pia; Mayer, Anne-Kathrin; Becker, Edgar; Keyser, Britta; Dos Remedios, Cristobal; Perrot, Andreas; van der Velden, Jolanda; Francino, Antonio; Navarro-Lopez, Francesco; Ho, Carolyn Yung; Brenner, Bernhard; Kraft, Theresia

2017-08-01

HCM, the most common inherited cardiac disease, is mainly caused by mutations in sarcomeric genes. More than a third of the patients are heterozygous for mutations in the MYH7 gene encoding for the β-myosin heavy chain. In HCM-patients, expression of the mutant and the wildtype allele can be unequal, thus leading to fractions of mutant and wildtype mRNA and protein which deviate from 1:1. This so-called allelic imbalance was detected in whole tissue samples but also in individual cells. There is evidence that the severity of HCM not only depends on the functional effect of the mutation itself, but also on the fraction of mutant protein in the myocardial tissue. Allelic imbalance has been shown to occur in a broad range of genes. Therefore, we aimed to examine whether the MYH7-alleles are intrinsically expressed imbalanced or whether the allelic imbalance is solely associated with the disease. We compared the expression of MYH7-alleles in non-HCM donors and in HCM-patients with different MYH7-missense mutations. In the HCM-patients, we identified imbalanced as well as equal expression of both alleles. Also at the protein level, allelic imbalance was determined. Most interestingly, we also discovered allelic imbalance and balance in non-HCM donors. Our findings therefore strongly indicate that apart from mutation-specific mechanisms, also non-HCM associated allelic-mRNA expression regulation may account for the allelic imbalance of the MYH7 gene in HCM-patients. Since the relative amount of mutant mRNA and protein or the extent of allelic imbalance has been associated with the severity of HCM, individual analysis of the MYH7-allelic expression may provide valuable information for the prognosis of each patient.

Molecular characterization of the new defective P(brescia) alpha1-antitrypsin allele.

PubMed

Medicina, Daniela; Montani, Nadia; Fra, Anna M; Tiberio, Laura; Corda, Luciano; Miranda, Elena; Pezzini, Alessandro; Bonetti, Fausta; Ingrassia, Rosaria; Scabini, Roberta; Facchetti, Fabio; Schiaffonati, Luisa

2009-08-01

Alpha1-antitrypsin (alpha(1)AT) deficiency is a hereditary disorder associated with reduced alpha(1)AT serum level, predisposing adults to pulmonary emphysema. Among the known mutations of the alpha(1)AT gene (SERPINA1) causing alpha(1)AT deficiency, a few alleles, particularly the Z allele, may also predispose adults to liver disease. We have characterized a new defective alpha(1)AT allele (c.745G>C) coding for a mutant alpha(1)AT (Gly225Arg), named P(brescia). The P(brescia) alpha(1)AT allele was first identified in combination with the rare defective M(würzburg) allele in an 11-year-old boy showing significantly reduced serum alpha(1)AT level. Subsequently, the P(brescia) allele was found in the heterozygous state with the normal M or the defective Z allele in nine and three adults respectively. In cellular models of the disease, we show that the P(brescia) mutant is retained in the endoplasmic reticulum as ordered polymers and is secreted more slowly than the normal M alpha(1)AT. This behaviour recapitulates the abnormal cellular handling and fate of the Z alpha(1)AT and suggests that the mutation present in the P(brescia) alpha(1)AT causes a conformational change of the protein which, by favouring polymer formation, is etiologic to both severe alpha(1)AT deficiency in the plasma and toxic protein-overload in the liver.

A new spontaneous allele at the pink-eyed dilution (p) locus discovered in Mus musculus castaneus.

PubMed

Tsuji, A; Wakayama, T; Ishikawa, A

1995-10-01

Mutant mice characterized by a cream coat and pink eyes were spontaneously discovered among the descendants of Indonesian wild mice (Mus musculus castaneus). This mutant phenotype was controlled by a single autosomal recessive gene that was allelic to the pink-eyed dilution (p) gene. The mutant mouse phenotypically resembled the original p mouse which was the first mutant identified at this locus. Nevertheless, these two alleles differed in origin, a previous report suggesting that the original p allele was derived from Japanese wild mice (M. m. molossinus). Thus the symbol pcas (pink-eyed castaneus) was proposed for the present mutation allele.

The relation of body mass index and abdominal adiposity with dyslipidemia in 27 general populations of the WHO MONICA Project.

PubMed

Wietlisbach, V; Marques-Vidal, P; Kuulasmaa, K; Karvanen, J; Paccaud, F

2013-05-01

The association between adiposity measures and dyslipidemia has seldom been assessed in a multipopulational setting. 27 populations from Europe, Australia, New Zealand and Canada (WHO MONICA project) using health surveys conducted between 1990 and 1997 in adults aged 35-64 years (n = 40,480). Dyslipidemia was defined as the total/HDL cholesterol ratio >6 (men) and >5 (women). Overall prevalence of dyslipidemia was 25% in men and 23% in women. Logistic regression showed that dyslipidemia was strongly associated with body mass index (BMI) in men and with waist circumference (WC) in women, after adjusting for region, age and smoking. Among normal-weight men and women (BMI<25 kg/m(2)), an increase in the odds for being dyslipidemic was observed between lowest and highest WC quartiles (OR = 3.6, p < 0.001). Among obese men (BMI ≥ 30), the corresponding increase was smaller (OR = 1.2, p = 0.036). A similar weakening was observed among women. Classification tree analysis was performed to assign subjects into classes of risk for dyslipidemia. BMI thresholds (25.4 and 29.2 kg/m(2)) in men and WC thresholds (81.7 and 92.6 cm) in women came out at first stages. High WC (>84.8 cm) in normal-weight men, menopause in women and regular smoking further defined subgroups at increased risk. standard categories of BMI and WC, or their combinations, do not lead to optimal risk stratification for dyslipidemia in middle-age adults. Sex-specific adaptations are necessary, in particular by taking into account abdominal obesity in normal-weight men, post-menopausal age in women and regular smoking in both sexes. Copyright © 2011 Elsevier B.V. All rights reserved.

Extensive variation between tissues in allele specific expression in an outbred mammal.

PubMed

Chamberlain, Amanda J; Vander Jagt, Christy J; Hayes, Benjamin J; Khansefid, Majid; Marett, Leah C; Millen, Catriona A; Nguyen, Thuy T T; Goddard, Michael E

2015-11-23

Allele specific gene expression (ASE), with the paternal allele more expressed than the maternal allele or vice versa, appears to be a common phenomenon in humans and mice. In other species the extent of ASE is unknown, and even in humans and mice there are several outstanding questions. These include; to what extent is ASE tissue specific? how often does the direction of allele expression imbalance reverse between tissues? how often is only one of the two alleles expressed? is there a genome wide bias towards expression of the paternal or maternal allele; and finally do genes that are nearby on a chromosome share the same direction of ASE? Here we use gene expression data (RNASeq) from 18 tissues from a single cow to investigate each of these questions in turn, and then validate some of these findings in two tissues from 20 cows. Between 40 and 100 million sequence reads were generated per tissue across three replicate samples for each of the eighteen tissues from the single cow (the discovery dataset). A bovine gene expression atlas was created (the first from RNASeq data), and differentially expressed genes in each tissue were identified. To analyse ASE, we had access to unambiguously phased genotypes for all heterozygous variants in the cow's whole genome sequence, where these variants were homozygous in the whole genome sequence of her sire, and as a result we were able to map reads to parental genomes, to determine SNP and genes showing ASE in each tissue. In total 25,251 heterozygous SNP within 7985 genes were tested for ASE in at least one tissue. ASE was pervasive, 89 % of genes tested had significant ASE in at least one tissue. This large proportion of genes displaying ASE was confirmed in the two tissues in a validation dataset. For individual tissues the proportion of genes showing significant ASE varied from as low as 8-16 % of those tested in thymus to as high as 71-82 % of those tested in lung. There were a number of cases where the direction of

Caloric sweetener consumption and dyslipidemia among US adults.

PubMed

Welsh, Jean A; Sharma, Andrea; Abramson, Jerome L; Vaccarino, Viola; Gillespie, Cathleen; Vos, Miriam B

2010-04-21

Dietary carbohydrates have been associated with dyslipidemia, a lipid profile known to increase cardiovascular disease risk. Added sugars (caloric sweeteners used as ingredients in processed or prepared foods) are an increasing and potentially modifiable component in the US diet. No known studies have examined the association between the consumption of added sugars and lipid measures. To assess the association between consumption of added sugars and blood lipid levels in US adults. Cross-sectional study among US adults (n = 6113) from the National Health and Nutrition Examination Survey (NHANES) 1999-2006. Respondents were grouped by intake of added sugars using limits specified in dietary recommendations (< 5% [reference group], 5%-<10%, 10%-<17.5%, 17.5%-<25%, and > or = 25% of total calories). Linear regression was used to estimate adjusted mean lipid levels. Logistic regression was used to determine adjusted odds ratios of dyslipidemia. Interactions between added sugars and sex were evaluated. Adjusted mean high-density lipoprotein cholesterol (HDL-C), geometric mean triglycerides, and mean low-density lipoprotein cholesterol (LDL-C) levels and adjusted odds ratios of dyslipidemia, including low HDL-C levels (< 40 mg/dL for men; < 50 mg/dL for women), high triglyceride levels (> or = 150 mg/dL), high LDL-C levels (> or = 130 mg/dL), or high ratio of triglycerides to HDL-C (> 3.8). Results were weighted to be representative of the US population. A mean of 15.8% of consumed calories was from added sugars. Among participants consuming less than 5%, 5% to less than 17.5%, 17.5% to less than 25%, and 25% or greater of total energy as added sugars, adjusted mean HDL-C levels were, respectively, 58.7, 57.5, 53.7, 51.0, and 47.7 mg/dL (P < .001 for linear trend), geometric mean triglyceride levels were 105, 102, 111, 113, and 114 mg/dL (P < .001 for linear trend), and LDL-C levels modified by sex were 116, 115, 118, 121, and 123 mg/dL among women (P = .047 for linear

Dyslipidemia in PCOS.

PubMed

Wild, Robert A

2012-03-10

Life-long apolipoprotein lipid metabolic dysfunction in women with PCOS exaggerates the risk for cardiovascular disease (CVD) with aging. The dysfunction has involved insulin resistance (IR), which occurs in most women with PCOS. Women with PCOS have androgen excess, IR, variable amounts of estrogen exposure, and many environmental factors, all of which can influence lipid metabolism. On average, women with PCOS were higher triglyceride [26.39 95% CI (17.24, 35.54)], lower HDL-cholesterol [6.41 95% CI (3.69, 9.14)], and higher non HDL cholesterol levels [18.82 95% CI (15.53, 22.11)] than their non-PCOS counterparts. They have higher ApoCIII/ApoCII ratios and higher ApoCI even if they are not obese. ApoC1 elevation in women with PCOS needs to be further evaluated as a marker of dysfunction and potential CVD risk. ApoB measurements track with non-HDL cholesterol as a surrogate for increased atherogenic circulating small LDL particles. Elevated triglycerides and waist circumference predict CVD risk and women with PCOS often have these phenotypes. Diet and exercise interventions followed by selective lipid lowering medications are encouraged to normalize the dyslipidemia. Copyright © 2012 Elsevier Inc. All rights reserved.

Fetal and infant exposure to severe Chinese famine increases the risk of adult dyslipidemia: Results from the China health and retirement longitudinal study.

PubMed

Wang, Zhenghe; Li, Changwei; Yang, Zhongping; Ma, Jun; Zou, Zhiyong

2017-06-14

To explore the associations between the Chinese famine exposure in early life and the dyslipidemia in adulthood. We selected 2752 participants from the baseline survey of China Health and Retirement Longitudinal Study (CHARLS) 2011-2012 to evaluate the associations of early life the Chinese famine exposure with risk of dyslipidemia in adulthood. Dyslipidemia was defined as TC (Total Cholesterol): HDL-C (High-Density Lipoprotein Cholesterol) ratio ≥ 5.0 or use cholesterol lowering drugs. Famine exposure cohorts were categorized by birthdates of participants. Binary logistics regression model was used to examine the associations of early-life famine exposure with the risk of dyslipidemia. The dyslipidemia prevalence of the non-exposed cohort, fetal stage-, infant stage-, and preschool stage-exposed cohorts in adulthood was 15.7%, 23.1%, 22.0%, and 18.6%, respectively. Early-life exposure to the Chinese famine significantly increased LDL cholesterol concentrations in adulthood after adjusted for age. The risks of dyslipidemia in fetal (OR = 1.58; 95% CI: 1.23-2.03; P < 0.001) and infant (OR = 1.52; 95% CI: 1.15-2.00; P = 0.003) stage-exposed cohorts were significantly higher than the non-exposed cohort after adjusted for gender and current family economic status. Following gender stratification, we found that fetal (OR = 1.80; 95% CI: 1.26-2.57; P = 0.001), infant (OR = 1.75; 95% CI: 1.17-2.62; P = 0.006), and preschool (OR = 1.63; 95% CI: 1.10-2.42; P = 0.015) -stage exposure to severe famine aggravated the risk of dyslipidemia in female adults. However, the similar association was not observed for male adults. Early-life exposure to severe Chinese famine could link with the higher dyslipidemia risk in female adulthood, but not in male adulthood. This gender-specific effect might be associated with the hypothesis that parents in China prefer boys to girls traditionally or survivors' bias.

Prevalence and treatment of atherogenic dyslipidemia in the primary prevention of cardiovascular disease in Europe: EURIKA, a cross-sectional observational study.

PubMed

Halcox, Julian P; Banegas, José R; Roy, Carine; Dallongeville, Jean; De Backer, Guy; Guallar, Eliseo; Perk, Joep; Hajage, David; Henriksson, Karin M; Borghi, Claudio

2017-06-17

Atherogenic dyslipidemia is associated with poor cardiovascular outcomes, yet markers of this condition are often ignored in clinical practice. Here, we address a clear evidence gap by assessing the prevalence and treatment of two markers of atherogenic dyslipidemia: elevated triglyceride levels and low levels of high-density lipoprotein cholesterol. This cross-sectional observational study assessed the prevalence of two atherogenic dyslipidemia markers, high triglyceride levels and low high-density lipoprotein cholesterol levels, in the study population from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA; N = 7641; of whom 51.6% were female and 95.6% were White/Caucasian). The EURIKA population included European patients, aged at least 50 years with at least one cardiovascular risk factor but no history of cardiovascular disease. Over 20% of patients from the EURIKA population have either triglyceride or high-density lipoprotein cholesterol levels characteristic of atherogenic dyslipidemia. Furthermore, the proportions of patients with one of these markers were higher in subpopulations with type 2 diabetes mellitus or those already calculated to be at high risk of cardiovascular disease. Approximately 55% of the EURIKA population who have markers of atherogenic dyslipidemia are not receiving lipid-lowering therapy. A considerable proportion of patients with at least one major cardiovascular risk factor in the primary cardiovascular disease prevention setting have markers of atherogenic dyslipidemia. The majority of these patients are not receiving optimal treatment, as specified in international guidelines, and thus their risk of developing cardiovascular disease is possibly underestimated. The present study is registered with ClinicalTrials.gov (ID: NCT00882336).

Adipocyte Triglyceride Turnover Is Independently Associated With Atherogenic Dyslipidemia

PubMed Central

Frayn, Keith; Bernard, Samuel; Spalding, Kirsty; Arner, Peter

2012-01-01

Background Inappropriate storage of fatty acids as triglycerides in adipocytes and their removal from adipocytes through lipolysis and subsequent oxidation may cause the atherogenic dyslipidemia phenotype of elevated apolipoprotein B levels and subsequent hypertriglyceridemia. We tested whether turnover of triglycerides in fat cells was related to dyslipidemia. Methods and Results The age of triglycerides (reflecting removal) and triglyceride storage in adipocytes was determined under free living conditions by measuring incorporation of atmospheric 14C into these lipids within the adipocytes in 47 women and 26 men with a large interindividual variability in body mass index. Because limited 14C data were available, triglyceride age was also determined in 97 men and 233 women by using an algorithm based on adipocyte lipolysis, body fat content, waist‐to‐hip ratio, and insulin sensitivity. This cohort consisted of nonobese subjects since obesity per se is related to all components in the algorithm. Triglyceride turnover (age and storage) was compared with plasma levels of apolipoproteins and lipids. Plasma levels of apolipoprotein B and triglycerides were positively related to triglyceride age in adipocytes, when measured directly using radiocarbon analyses (r=0.45 to 0.47; P<0.0001). This effect was independent of subject age, waist circumference measures, and insulin sensitivity (partial r=0.29 to 0.45; P from 0.03 to <0.0001). Triglyceride storage showed no independent correlation (partial r=0.02 to 0.11; P=0.42 to 0.91). Algorithm‐based values for adipocyte removal of triglycerides were positively associated with plasma triglycerides and apolipoprotein B (r=0.44 to 0.45; P<0.0001) and (also positively) with the inflammation status of adipose tissue (r=0.39 to 0.47; P<0.05). These correlations were statistically independent of subject age and observed in men and women as well as in lean and overweight subjects when subgroups were examined separately

Molecular identification of rare FY*Null and FY*X alleles in Caucasian thalassemic family from Sardinia.

PubMed

Manfroi, Silvia; Scarcello, Antonio; Pagliaro, Pasqualepaolo

2015-10-01

Molecular genetic studies on Duffy blood group antigens have identified mutations underlying rare FY*Null and FY*X alleles. FY*Null has a high frequency in Blacks, especially from sub-Saharan Africa, while its frequency is not defined in Caucasians. FY*X allele, associated with Fy(a-b+w) phenotype, has a frequency of 2-3.5% in Caucasian people while it is absent in Blacks. During the project of extensive blood group genotyping in patients affected by hemoglobinopathies, we identified FY*X/FY*Null and FY*A/FY*Null genotypes in a Caucasian thalassemic family from Sardinia. We speculate on the frequency of FY*X and FY*Null alleles in Caucasian and Black people; further, we focused on the association of FY*X allele with weak Fyb antigen expression on red blood cells and its identification performing high sensitivity serological typing methods or genotyping. Copyright © 2015 Elsevier Ltd. All rights reserved.

Allelic Variants of Complement Genes Associated with Dense Deposit Disease

PubMed Central

Abrera-Abeleda, Maria Asuncion; Nishimura, Carla; Frees, Kathy; Jones, Michael; Maga, Tara; Katz, Louis M.; Zhang, Yuzhou

2011-01-01

The alternative pathway of the complement cascade plays a role in the pathogenesis of dense deposit disease (DDD). Deficiency of complement factor H and mutations in CFH associate with the development of DDD, but it is unknown whether allelic variants in other complement genes also associate with this disease. We studied patients with DDD and identified previously unreported sequence alterations in several genes in addition to allelic variants and haplotypes common to patients with DDD. We found that the likelihood of developing DDD increases with the presence of two or more risk alleles in CFH and C3. To determine the functional consequence of this finding, we measured the activity of the alternative pathway in serum samples from phenotypically normal controls genotyped for variants in CFH and C3. Alternative pathway activity was higher in the presence of variants associated with DDD. Taken together, these data confirm that DDD is a complex genetic disease and may provide targets for the development of disease-specific therapies. PMID:21784901

Dyslipidemia alters sperm maturation and capacitation in LXR-null mice.

PubMed

Whitfield, M; Guiton, R; Rispal, J; Acar, N; Kocer, A; Drevet, J R; Saez, F

2017-12-01

Lipid metabolism disorders (dyslipidemia) are causes of male infertility, but little is known about their impact on male gametes when considering post-testicular maturation events, given that studies concentrate most often on endocrine dysfunctions and testicular consequences. In this study, three-month-old wild-type ( wt ) and Liver-X-Receptors knock out ( Lxrα;β - / - ) males were fed four weeks with a control or a lipid-enriched diet containing 1.25% cholesterol (high cholesterol diet (HCD)). The HCD triggered a dyslipidemia leading to sperm post-testicular alterations and infertility. Sperm lipids were analyzed by LC-MS and those from Lxrα;β - / - males fed the HCD showed higher chol/PL and PC/PE ratios compared to wt -HCD ( P  < 0.05) and lower oxysterol contents compared to wt ( P  < 0.05) or Lxrα;β - / - ( P  < 0.05). These modifications impaired membrane-associated events triggering the tyrosine phosphorylation normally occurring during the capacitation process, as shown by phosphotyrosine Western blots. Using flow cytometry, we showed that a smaller subpopulation of spermatozoa from Lxrα;β - / - -HCD males could raise their membrane fluidity during capacitation ( P  < 0.05 vs wt or wt-HCD ) as well as their intracellular calcium concentration ( P  < 0.05 vs Lxrα;β - / - and P  < 0.001 vs wt ). The accumulation of the major sperm calcium efflux pump (PMCA4) was decreased in Lxrα;β - / - males fed the HCD ( P  < 0.05 vs Lxrα;β - / - and P  < 0.001 vs wt ). This study is the first showing an impact of dyslipidemia on post-testicular sperm maturation with consequences on the capacitation signaling cascade. It may lead to the identification of fertility prognostic markers in this pathophysiological situation, which could help clinicians to better understand male infertilities which are thus far classified as idiopathic. © 2017 Society for Reproduction and Fertility.

Evolutionary dynamics of sporophytic self-incompatibility alleles in plants.

PubMed

Schierup, M H; Vekemans, X; Christiansen, F B

1997-10-01

The stationary frequency distribution and allelic dynamics in finite populations are analyzed through stochastic simulations in three models of single-locus, multi-allelic sporophytic self-incompatibility. The models differ in the dominance relationships among alleles. In one model, alleles act codominantly in both pollen and style (SSIcod), in the second, alleles form a dominance hierarchy in pollen and style (SSIdom). In the third model, alleles interact codominantly in the style and form a dominance hierarchy in the pollen (SSIdomcod). The SSIcod model behaves similarly to the model of gametophytic self-incompatibility, but the selection intensity is stronger. With dominance, dominant alleles invade the population more easily than recessive alleles and have a lower frequency at equilibrium. In the SSIdom model, recessive alleles have both a higher allele frequency and higher expected life span. In the SSIdomcod model, however, loss due to drift occurs more easily for pollen-recessive than for pollen-dominant alleles, and therefore, dominant alleles have a higher expected life span than the more recessive alleles. The process of allelic turnover in the SSIdomcod and SSIdom models is closely approximated by a random walk on a dominance ladder. Implications of the results for experimental studies of sporophytic self-incompatibility in natural populations are discussed.

Omega-3 carboxylic acids monotherapy and combination with statins in the management of dyslipidemia.

PubMed

Benes, Lane B; Bassi, Nikhil S; Davidson, Michael H

2016-01-01

The 2013 American College of Cardiology/American Heart Association guidelines on cholesterol management placed greater emphasis on statin therapy given the well-established benefits in primary and secondary prevention of cardiovascular disease. Residual risk may remain after statin initiation, in part because of triglyceride-rich lipoprotein cholesterol. Several large trials have failed to show benefit with non-statin cholesterol-lowering medications in the reduction of cardiovascular events. Yet, subgroup analyses showed a benefit in those with hypertriglyceridemia and lower high-density lipoprotein cholesterol level, a high-risk pattern of dyslipidemia. This review discusses the benefits of omega-3 carboxylic acids, a recently approved formulation of omega-3 fatty acid with enhanced bioavailability, in the treatment of dyslipidemia both as monotherapy and combination therapy with a statin.

[Study on rules of TCM syndrome in patients with dyslipidemia and its objectization].

PubMed

Lei, Yan; Wang, Zhen-Hua; Liu, Jian-Gang

2007-12-01

To explore the rules of TCM syndrome in patients with dyslipidemia and its relation with C-reactive protein (CRP), homocysteine (Hcy), carotid ultrasonic picture, blood lipids and blood viscosity. From 152 recruited patients symptoms and physical signs (including figures of tongue and pulse) were selected and analyzed in grading and quantifying by factor analysis. At the same time, blood lipids, CRP, Hcy, carotid ultrasonic picture and blood viscosity were detected to conduct a canonical correlation analysis for exploring the relationship between different TCM syndromes and their corresponding physical and/or chemical indexes. Five types of TCM syndrome obtained by factor analysis were syndrome of Shen-yin deficiency (I), Pi-qi deficiency (II), turbid-phlegm impediment (III), blood stasis (IV), and phlegm-blood block (V). By canonical correlation analysis, they were characterized with: Type I, high levels of CRP and blood viscosity; Type II, high level of very low-density lipoprotein cholesterol (VLDL-C); Type III, high level of total cholesterol (TC) and low level of high-density lipoprotein cholesterol (HDL-C); and Type V, high level of Hcy. The five syndrome types frequently found in patients with dyslipidemia are syndrome of Shen-yin deficiency, Pi-qi deficiency, turbid-phlegm impediment, blood stasis, and phlegm-blood block. Different syndrome has its own correlation with some corresponding physical and/or chemical laboratory indexes, the issue provides new evidences for the objectification of TCM syndromes in patients with dyslipidemia.

A common allele on chromosome 9 associated with coronary heartdisease

DOE Office of Scientific and Technical Information (OSTI.GOV)

McPherson, Ruth; Pertsemlidis, Alexander; Kavaslar, Nihan

2007-03-01

Coronary heart disease (CHD) is a major cause of death in Western countries. Here we used genome-wide association scanning to identify a 58 kb interval on chromosome 9 that was consistently associated with CHD in six independent samples. The interval contains no annotated genes and is not associated with established CHD risk factors such as plasma lipoproteins, hypertension or diabetes. Homozygotes for the risk allele comprise 20-25% of Caucasians and have a {approx}30-40% increased risk of CHD. These data indicate that the susceptibility allele acts through a novel mechanism to increase CHD risk in a large fraction of the population.

Genotyping of HLA-I and HLA-II alleles in Chinese patients with paraneoplastic pemphigus.

PubMed

Liu, Q; Bu, D-F; Li, D; Zhu, X-J

2008-03-01

Class I and class II HLA genes are thought to play a role in the immunopathogenesis of bullous dermatoses such as pemphigus vulgaris and pemphigus foliaceus, but we know little about the genetic background of paraneoplastic pemphigus (PNP) in Chinese patients. To identify class I and class II HLA alleles by genotyping in Chinese patients with PNP, and to find out the possible association between HLA alleles and disease susceptibility. Nineteen Chinese patients with PNP were enrolled in this study. HLA-A, B, C, DRB1 and DQB1 alleles were typed by polymerase chain reaction and a colour-coded sequence-specific oligonucleotide probes method. The frequencies of HLA-B*4002/B*4004, B*51, B*52, Cw*14, DQB1*0301, DRB1*08 and DRB1*11 were relatively prevalent in Chinese Han patients with PNP in comparison with normal controls. After correction for multiple comparisons, Cw*14 remained statistically significant, and the other alleles were unremarkable in these patients. The genetic background predisposing to PNP may be different in patients from various races and areas. HLA-Cw*14 may be the predisposing allele to PNP in Chinese patients, which is different from the predisposing allele in French patients with PNP and the alleles predisposing to pemphigus vulgaris and pemphigus foliaceus.

Management of Dyslipidemia in Type 2 Diabetes: Recent Advances in Nonstatin Treatment.

PubMed

Sugiyama, Kazutoshi; Saisho, Yoshifumi

2018-05-24

Dyslipidemia is a major risk factor for cardiovascular disease (CVD), which is the leading cause of morbidity and mortality in type 2 diabetes (T2DM). Statins have played a crucial role in its management, but residual risk remains since many patients cannot achieve their desired low-density lipoprotein cholesterol (LDL-C) level and up to 20% of patients are statin-intolerant, experiencing adverse events perceived to be caused by statins, most commonly muscle symptoms. Recently, great advances have been made in nonstatin treatment with ezetimibe, a cholesterol absorption inhibitor, and proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs), all showing a proven benefit with an excellent safety profile in cardiovascular outcome trials. This review summarizes the key aspects and the evolving role of these agents in the management of dyslipidemia in patients with T2DM, along with a brief introduction of novel drugs currently in development.

Therapeutic inertia in the outpatient management of dyslipidemia in patients with ischemic heart disease. The inertia study.

PubMed

Lázaro, Pablo; Murga, Nekane; Aguilar, Dolores; Hernández-Presa, Miguel A

2010-12-01

Studies indicate that dyslipidemia is undertreated. Numerous systematic reviews have shown that, even when therapeutic targets set by clinical practice guidelines have not been met, treatment remains unchanged despite the availability of alternatives approaches. The result is increased morbidity and mortality. Our aims were to investigate this phenomenon, known as therapeutic inertia, in patients with dyslipidemia and ischemic heart disease, and to determine its possible causes. national, multicenter, observational study of data obtained from physicians by questionnaire and from the clinical records of patients with ischemic heart disease. Main variable: therapeutic inertia during a consultation, defined as treatment remaining the same despite a change being indicated (e.g. low-density lipoprotein cholesterol >100 mg/dl or >70 mg/dl in diabetics). Covariates: physician, patient and consultation characteristics. multivariate logistic regression analysis of factors associated with therapeutic inertia during a consultation. Overall, 43% of consultations involved therapeutic inertia, and an association with coronary risk factors, including diabetes, did not result in a change in treatment. Therapeutic inertia occurred more frequently when there was a long time between the diagnosis and treatment of dyslipidemia and that of ischemic heart disease. Undertreatment was particularly common in women despite a greater overall risk. The more experienced physicians treated younger patients more appropriately. Clinical practice was improved by educational sessions at conferences. Therapeutic inertia was common in patients with chronic ischemic heart disease and dyslipidemia, irrespective of overall cardiovascular risk. Factors associated with the patient, disease and physician had an influence.

Bovine Polledness – An Autosomal Dominant Trait with Allelic Heterogeneity

PubMed Central

Medugorac, Ivica; Seichter, Doris; Graf, Alexander; Russ, Ingolf; Blum, Helmut; Göpel, Karl Heinrich; Rothammer, Sophie; Förster, Martin; Krebs, Stefan

2012-01-01

The persistent horns are an important trait of speciation for the family Bovidae with complex morphogenesis taking place briefly after birth. The polledness is highly favourable in modern cattle breeding systems but serious animal welfare issues urge for a solution in the production of hornless cattle other than dehorning. Although the dominant inhibition of horn morphogenesis was discovered more than 70 years ago, and the causative mutation was mapped almost 20 years ago, its molecular nature remained unknown. Here, we report allelic heterogeneity of the POLLED locus. First, we mapped the POLLED locus to a ∼381-kb interval in a multi-breed case-control design. Targeted re-sequencing of an enlarged candidate interval (547 kb) in 16 sires with known POLLED genotype did not detect a common allele associated with polled status. In eight sires of Alpine and Scottish origin (four polled versus four horned), we identified a single candidate mutation, a complex 202 bp insertion-deletion event that showed perfect association to the polled phenotype in various European cattle breeds, except Holstein-Friesian. The analysis of the same candidate interval in eight Holsteins identified five candidate variants which segregate as a 260 kb haplotype also perfectly associated with the POLLED gene without recombination or interference with the 202 bp insertion-deletion. We further identified bulls which are progeny tested as homozygous polled but bearing both, 202 bp insertion-deletion and Friesian haplotype. The distribution of genotypes of the two putative POLLED alleles in large semi-random sample (1,261 animals) supports the hypothesis of two independent mutations. PMID:22737241

Allele-specific gene expression in a wild nonhuman primate population

PubMed Central

Tung, J.; Akinyi, M. Y.; Mutura, S.; Altmann, J.; Wray, G. A.; Alberts, S. C.

2015-01-01

Natural populations hold enormous potential for evolutionary genetic studies, especially when phenotypic, genetic and environmental data are all available on the same individuals. However, untangling the genotype-phenotype relationship in natural populations remains a major challenge. Here, we describe results of an investigation of one class of phenotype, allele-specific gene expression (ASGE), in the well-studied natural population of baboons of the Amboseli basin, Kenya. ASGE measurements identify cases in which one allele of a gene is overexpressed relative to the alternative allele of the same gene, within individuals, thus providing a control for background genetic and environmental effects. Here, we characterize the incidence of ASGE in the Amboseli baboon population, focusing on the genetic and environmental contributions to ASGE in a set of eleven genes involved in immunity and defence. Within this set, we identify evidence for common ASGE in four genes. We also present examples of two relationships between cis-regulatory genetic variants and the ASGE phenotype. Finally, we identify one case in which this relationship is influenced by a novel gene-environment interaction. Specifically, the dominance rank of an individual’s mother during its early life (an aspect of that individual’s social environment) influences the expression of the gene CCL5 via an interaction with cis-regulatory genetic variation. These results illustrate how environmental and ecological data can be integrated into evolutionary genetic studies of functional variation in natural populations. They also highlight the potential importance of early life environmental variation in shaping the genetic architecture of complex traits in wild mammals. PMID:21226779

Geographical gradient of the eIF4E alleles conferring resistance to potyviruses in pea (Pisum) germplasm.

PubMed

Konečná, Eva; Šafářová, Dana; Navrátil, Milan; Hanáček, Pavel; Coyne, Clarice; Flavell, Andrew; Vishnyakova, Margarita; Ambrose, Mike; Redden, Robert; Smýkal, Petr

2014-01-01

The eukaryotic translation initiation factor 4E was shown to be involved in resistance against several potyviruses in plants, including pea. We combined our knowledge of pea germplasm diversity with that of the eIF4E gene to identify novel genetic diversity. Germplasm of 2803 pea accessions was screened for eIF4E intron 3 length polymorphism, resulting in the detection of four eIF4E(A-B-C-S) variants, whose distribution was geographically structured. The eIF4E(A) variant conferring resistance to the P1 PSbMV pathotype was found in 53 accessions (1.9%), of which 15 were landraces from India, Afghanistan, Nepal, and 7 were from Ethiopia. A newly discovered variant, eIF4E(B), was present in 328 accessions (11.7%) from Ethiopia (29%), Afghanistan (23%), India (20%), Israel (25%) and China (39%). The eIF4E(C) variant was detected in 91 accessions (3.2% of total) from India (20%), Afghanistan (33%), the Iberian Peninsula (22%) and the Balkans (9.3%). The eIF4E(S) variant for susceptibility predominated as the wild type. Sequencing of 73 samples, identified 34 alleles at the whole gene, 26 at cDNA and 19 protein variants, respectively. Fifteen alleles were virologically tested and 9 alleles (eIF4E(A-1-2-3-4-5-6-7), eIF4E(B-1), eIF4E(C-2)) conferred resistance to the P1 PSbMV pathotype. This work identified novel eIF4E alleles within geographically structured pea germplasm and indicated their independent evolution from the susceptible eIF4E(S1) allele. Despite high variation present in wild Pisum accessions, none of them possessed resistance alleles, supporting a hypothesis of distinct mode of evolution of resistance in wild as opposed to crop species. The Highlands of Central Asia, the northern regions of the Indian subcontinent, Eastern Africa and China were identified as important centers of pea diversity that correspond with the diversity of the pathogen. The series of alleles identified in this study provides the basis to study the co-evolution of potyviruses and the

Geographical Gradient of the eIF4E Alleles Conferring Resistance to Potyviruses in Pea (Pisum) Germplasm

PubMed Central

Konečná, Eva; Šafářová, Dana; Navrátil, Milan; Hanáček, Pavel; Coyne, Clarice; Flavell, Andrew; Vishnyakova, Margarita; Ambrose, Mike; Redden, Robert; Smýkal, Petr

2014-01-01

Background The eukaryotic translation initiation factor 4E was shown to be involved in resistance against several potyviruses in plants, including pea. We combined our knowledge of pea germplasm diversity with that of the eIF4E gene to identify novel genetic diversity. Methodology/Principal findings Germplasm of 2803 pea accessions was screened for eIF4E intron 3 length polymorphism, resulting in the detection of four eIF4EA-B-C-S variants, whose distribution was geographically structured. The eIF4EA variant conferring resistance to the P1 PSbMV pathotype was found in 53 accessions (1.9%), of which 15 were landraces from India, Afghanistan, Nepal, and 7 were from Ethiopia. A newly discovered variant, eIF4EB, was present in 328 accessions (11.7%) from Ethiopia (29%), Afghanistan (23%), India (20%), Israel (25%) and China (39%). The eIF4EC variant was detected in 91 accessions (3.2% of total) from India (20%), Afghanistan (33%), the Iberian Peninsula (22%) and the Balkans (9.3%). The eIF4ES variant for susceptibility predominated as the wild type. Sequencing of 73 samples, identified 34 alleles at the whole gene, 26 at cDNA and 19 protein variants, respectively. Fifteen alleles were virologically tested and 9 alleles (eIF4EA-1-2-3-4-5-6-7, eIF4EB-1, eIF4EC-2) conferred resistance to the P1 PSbMV pathotype. Conclusions/Significance This work identified novel eIF4E alleles within geographically structured pea germplasm and indicated their independent evolution from the susceptible eIF4ES1 allele. Despite high variation present in wild Pisum accessions, none of them possessed resistance alleles, supporting a hypothesis of distinct mode of evolution of resistance in wild as opposed to crop species. The Highlands of Central Asia, the northern regions of the Indian subcontinent, Eastern Africa and China were identified as important centers of pea diversity that correspond with the diversity of the pathogen. The series of alleles identified in this study provides the basis

Complex phenotype linked to a mutation in exon 11 of the lamin A/C gene: Hypertrophic cardiomyopathy, atrioventricular block, severe dyslipidemia and diabetes.

PubMed

Francisco, Ana Rita G; Santos Gonçalves, Inês; Veiga, Fátima; Mendes Pedro, Mónica; Pinto, Fausto J; Brito, Dulce

2017-09-01

The lamin A/C (LMNA) gene encodes lamins A and C, which have an important role in nuclear cohesion and chromatin organization. Mutations in this gene usually lead to the so-called laminopathies, the primary cardiac manifestations of which are dilated cardiomyopathy and intracardiac conduction defects. Some mutations, associated with lipodystrophy but not cardiomyopathy, have been linked to metabolic abnormalities such as diabetes and severe dyslipidemia. Herein we describe a new phenotype associated with a mutation in exon 11 of the LMNA gene: hypertrophic cardiomyopathy, atrioventricular block, severe dyslipidemia and diabetes. A 64-year-old woman with hypertrophic cardiomyopathy and a point mutation in exon 11 of the LMNA gene (c.1718C>T, Ser573Leu) presented with severe symptomatic ventricular hypertrophy and left ventricular outflow tract obstruction. She underwent septal alcohol ablation, followed by Morrow myectomy. The patient was also diagnosed with severe dyslipidemia, diabetes and obesity, and fulfilled diagnostic criteria for metabolic syndrome. No other characteristics of LMNA mutation-related phenotypes were identified. The development of type III atrioventricular block with no apparent cause, and mildly depressed systolic function, prompted referral for cardiac resynchronization therapy. In conclusion, the association between LMNA mutations and different phenotypes is complex and not fully understood, and can present with a broad spectrum of severity. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

HLA-DQA1/B1 alleles as putative susceptibility markers in congenital toxoplasmosis

PubMed Central

Shimokawa, Paulo Tadashi; Targa, Lília Spaleta; Yamamoto, Lidia; Rodrigues, Jonatas Cristian; Kanunfre, Kelly Aparecida; Okay, Thelma Suely

2016-01-01

ABSTRACT Host and parasite genotypes are among the factors associated with congenital toxoplasmosis pathogenesis. As HLA class II molecules play a key role in the immune system regulation, the aim of this study was to investigate whether HLA-DQA1/B1 alleles are associated with susceptibility or protection to congenital toxoplasmosis. One hundred and twenty-two fetuses with and 103 without toxoplasmosis were studied. The two study groups were comparable according to a number of socio-demographic and genetic variables. HLA alleles were typed by PCR-SSP. In the HLA-DQA1 region, the allele frequencies showed that *01:03 and *03:02 alleles could confer susceptibility (OR= 3.06, p = 0.0002 and OR= 9.60, p= 0.0001, respectively) as they were more frequent among infected fetuses. Regarding the HLA-DQB1 region, the *05:04 allele could confer susceptibility (OR = 6.95, p < 0.0001). Of the 122 infected fetuses, 10 presented susceptibility haplotypes contrasting with only one in the non-infected group. This difference was not statistically significant after correction for multiple comparison (OR = 9.37, p=0.011). In the casuistic, there were two severely damaged fetuses with high parasite loads determined in amniotic fluid samples and HLA-DQA1 susceptibility alleles. In the present study, a discriminatory potential of HLA-DQA1/B1 alleles to identify susceptibility to congenital toxoplasmosis and the most severe cases has been shown. PMID:26856406

Sequence-Based Genotyping of Expressed Swine Leukocyte Antigen Class I Alleles by Next-Generation Sequencing Reveal Novel Swine Leukocyte Antigen Class I Haplotypes and Alleles in Belgian, Danish, and Kenyan Fattening Pigs and Göttingen Minipigs.

PubMed

Sørensen, Maria Rathmann; Ilsøe, Mette; Strube, Mikael Lenz; Bishop, Richard; Erbs, Gitte; Hartmann, Sofie Bruun; Jungersen, Gregers

2017-01-01

The need for typing of the swine leukocyte antigen (SLA) is increasing with the expanded use of pigs as models for human diseases and organ-transplantation experiments, their use in infection studies, and for design of veterinary vaccines. Knowledge of SLA sequences is furthermore a prerequisite for the prediction of epitope binding in pigs. The low number of known SLA class I alleles and the limited knowledge of their prevalence in different pig breeds emphasizes the need for efficient SLA typing methods. This study utilizes an SLA class I-typing method based on next-generation sequencing of barcoded PCR amplicons. The amplicons were generated with universal primers and predicted to resolve 68-88% of all known SLA class I alleles dependent on amplicon size. We analyzed the SLA profiles of 72 pigs from four different pig populations; Göttingen minipigs and Belgian, Kenyan, and Danish fattening pigs. We identified 67 alleles, nine previously described haplotypes and 15 novel haplotypes. The highest variation in SLA class I profiles was observed in the Danish pigs and the lowest among the Göttingen minipig population, which also have the highest percentage of homozygote individuals. Highlighting the fact that there are still numerous unknown SLA class I alleles to be discovered, a total of 12 novel SLA class I alleles were identified. Overall, we present new information about known and novel alleles and haplotypes and their prevalence in the tested pig populations.

Etiology and management of dyslipidemia in children with chronic kidney disease and end-stage renal disease.

PubMed

Khurana, Mona; Silverstein, Douglas M

2015-12-01

Lipids are essential components of cell membranes, contributing to cell fuel, myelin formation, subcellular organelle function, and steroid hormone synthesis. Children with chronic kidney disease (CKD) and end-stage renal disease (ESRD) exhibit various co-morbidities, including dyslipidemia. The prevalence of dyslipidemias in children with CKD and ESRD is high, being present in 39-65% of patients. Elevated lipid levels in children without renal disease are a risk factor for cardiovascular disease (CVD), while the risk for CVD in pediatric CKD/ESRD is unclear. The pathogenesis of dyslipidemia in CKD features various factors, including increased levels of triglycerides, triglyceride-rich lipoproteins, apolipoprotein C3 (ApoC-III), decreased levels of cholesterylester transfer protein and high-density lipoproteins, and aberrations in serum very low-density and intermediate-density lipoproteins. If initial risk assessment indicates that a child with advanced CKD has 2 or more co-morbidities for CVD, first-line treatment should consist of non-pharmacologic management such as therapeutic lifestyle changes and dietary counseling. Pharmacologic treatment of dyslipidemia may reduce the incidence of CVD in children with CKD/ESRD, but randomized trials are lacking. Statins are the only class of lipid-lowering drugs currently approved by the U.S. Food and Drug Administration (FDA) for use in the pediatric population. FDA-approved pediatric labeling for these drugs is based on results from placebo-controlled trial results, showing 30-50% reductions in baseline low-density lipoprotein cholesterol. Although statins are generally well tolerated in adults, a spectrum of adverse events has been reported with their use in both the clinical trial and post-marketing settings.

A Meta-Analysis of Red Yeast Rice: An Effective and Relatively Safe Alternative Approach for Dyslipidemia

PubMed Central

Li, Yinhua; Jiang, Long; Jia, Zhangrong; Xin, Wei; Yang, Shiwei; Yang, Qiu; Wang, Luya

2014-01-01

Objective To explore whether red yeast rice is a safe and effective alternative approach for dyslipidemia. Methods Pubmed, the Cochrane Library, EBSCO host, Chinese VIP Information (VIP), China National Knowledge Infrastructure (CNKI), Wanfang Databases were searched for appropriate articles. Randomized trials of RYR (not including Xuezhikang and Zhibituo) and placebo as control in patients with dyslipidemia were considered. Two authors read all papers and independently extracted all relevant information. The primary outcomes were serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C). The secondary outcomes were increased levels of alanine transaminase, aspartate aminotransferase, creatine kinase, creatinine and fasting blood glucose. Results A total of 13 randomized, placebo-controlled trials containing 804 participants were analyzed. Red yeast rice exhibited significant lowering effects on serum TC [WMD = −0.97 (95% CI: −1.13, −0.80) mmol/L, P<0.001], TG [WMD = −0.23 (95% CI: −0.31, −0.14) mmol/L, P<0.001], and LDL-C [WMD = −0.87 (95% CI: −1.03, −0.71) mmol/L, P<0.001] but no significant increasing effect on HDL-C [WMD = 0.08 (95% CI: −0.02, 0.19) mmol/L, P = 0.11] compared with placebo. No serious side effects were reported in all trials. Conclusions The meta-analysis suggests that red yeast rice is an effective and relatively safe approach for dyslipidemia. However, further long-term, rigorously designed randomized controlled trials are still warranted before red yeast rice could be recommended to patients with dyslipidemia, especially as an alternative to statins. PMID:24897342

An allelic series at pax7a is associated with colour polymorphism diversity in Lake Malawi cichlid fish.

PubMed

Roberts, Reade B; Moore, Emily C; Kocher, Thomas D

2017-05-01

Despite long-standing interest in the evolution and maintenance of discrete phenotypic polymorphisms, the molecular genetic basis of such polymorphism in the wild is largely unknown. Female sex-associated blotched colour polymorphisms found in cichlids of Lake Malawi, East Africa, represent a highly successful polymorphic phenotype, found and maintained in four genera across the geographic expanse of the lake. Previously, we identified an association with an allelic variant of the paired-box transcription factor gene pax7a and blotched colour morphs in Lake Malawi cichlid fishes. Although a diverse range of blotched phenotypes are present in Lake Malawi cichlid species, they all appeared to result from an allele of pax7a that produces increased levels of transcript. Here, we examine the developmental and genetic basis of variation among blotched morphs. First, we confirm that pax7a-associated blotch morphs result primarily from modulation of melanophore development and survival. From laboratory crosses and natural population studies, we identify at least three alleles of pax7a associated with discrete subtypes of blotched morphs, in addition to the ancestral pax7a allele. Genotypes at pax7a support initial evolution of a novel pax7a allele to produce the blotched class of morphs, followed by subsequent evolution of that pax7a blotched allele to produce additional alleles associated with discrete colour morphs. Variant alleles of pax7a produce different levels of pax7a transcript, correlating with pigmentation phenotype at the cellular level. This naturally selected allelic series should serve as a case study for understanding the molecular genetic control of pax7a expression and the evolution of sex-associated alleles. © 2016 John Wiley & Sons Ltd.

Allelic genealogies in sporophytic self-incompatibility systems in plants.

PubMed

Schierup, M H; Vekemans, X; Christiansen, F B

1998-11-01

Expectations for the time scale and structure of allelic genealogies in finite populations are formed under three models of sporophytic self-incompatibility. The models differ in the dominance interactions among the alleles that determine the self-incompatibility phenotype: In the SSIcod model, alleles act codominantly in both pollen and style, in the SSIdom model, alleles form a dominance hierarchy, and in SSIdomcod, alleles are codominant in the style and show a dominance hierarchy in the pollen. Coalescence times of alleles rarely differ more than threefold from those under gametophytic self-incompatibility, and transspecific polymorphism is therefore expected to be equally common. The previously reported directional turnover process of alleles in the SSIdomcod model results in coalescence times lower and substitution rates higher than those in the other models. The SSIdom model assumes strong asymmetries in allelic action, and the most recessive extant allele is likely to be the most recent common ancestor. Despite these asymmetries, the expected shape of the allele genealogies does not deviate markedly from the shape of a neutral gene genealogy. The application of the results to sequence surveys of alleles, including interspecific comparisons, is discussed.

Phenotypic analysis of separation-of-function alleles of MEI-41, Drosophila ATM/ATR.

PubMed Central

Laurençon, Anne; Purdy, Amanda; Sekelsky, Jeff; Hawley, R Scott; Su, Tin Tin

2003-01-01

ATM/ATR kinases act as signal transducers in eukaryotic DNA damage and replication checkpoints. Mutations in ATM/ATR homologs have pleiotropic effects that range from sterility to increased killing by genotoxins in humans, mice, and Drosophila. Here we report the generation of a null allele of mei-41, Drosophila ATM/ATR homolog, and the use of it to document a semidominant effect on a larval mitotic checkpoint and methyl methanesulfonate (MMS) sensitivity. We also tested the role of mei-41 in a recently characterized checkpoint that delays metaphase/anaphase transition after DNA damage in cellular embryos. We then compare five existing mei-41 alleles to the null with respect to known phenotypes (female sterility, cell cycle checkpoints, and MMS resistance). We find that not all phenotypes are affected equally by each allele, i.e., the functions of MEI-41 in ensuring fertility, cell cycle regulation, and resistance to genotoxins are genetically separable. We propose that MEI-41 acts not in a single rigid signal transduction pathway, but in multiple molecular contexts to carry out its many functions. Sequence analysis identified mutations, which, for most alleles, fall in the poorly characterized region outside the kinase domain; this allowed us to tentatively identify additional functional domains of MEI-41 that could be subjected to future structure-function studies of this key molecule. PMID:12807779

High-resolution genetic mapping of allelic variants associated with cell wall chemistry in Populus

DOE PAGES

Muchero, Wellington; Guo, Jianjun; Difazio, Stephen P.; ...

2015-01-23

We report the identification of six genetic loci and the allelic-variants associated with Populus cell wall phenotypes determined independently using pyrolysis Molecular Beam Mass Spectrometry (pyMBMS), saccharification assay and wet chemistry in two partially overlapping populations of P. trichocarpa genotypes sampled from multiple environments in the Pacific Northwest of North America. All 6 variants co-located with a quantitative trait locus (QTL) hotspot on chromosome XIV for lignin content, syringyl to guaiacyl (S/G) ratio, 5- and 6- carbon sugars identified in an interspecific P. trichocarpa x P. deltoides pseudo-backcross mapping pedigree. Genomic intervals containing an amino acid transporter, a MYB transcriptionmore » factor, an angustifolia CtBP transcription factor, a copper transport protein ATOX1-related, a Ca 2+ transporting ATPase and a protein kinase were identified within 5 QTL regions. Each interval contained single nucleotide polymorphisms (SNPs) that were significantly associated to cell-wall phenotypes, with associations exceeding the chromosome-wise Bonferroni-adjusted p-values in at least one environment. cDNA sequencing for allelic variants of 3 of the 6 genes identified polymorphisms leading to premature stop codons in the MYB transcription factor and protein kinase. On the other hand, variants of the Angustifolia CtBP transcription factor exhibited a polyglutamine (PolyQ) length polymorphism. Results from transient protoplast assays suggested that each of the polymorphisms conferred allelic differences in activation of cellulose, hemicelluloses and lignin pathway marker genes, with truncated and short PolyQ alleles exhibiting significantly reduced marker gene activation. Genes identified in this study represent novel targets for reducing cell wall recalcitrance for lignocellulosic biofuels production using plant biomass.« less

The functional importance of sequence versus expression variability of MHC alleles in parasite resistance.

PubMed

Axtner, Jan; Sommer, Simone

2012-12-01

Understanding selection processes driving the pronounced allelic polymorphism of the major histocompatibility complex (MHC) genes and its functional associations to parasite load have been the focus of many recent wildlife studies. Two main selection scenarios are currently debated which explain the susceptibility or resistance to parasite infections either by the effects of (1) specific MHC alleles which are selected frequency-dependent in space and time or (2) a heterozygote or divergent allele advantage. So far, most studies have focused only on structural variance in co-evolutionary processes although this might not be the only trait subject to natural selection. In the present study, we analysed structural variance stretching from exon1 through exon3 of MHC class II DRB genes as well as genotypic expression variance in relation to the gastrointestinal helminth prevalence and infection intensity in wild yellow-necked mice (Apodemus flavicollis). We found support for the functional importance of specific alleles both on the sequence and expression level. By resampling a previously investigated study population we identified specific MHC alleles affected by temporal shifts in parasite pressure and recorded associated changes in allele frequencies. The allele Apfl-DRB*23 was associated with resistance to infections by the oxyurid nematode Syphacia stroma and at the same time with susceptibility to cestode infection intensity. In line with our expectation, MHC mRNA transcript levels tended to be higher in cestode-infected animals carrying the allele Apfl-DRB*23. However, no support for a heterozygote or divergent allele advantage on the sequence or expression level was detected. The individual amino acid distance of genotypes did not explain individual differences in parasite loads and the genetic distance had no effect on MHC genotype expression. For ongoing studies on the functional importance of expression variance in parasite resistance, allele

Allelic Variation of Bile Salt Hydrolase Genes in Lactobacillus salivarius Does Not Determine Bile Resistance Levels▿ †

PubMed Central

Fang, Fang; Li, Yin; Bumann, Mario; Raftis, Emma J.; Casey, Pat G.; Cooney, Jakki C.; Walsh, Martin A.; O'Toole, Paul W.

2009-01-01

Commensal lactobacilli frequently produce bile salt hydrolase (Bsh) enzymes whose roles in intestinal survival are unclear. Twenty-six Lactobacillus salivarius strains from different sources all harbored a bsh1 allele on their respective megaplasmids. This allele was related to the plasmid-borne bsh1 gene of the probiotic strain UCC118. A second locus (bsh2) was found in the chromosomes of two strains that had higher bile resistance levels. Four Bsh1-encoding allele groups were identified, defined by truncations or deletions involving a conserved residue. In vitro analyses showed that this allelic variation was correlated with widely varying bile deconjugation phenotypes. Despite very low activity of the UCC118 Bsh1 enzyme, a mutant lacking this protein had significantly lower bile resistance, both in vitro and during intestinal transit in mice. However, the overall bile resistance phenotype of this and other strains was independent of the bsh1 allele type. Analysis of the L. salivarius transcriptome upon exposure to bile and cholate identified a multiplicity of stress response proteins and putative efflux proteins that appear to broadly compensate for, or mask, the effects of allelic variation of bsh genes. Bsh enzymes with different bile-degrading kinetics, though apparently not the primary determinants of bile resistance in L. salivarius, may have additional biological importance because of varying effects upon bile as a signaling molecule in the host. PMID:19592587

Pharmacogenomics of sterol synthesis and statin use in schizophrenia subjects treated with antipsychotics.

PubMed

Vassas, Thomas J; Burghardt, Kyle J; Ellingrod, Vicki L

2014-01-01

Patients with schizophrenia treated with antipsychotics often develop metabolic side effects including dyslipidemia. Antipsychotics potentially upregulate gene expression of a lipid metabolism pathway protein called SREBP via SREB transcription factors (SREBFs). Genetic variation within SREBF may contribute to dyslipidemias and lipid medication efficacy within schizophrenia. A cross-sectional study of 157 patients were genotyped for SREBF1 (rs11868035) and SREBF2 (rs1057217) variants, and assessed for fasting lipids. The cohort's mean age was 46.6 years, was 64% male and 86% were using atypical antipsychotics. When stratified by statin use, those receiving a statin and carrying the SREBF1 T allele exhibited higher total cholesterol levels (p = 0.01), triglyceride levels (p = 0.04) and low-density lipoprotein levels (p = 0.03). A regression analysis controlling for gender differences in lipids showed that the SREBF1 T allele and statin interaction remained only for total cholesterol levels (F[4,149] = 5.8; p < 0.0001). For schizophrenia individuals with the SREBF1 rs11868035 T allele, incomplete response to statin medications may be seen. Future investigations may allow for personalizing dyslipidemia treatment based on pharmacogenetics within schizophrenia.

Platelet larger cell ratio (P-LCR) in patients with dyslipidemia.

PubMed

Grotto, H Z W; Noronha, J F A

2004-10-01

We have described preliminary results of platelet larger cell ratio (P-LCR) analysis, provided by an automated hematology analyzer in patients with hypercholesterolemia and/or hypertriglyceremia. P-LCR values were significantly higher in patients (n = 41) than in control normal group (n = 20) (P < 0.0001). Larger platelets are more reactive and contribute to vasooclusive events in patients with dyslipidemia. P-LCR may be used as an indicator of risk factor for thromboembolic ischemic events.

Geographically Distinct and Domain-Specific Sequence Variations in the Alleles of Rice Blast Resistance Gene Pib

PubMed Central

Vasudevan, Kumar; Vera Cruz, Casiana M.; Gruissem, Wilhelm; Bhullar, Navreet K.

2016-01-01

Rice blast is caused by Magnaporthe oryzae, which is the most destructive fungal pathogen affecting rice growing regions worldwide. The rice blast resistance gene Pib confers broad-spectrum resistance against Southeast Asian M. oryzae races. We investigated the allelic diversity of Pib in rice germplasm originating from 12 major rice growing countries. Twenty-five new Pib alleles were identified that have unique single nucleotide polymorphisms (SNPs), insertions and/or deletions, in addition to the polymorphic nucleotides that are shared between the different alleles. These partially or completely shared polymorphic nucleotides indicate frequent sequence exchange events between the Pib alleles. In some of the new Pib alleles, nucleotide diversity is high in the LRR domain, whereas, in others it is distributed among the NB-ARC and LRR domains. Most of the polymorphic amino acids in LRR and NB-ARC2 domains are predicted as solvent-exposed. Several of the alleles and the unique SNPs are country specific, suggesting a diversifying selection of alleles in various geographical locations in response to the locally prevalent M. oryzae population. Together, the new Pib alleles are an important genetic resource for rice blast resistance breeding programs and provide new information on rice-M. oryzae interactions at the molecular level. PMID:27446145

Allele-Specific Chromatin Recruitment and Therapeutic Vulnerabilities of ESR1 Activating Mutations.

PubMed

Jeselsohn, Rinath; Bergholz, Johann S; Pun, Matthew; Cornwell, MacIntosh; Liu, Weihan; Nardone, Agostina; Xiao, Tengfei; Li, Wei; Qiu, Xintao; Buchwalter, Gilles; Feiglin, Ariel; Abell-Hart, Kayley; Fei, Teng; Rao, Prakash; Long, Henry; Kwiatkowski, Nicholas; Zhang, Tinghu; Gray, Nathanael; Melchers, Diane; Houtman, Rene; Liu, X Shirley; Cohen, Ofir; Wagle, Nikhil; Winer, Eric P; Zhao, Jean; Brown, Myles

2018-02-12

Estrogen receptor α (ER) ligand-binding domain (LBD) mutations are found in a substantial number of endocrine treatment-resistant metastatic ER-positive (ER + ) breast cancers. We investigated the chromatin recruitment, transcriptional network, and genetic vulnerabilities in breast cancer models harboring the clinically relevant ER mutations. These mutants exhibit both ligand-independent functions that mimic estradiol-bound wild-type ER as well as allele-specific neomorphic properties that promote a pro-metastatic phenotype. Analysis of the genome-wide ER binding sites identified mutant ER unique recruitment mediating the allele-specific transcriptional program. Genetic screens identified genes that are essential for the ligand-independent growth driven by the mutants. These studies provide insights into the mechanism of endocrine therapy resistance engendered by ER mutations and potential therapeutic targets. Copyright © 2018 Elsevier Inc. All rights reserved.

Blood lipid profiles and factors associated with dyslipidemia assessed by a point-of-care testing device in an outpatient setting: A large-scale cross-sectional study in Southern China.

PubMed

Zhang, Pei-dong; He, Lin-yun; Guo, Yang; Liu, Peng; Li, Gong-xin; Wang, Li-zi; Liu, Ying-feng

2015-06-01

To promote the concept of POCT and to investigate dyslipidemia in Guangzhou, China, we performed a study examining blood lipids assessed by POCT and reported factors associated with dyslipidemia. This multicenter, cross-sectional study enrolled outpatients from 9 Guangzhou hospitals from May through September 2013. After informed consent was obtained, the following information was collected: age; gender; the presence of diabetes mellitus, obesity, and hypertension as well as current use of cigarettes or alcohol. Patients were asked to fast for 8h before the blood examination performed on a POCT device, the CardioChek PA. Of 4012 patients enrolled (1544 males, 2468 females; mean age 60.35±9.41 years), 1993 (49.7%) patients had dyslipidemia, but only 101 (5.1%) took statins. The multivariate tests of associations between demographic variables, comorbidities, and the risk of having dyslipidemia found that the significant predictors of dyslipidemia were male gender, age ≥60 years, being a current smoker or alcohol drinker, and hypertension. Most dyslipidemia patients in Guangzhou remain untreated. POCT in China is feasible, and its widespread use might improve dyslipidemia awareness, treatment and control. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Mutation intolerant genes and targets of FMRP are enriched for nonsynonymous alleles in schizophrenia.

PubMed

Leonenko, Ganna; Richards, Alexander L; Walters, James T; Pocklington, Andrew; Chambert, Kimberly; Al Eissa, Mariam M; Sharp, Sally I; O'Brien, Niamh L; Curtis, David; Bass, Nicholas J; McQuillin, Andrew; Hultman, Christina; Moran, Jennifer L; McCarroll, Steven A; Sklar, Pamela; Neale, Benjamin M; Holmans, Peter A; Owen, Michael J; Sullivan, Patrick F; O'Donovan, Michael C

2017-10-01

Risk of schizophrenia is conferred by alleles occurring across the full spectrum of frequencies from common SNPs of weak effect through to ultra rare alleles, some of which may be moderately to highly penetrant. Previous studies have suggested that some of the risk of schizophrenia is attributable to uncommon alleles represented on Illumina exome arrays. Here, we present the largest study of exomic variation in schizophrenia to date, using samples from the United Kingdom and Sweden (10,011 schizophrenia cases and 13,791 controls). Single variants, genes, and gene sets were analyzed for association with schizophrenia. No single variant or gene reached genome-wide significance. Among candidate gene sets, we found significant enrichment for rare alleles (minor allele frequency [MAF] < 0.001) in genes intolerant of loss-of-function (LoF) variation and in genes whose messenger RNAs bind to fragile X mental retardation protein (FMRP). We further delineate the genetic architecture of schizophrenia by excluding a role for uncommon exomic variants (0.01 ≤ MAF ≥ 0.001) that confer a relatively large effect (odds ratio [OR] > 4). We also show risk alleles within this frequency range exist, but confer smaller effects and should be identified by larger studies. © 2017 Wiley Periodicals, Inc.

Loss of microRNA-22 prevents high-fat diet induced dyslipidemia and increases energy expenditure without affecting cardiac hypertrophy.

PubMed

Diniz, Gabriela Placoná; Huang, Zhan-Peng; Liu, Jianming; Chen, Jinghai; Ding, Jian; Fonseca, Renata Inzinna; Barreto-Chaves, Maria Luiza; Donato, Jose; Hu, Xiaoyun; Wang, Da-Zhi

2017-12-15

Obesity is associated with development of diverse diseases, including cardiovascular diseases and dyslipidemia. MiRNA-22 (miR-22) is a critical regulator of cardiac function and targets genes involved in metabolic processes. Previously, we generated miR-22 null mice and we showed that loss of miR-22 blunted cardiac hypertrophy induced by mechanohormornal stress. In the present study, we examined the role of miR-22 in the cardiac and metabolic alterations promoted by high-fat (HF) diet. We found that loss of miR-22 attenuated the gain of fat mass and prevented dyslipidemia induced by HF diet, although the body weight gain, or glucose intolerance and insulin resistance did not seem to be affected. Mechanistically, loss of miR-22 attenuated the increased expression of genes involved in lipogenesis and inflammation mediated by HF diet. Similarly, we found that miR-22 mediates metabolic alterations and inflammation induced by obesity in the liver. However, loss of miR-22 did not appear to alter HF diet induced cardiac hypertrophy or fibrosis in the heart. Our study therefore establishes miR-22 as an important regulator of dyslipidemia and suggests it may serve as a potential candidate in the treatment of dyslipidemia associated with obesity. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project.

PubMed

Cross, Deanna S; Ivacic, Lynn C; Stefanski, Elisha L; McCarty, Catherine A

2010-06-17

There is a lack of knowledge regarding the frequency of disease associated polymorphisms in populations and population attributable risk for many populations remains unknown. Factors that could affect the association of the allele with disease, either positively or negatively, such as race, ethnicity, and gender, may not be possible to determine without population based allele frequencies.Here we used a panel of 51 polymorphisms previously associated with at least one disease and determined the allele frequencies within the entire Personalized Medicine Research Project population based cohort. We compared these allele frequencies to those in dbSNP and other data sources stratified by race. Differences in allele frequencies between self reported race, region of origin, and sex were determined. There were 19544 individuals who self reported a single racial category, 19027 or (97.4%) self reported white Caucasian, and 11205 (57.3%) individuals were female. Of the 11,208 (57%) individuals with an identifiable region of origin 8337 or (74.4%) were German.41 polymorphisms were significantly different between self reported race at the 0.05 level. Stratification of our Caucasian population by self reported region of origin revealed 19 polymorphisms that were significantly different (p = 0.05) between individuals of different origins. Further stratification of the population by gender revealed few significant differences in allele frequencies between the genders. This represents one of the largest population based allele frequency studies to date. Stratification by self reported race and region of origin revealed wide differences in allele frequencies not only by race but also by region of origin within a single racial group. We report allele frequencies for our Asian/Hmong and American Indian populations; these two minority groups are not typically selected for population allele frequency detection. Population wide allele frequencies are important for the design and

An overview of the new frontiers in the treatment of atherogenic dyslipidemias.

PubMed

Rached, F H; Chapman, M J; Kontush, A

2014-07-01

Cardiovascular diseases (CVDs) are the leading cause of morbidity/mortality worldwide. Dyslipidemia is a major risk factor for premature atherosclerosis and CVD. Lowering low-density-lipoprotein cholesterol (LDL-C) levels is well established as an intervention for the reduction of CVDs. Statins are the first-line drugs for treatment of dyslipidemia, but they do not address all CVD risk. Development of novel therapies is ongoing and includes the following: (i) reduction of LDL-C concentrations using antibodies to proprotein convertase subtilisin/kexin-9, antisense oligonucleotide inhibitors of apolipoprotein B production, microsomal transfer protein (MTP) inhibitors, and acyl-coenzyme A cholesterol acyl transferase inhibitors; (ii) reduction in levels of triglyceride-rich lipoproteins with ω-3 fatty acids, MTP inhibitors, and diacylglycerol acyl transferase-1 inhibitors; and (iii) increase of high-density-lipoprotein (HDL) cholesterol levels, HDL particle numbers, and/or HDL functionality using cholesteryl ester transfer protein inhibitors, HDL-derived agents, apolipoprotein AI mimetic peptides, and microRNAs. Large prospective outcome trials of several of these emerging therapies are under way, and thrilling progress in the field of lipid management is anticipated.

Visceral fat area is a strong predictor of leukocyte cell-derived chemotaxin 2, a potential biomarker of dyslipidemia.

PubMed

Tanisawa, Kumpei; Taniguchi, Hirokazu; Sun, Xiaomin; Ito, Tomoko; Kawakami, Ryoko; Sakamoto, Shizuo; Higuchi, Mitsuru

2017-01-01

Leukocyte cell-derived chemotaxin 2 (LECT2) is a hepatokine linking obesity to skeletal muscle insulin resistance. Although previous studies reported that obesity was associated with high levels of circulating LECT2 in human, the associations of detailed body fat distribution with LECT2 levels have not been examined. Furthermore, although animal study suggested that exercise decreased circulating LECT2 levels, it remains unknown whether physical fitness is associated with LECT2 levels in human. We therefore examined the relationship of plasma LECT2 levels with various adiposity indices and cardiorespiratory fitness (CRF) in middle-aged and elderly Japanese men. Furthermore, we examined the relationship of LECT2 levels with the presence of metabolic syndrome, hypertension, insulin resistance and dyslipidemia to determine the clinical significance of measuring circulating LECT2. This was a cross-sectional study of 143 Japanese men (age: 30-79 years). Participants' plasma LECT2 levels were measured by an enzyme-linked immunosorbent assay. To assess their abdominal fat distributions, visceral fat area (VFA) and subcutaneous fat area (SFA) were measured using magnetic resonance imaging. CRF was assessed by measuring peak oxygen uptake ([Formula: see text]). All adiposity indices measured in this study were positively correlated with plasma LECT2 levels, while [Formula: see text] was negatively correlated with LECT2 levels after adjustment for age. The correlations, except for VFA were no longer significant with further adjustment for VFA. Stepwise multiple linear regression analysis revealed that VFA was the strongest predictor of plasma LECT2 levels. Plasma LECT2 levels differed based on the presence of metabolic syndrome and dyslipidemia, but not hypertension and insulin resistance. Logistic regression analyses revealed that plasma LECT2 levels were significantly associated with dyslipidemia independently of VFA; VFA was not significantly associated with dyslipidemia

Dyslipidemia and Food Security in Low-Income US Adolescents: National Health and Nutrition Examination Survey, 2003–2010

PubMed Central

Laraia, Barbara A.; Leung, Cindy W.; Mietus-Snyder, Michele L.

2016-01-01

Introduction Low levels of food security are associated with dyslipidemia and chronic disease in adults, particularly in women. There is a gap in knowledge about the relationship between food security among youth and dyslipidemia and chronic disease. We investigated the relationship between food security status and dyslipidemia among low-income adolescents. Methods We analyzed data from adolescents aged 12 to 18 years (N = 1,072) from households with incomes at or below 200% of the federal poverty level from the National Health and Nutrition Examination Survey (NHANES) 2003–2010. We used logistic regression to examine the relationship between household food security status and the odds of having abnormalities with fasting total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), serum triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), TG/HDL-C ratio, and apolipoprotein B (Apo B). Models included age, sex, race/ethnicity, smoking status, partnered status in the household, and maternal education, with additional adjustment for adiposity. Results Household food security status was not associated with elevated TC or LDL-C. Adolescents with marginal food security were more likely than food-secure peers to have elevated TGs (odds ratio [OR] = 1.86; 95% confidence interval [CI], 1.14–3.05), TG/HDL-C ratio (OR = 1.74; 95% CI, 1.11–2.82), and Apo B (OR = 1.98; 95% CI, 1.17–3.36). Female adolescents with marginal food security had greater odds than male adolescents of having low HDL-C (OR = 2.69; 95% CI, 1.14–6.37). No elevated odds of dyslipidemia were found for adolescents with low or very low food security. Adjustment for adiposity did not attenuate estimates. Conclusion In this nationally representative sample, low-income adolescents living in households with marginal food security had increased odds of having a pattern consistent with atherogenic dyslipidemia, which represents a cardiometabolic burden above their risk from adiposity

Impact of Nutrients and Food Components on Dyslipidemias: What Is the Evidence?12

PubMed Central

Rosa, Carla de Oliveira Barbosa; dos Santos, Carolina Araújo; Leite, Jacqueline Isaura Alvarez; Caldas, Ana Paula Silva; Bressan, Josefina

2015-01-01

Dyslipidemias have been shown to bear a close association with an increased risk of cardiovascular diseases, atherosclerosis in particular. As efforts are being made to find alternative therapies and ways to prevent disease, there is a corresponding rise in public interest in food and/or active food components that contribute to an improved lipid profile and, thus, to better health. Besides supplying the basic nutrients necessary for well-being, some foods add further physiologic benefits. In fact, specific foods and bioactive components could be beneficial in controlling dyslipidemias. From a review of the literature on foods and bioactive compounds, their recommended quantities, and expected effects, we found that the following nutrients and food components could positively impact the lipid profile: monounsaturated and polyunsaturated fatty acids, soluble fiber, vegetable proteins, phytosterols, and polyphenols. Therefore, incorporating these components into the regular diets of individuals is justified, because they contribute additional positive effects. This suggests that they also be recommended in clinical practice. PMID:26567195

Urbanization, mainly rurality, but not altitude is associated with dyslipidemia profiles.

PubMed

Lazo-Porras, Maria; Bernabe-Ortiz, Antonio; Quispe, Renato; Málaga, German; Smeeth, Liam; Gilman, Robert H; Checkley, William; Miranda, J Jaime

Geographical and environmental features such as urbanization and altitude may influence individual's lipid profiles because of the diversity of human-environment interactions including lifestyles. To characterize the association between altitude and urbanization and lipid profile among Peruvian adults aged ≥35 years. Cross-sectional analysis of the CRONICAS Cohort Study. The outcomes of interest were 6 dyslipidemia traits: hypertriglyceridemia, high low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol (HDL-c), nonisolated low HDL-c, isolated low HDL-c, and high non-HDL-c. The exposures of interest were urbanization level (highly urban, urban, semi-urban, and rural) and altitude (high altitude vs sea level). Prevalence ratios (PRs) and 95% confidence intervals (95% CIs) were calculated using Poisson regression models with robust variance adjusting for potential confounders. Data from 3037 individuals, 48.5% males, mean age of 55.6 (standard deviation ±12.7) years, were analyzed. The most common dyslipidemia pattern was high non-HDL-c with a prevalence of 88.0% (95% CI: 84.9%-90.7%) in the rural area and 96.0% (95% CI: 94.5%-97.1%) in the semi-urban area. Relative to the highly urban area, living in rural areas was associated with a lower prevalence of hypertriglyceridemia (PR = 0.75; 95% CI: 0.56-0.99) and high non-HDL-c (PR = 0.96; 95% CI: 0.93-0.99), whereas living in semi-urban areas was associated with higher prevalence high low-density lipoprotein cholesterol (PR = 1.37; 95% CI: 1.11-1.67). Compared with sea level areas, high-altitude areas had lower prevalence of high non-HDL-c (PR = 0.97; 95% CI: 0.95-0.99). Urbanization but not altitude was associated to several dyslipidemia traits, with the exception of high non-HDL-c in high altitude settings. Copyright © 2017 National Lipid Association. All rights reserved.

QuASAR-MPRA: accurate allele-specific analysis for massively parallel reporter assays.

PubMed

Kalita, Cynthia A; Moyerbrailean, Gregory A; Brown, Christopher; Wen, Xiaoquan; Luca, Francesca; Pique-Regi, Roger

2018-03-01

The majority of the human genome is composed of non-coding regions containing regulatory elements such as enhancers, which are crucial for controlling gene expression. Many variants associated with complex traits are in these regions, and may disrupt gene regulatory sequences. Consequently, it is important to not only identify true enhancers but also to test if a variant within an enhancer affects gene regulation. Recently, allele-specific analysis in high-throughput reporter assays, such as massively parallel reporter assays (MPRAs), have been used to functionally validate non-coding variants. However, we are still missing high-quality and robust data analysis tools for these datasets. We have further developed our method for allele-specific analysis QuASAR (quantitative allele-specific analysis of reads) to analyze allele-specific signals in barcoded read counts data from MPRA. Using this approach, we can take into account the uncertainty on the original plasmid proportions, over-dispersion, and sequencing errors. The provided allelic skew estimate and its standard error also simplifies meta-analysis of replicate experiments. Additionally, we show that a beta-binomial distribution better models the variability present in the allelic imbalance of these synthetic reporters and results in a test that is statistically well calibrated under the null. Applying this approach to the MPRA data, we found 602 SNPs with significant (false discovery rate 10%) allele-specific regulatory function in LCLs. We also show that we can combine MPRA with QuASAR estimates to validate existing experimental and computational annotations of regulatory variants. Our study shows that with appropriate data analysis tools, we can improve the power to detect allelic effects in high-throughput reporter assays. http://github.com/piquelab/QuASAR/tree/master/mpra. fluca@wayne.edu or rpique@wayne.edu. Supplementary data are available online at Bioinformatics. © The Author (2017). Published by

Mining the human phenome using allelic scores that index biological intermediates.

PubMed

Evans, David M; Brion, Marie Jo A; Paternoster, Lavinia; Kemp, John P; McMahon, George; Munafò, Marcus; Whitfield, John B; Medland, Sarah E; Montgomery, Grant W; Timpson, Nicholas J; St Pourcain, Beate; Lawlor, Debbie A; Martin, Nicholas G; Dehghan, Abbas; Hirschhorn, Joel; Smith, George Davey

2013-10-01

It is common practice in genome-wide association studies (GWAS) to focus on the relationship between disease risk and genetic variants one marker at a time. When relevant genes are identified it is often possible to implicate biological intermediates and pathways likely to be involved in disease aetiology. However, single genetic variants typically explain small amounts of disease risk. Our idea is to construct allelic scores that explain greater proportions of the variance in biological intermediates, and subsequently use these scores to data mine GWAS. To investigate the approach's properties, we indexed three biological intermediates where the results of large GWAS meta-analyses were available: body mass index, C-reactive protein and low density lipoprotein levels. We generated allelic scores in the Avon Longitudinal Study of Parents and Children, and in publicly available data from the first Wellcome Trust Case Control Consortium. We compared the explanatory ability of allelic scores in terms of their capacity to proxy for the intermediate of interest, and the extent to which they associated with disease. We found that allelic scores derived from known variants and allelic scores derived from hundreds of thousands of genetic markers explained significant portions of the variance in biological intermediates of interest, and many of these scores showed expected correlations with disease. Genome-wide allelic scores however tended to lack specificity suggesting that they should be used with caution and perhaps only to proxy biological intermediates for which there are no known individual variants. Power calculations confirm the feasibility of extending our strategy to the analysis of tens of thousands of molecular phenotypes in large genome-wide meta-analyses. We conclude that our method represents a simple way in which potentially tens of thousands of molecular phenotypes could be screened for causal relationships with disease without having to expensively measure

Highly Purified Eicosapentaenoic Acid Increases Interleukin-10 Levels of Peripheral Blood Monocytes in Obese Patients With Dyslipidemia

PubMed Central

Satoh-Asahara, Noriko; Shimatsu, Akira; Sasaki, Yousuke; Nakaoka, Hidenori; Himeno, Akihiro; Tochiya, Mayu; Kono, Shigeo; Takaya, Tomohide; Ono, Koh; Wada, Hiromichi; Suganami, Takayoshi; Hasegawa, Koji; Ogawa, Yoshihiro

2012-01-01

OBJECTIVE It has recently been highlighted that proinflammatory (M1) macrophages predominate over anti-inflammatory (M2) macrophages in obesity, thereby contributing to obesity-induced adipose inflammation and insulin resistance. A recent clinical trial revealed that highly purified eicosapentaenoic acid (EPA) reduces the incidence of major coronary events. In this study, we examined the effect of EPA on M1/M2-like phenotypes of peripheral blood monocytes in obese dyslipidemic patients. RESEARCH DESIGN AND METHODS Peripheral blood monocytes were prepared from 26 obese patients without and 90 obese patients with dyslipidemia. Of the latter 90 obese patients with dyslipidemia, 82 patients were treated with or without EPA treatment (1.8 g daily) for 3 months. RESULTS Monocytes in obese patients with dyslipidemia showed a significantly lower expression of interleukin-10 (IL-10), an M2 marker, than those without dyslipidemia. EPA significantly increased serum IL-10 and EPA levels, the EPA/arachidonic acid (AA) ratio, and monocyte IL-10 expression and decreased the pulse wave velocity (PWV), an index of arterial stiffness, compared with the control group. After EPA treatment, the serum EPA/AA ratio was significantly correlated with monocyte IL-10 expression. Only increases in monocyte IL-10 expression and serum adiponectin were independent determinants of a decreased PWV by EPA. Furthermore, EPA significantly increased the expression and secretion of IL-10 in human monocytic THP-1 cells through a peroxisome proliferator–activated receptor (PPAR)γ-dependent pathway. CONCLUSIONS This study is the first to show that EPA increases the monocyte IL-10 expression in parallel with decrease of arterial stiffness, which may contribute to the antiatherogenic effect of EPA in obese dyslipidemic patients. PMID:22912426

CEF1/CDC5 alleles modulate transitions between catalytic conformations of the spliceosome

PubMed Central

Query, Charles C.; Konarska, Maria M.

2012-01-01

Conformational change within the spliceosome is required between the first and second catalytic steps of pre-mRNA splicing. A prior genetic screen for suppressors of an intron mutant that stalls between the two steps yielded both prp8 and non-prp8 alleles that suppressed second-step splicing defects. We have now identified the strongest non-prp8 suppressors as alleles of the NTC (Prp19 complex) component, CEF1. These cef1 alleles generally suppress second-step defects caused by a variety of intron mutations, mutations in U6 snRNA, or deletion of the second-step protein factor Prp17, and they can activate alternative 3′ splice sites. Genetic and functional interactions between cef1 and prp8 alleles suggest that they modulate the same event(s) in the first-to-second-step transition, most likely by stabilization of the second-step spliceosome; in contrast, alleles of U6 snRNA that also alter this transition modulate a distinct event, most likely by stabilization of the first-step spliceosome. These results implicate a myb-like domain of Cef1/CDC5 in interactions that modulate conformational states of the spliceosome and suggest that alteration of these events affects splice site use, resulting in alternative splicing-like patterns in yeast. PMID:22408182

Alleles versus mutations: Understanding the evolution of genetic architecture requires a molecular perspective on allelic origins.

PubMed

Remington, David L

2015-12-01

Perspectives on the role of large-effect quantitative trait loci (QTL) in the evolution of complex traits have shifted back and forth over the past few decades. Different sets of studies have produced contradictory insights on the evolution of genetic architecture. I argue that much of the confusion results from a failure to distinguish mutational and allelic effects, a limitation of using the Fisherian model of adaptive evolution as the lens through which the evolution of adaptive variation is examined. A molecular-based perspective reveals that allelic differences can involve the cumulative effects of many mutations plus intragenic recombination, a model that is supported by extensive empirical evidence. I discuss how different selection regimes could produce very different architectures of allelic effects under a molecular-based model, which may explain conflicting insights on genetic architecture from studies of variation within populations versus between divergently selected populations. I address shortcomings of genome-wide association study (GWAS) practices in light of more suitable models of allelic evolution, and suggest alternate GWAS strategies to generate more valid inferences about genetic architecture. Finally, I discuss how adopting more suitable models of allelic evolution could help redirect research on complex trait evolution toward addressing more meaningful questions in evolutionary biology. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

Analysis of natural allelic variation at seed dormancy loci of Arabidopsis thaliana.

PubMed

Alonso-Blanco, Carlos; Bentsink, Leónie; Hanhart, Corrie J; Blankestijn-de Vries, Hetty; Koornneef, Maarten

2003-06-01

Arabidopsis accessions differ largely in their seed dormancy behavior. To understand the genetic basis of this intraspecific variation we analyzed two accessions: the laboratory strain Landsberg erecta (Ler) with low dormancy and the strong-dormancy accession Cape Verde Islands (Cvi). We used a quantitative trait loci (QTL) mapping approach to identify loci affecting the after-ripening requirement measured as the number of days of seed dry storage required to reach 50% germination. Thus, seven QTL were identified and named delay of germination (DOG) 1-7. To confirm and characterize these loci, we developed 12 near-isogenic lines carrying single and double Cvi introgression fragments in a Ler genetic background. The analysis of these lines for germination in water confirmed four QTL (DOG1, DOG2, DOG3, and DOG6) as showing large additive effects in Ler background. In addition, it was found that DOG1 and DOG3 genetically interact, the strong dormancy determined by DOG1-Cvi alleles depending on DOG3-Ler alleles. These genotypes were further characterized for seed dormancy/germination behavior in five other test conditions, including seed coat removal, gibberellins, and an abscisic acid biosynthesis inhibitor. The role of the Ler/Cvi allelic variation in affecting dormancy is discussed in the context of current knowledge of Arabidopsis germination.

LBH Gene Transcription Regulation by the Interplay of an Enhancer Risk Allele and DNA Methylation in Rheumatoid Arthritis.

PubMed

Hammaker, Deepa; Whitaker, John W; Maeshima, Keisuke; Boyle, David L; Ekwall, Anna-Karin H; Wang, Wei; Firestein, Gary S

2016-11-01

To identify nonobvious therapeutic targets for rheumatoid arthritis (RA), we performed an integrative analysis incorporating multiple "omics" data and the Encyclopedia of DNA Elements (ENCODE) database for potential regulatory regions. This analysis identified the limb bud and heart development (LBH) gene, which has risk alleles associated with RA/celiac disease and lupus, and can regulate cell proliferation in RA. We identified a novel LBH transcription enhancer with an RA risk allele (rs906868 G [Ref]/T) 6 kb upstream of the LBH gene with a differentially methylated locus. The confluence of 3 regulatory elements, rs906868, an RA differentially methylated locus, and a putative enhancer, led us to investigate their effects on LBH regulation in fibroblast-like synoviocytes (FLS). We cloned the 1.4-kb putative enhancer with either the rs906868 Ref allele or single-nucleotide polymorphism (SNP) variant into reporter constructs. The constructs were methylated in vitro and transfected into cultured FLS by nucleofection. We found that both variants increased transcription, thereby confirming the region's enhancer function. Unexpectedly, the transcriptional activity of the Ref risk allele was significantly lower than that of the SNP variant and is consistent with low LBH levels as a risk factor for aggressive FLS behavior. Using RA FLS lines with a homozygous Ref or SNP allele, we confirmed that homozygous Ref lines expressed lower LBH messenger RNA levels than did the SNP lines. Methylation significantly reduced enhancer activity for both alleles, indicating that enhancer function is dependent on its methylation status. This study shows how the interplay between genetics and epigenetics can affect expression of LBH in RA. © 2016, American College of Rheumatology.

Combination of Eight Alleles at Four Quantitative Trait Loci Determines Grain Length in Rice

PubMed Central

Zeng, Yuxiang; Ji, Zhijuan; Wen, Zhihua; Liang, Yan; Yang, Changdeng

2016-01-01

Grain length is an important quantitative trait in rice (Oryza sativa L.) that influences both grain yield and exterior quality. Although many quantitative trait loci (QTLs) for grain length have been identified, it is still unclear how different alleles from different QTLs regulate grain length coordinately. To explore the mechanisms of QTL combination in the determination of grain length, five mapping populations, including two F2 populations, an F3 population, an F7 recombinant inbred line (RIL) population, and an F8 RIL population, were developed from the cross between the U.S. tropical japonica variety ‘Lemont’ and the Chinese indica variety ‘Yangdao 4’ and grown under different environmental conditions. Four QTLs (qGL-3-1, qGL-3-2, qGL-4, and qGL-7) for grain length were detected using both composite interval mapping and multiple interval mapping methods in the mapping populations. In each locus, there was an allele from one parent that increased grain length and another allele from another parent that decreased it. The eight alleles in the four QTLs were analyzed to determine whether these alleles act additively across loci, and lead to a linear relationship between the predicted breeding value of QTLs and phenotype. Linear regression analysis suggested that the combination of eight alleles determined grain length. Plants carrying more grain length-increasing alleles had longer grain length than those carrying more grain length-decreasing alleles. This trend was consistent in all five mapping populations and demonstrated the regulation of grain length by the four QTLs. Thus, these QTLs are ideal resources for modifying grain length in rice. PMID:26942914

Prevalence of Atherogenic Dyslipidemia in Spanish Hypertensive Patients and Its Relationship With Blood Pressure Control and Silent Organ Damage.

PubMed

de la Sierra, Alejandro; Gorostidi, Manuel; Aranda, Pedro; Corbella, Emili; Pintó, Xavier

2015-07-01

To assess the prevalence of atherogenic dyslipidemia in hypertensive patients and its relationship with risk profile and blood pressure control. The study included 24 351 hypertensive patients from the Spanish Ambulatory Blood Pressure Monitoring Registry. Atherogenic dyslipidemia was defined as the presence of hypertriglyceridemia (> 150mg/dL) and low levels of high-density lipoprotein cholesterol (< 40mg/dL in men and < 46mg/dL in women). Blood pressure control was assessed by office and ambulatory monitoring. Atherogenic dyslipidemia was present in 2705 patients (11.1%). Of these, 30% had hypertriglyceridemia and 21.7% had low levels of high-density lipoprotein cholesterol. Compared with patients without these risk factors, the former group were more often male (60% vs 52%), younger (57 years vs 59 years), had other risk factors and organ damage (microalbuminuria, reduced estimated glomerular filtration rate, and left ventricular hypertrophy), worse office, diurnal, and nocturnal blood pressure values (odds ratio 1.09, 1.06, and 1.10, respectively), and the lowest nocturnal blood pressure reduction (odds ratio=1.07), despite the greater use of antihypertensive drugs. Atherogenic dyslipidemia is present in more than 10% of hypertensive patients and is associated with other risk factors, organ damage, and poorer blood pressure control. Greater therapeutic effort is needed to reduce overall risk in these patients. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Diabetes, metabolic syndrome and dyslipidemia in people living with HIV in Africa: re-emerging challenges not to be forgotten

PubMed Central

Husain, Nazik Elmalaika; Noor, Sufian K; Elmadhoun, Wadie M; Almobarak, Ahmed O; Awadalla, Heitham; Woodward, Clare L; Mital, Dushyant; Ahmed, Mohamed H

2017-01-01

Background The current challenge in managing people living with human immunodeficiency virus (PLWHIV) includes the identification and monitoring for comorbid health risks associated with HIV and its treatment and longer survival. Dyslipidemia, diabetes mellitus and metabolic syndrome are increasingly seen in PLWHIV. Objective In this narrative review, we aimed to summarize the current knowledge about diabetes, dyslipidemia and metabolic syndrome in PLWHIV in Africa and also to discuss the challenges that patients as well as health authorities in Africa may face. Methods PubMed and Google scholar published-English literatures concerning earlier mentioned entities regardless of time limit were critically reviewed. Results The prevalence of metabolic disorders in HIV population in Africa was estimated to range from 2.1% to 26.5% for diabetes and 20.2% to 43.5% for pre-diabetes, 13% to 58% for metabolic syndrome and 13% to 70% for dyslipidemia. Conclusion The management of metabolic disorders and cardiovascular disease risks related to HIV is complex especially in Africa due to healthcare resources, but our experience suggests that metabolic clinic is beneficial to patients and staff and should be an important part of HIV services especially as the older HIV population is increasing. In this context, cardiovascular risk assessment of HIV-infected patients will become an important component of care in developing countries in Africa and strategies are needed to deal with progressive increase in the epidemic of type 2 diabetes, dyslipidemia and metabolic syndrome. PMID:29184449

Automated analysis of high-throughput B-cell sequencing data reveals a high frequency of novel immunoglobulin V gene segment alleles.

PubMed

Gadala-Maria, Daniel; Yaari, Gur; Uduman, Mohamed; Kleinstein, Steven H

2015-02-24

Individual variation in germline and expressed B-cell immunoglobulin (Ig) repertoires has been associated with aging, disease susceptibility, and differential response to infection and vaccination. Repertoire properties can now be studied at large-scale through next-generation sequencing of rearranged Ig genes. Accurate analysis of these repertoire-sequencing (Rep-Seq) data requires identifying the germline variable (V), diversity (D), and joining (J) gene segments used by each Ig sequence. Current V(D)J assignment methods work by aligning sequences to a database of known germline V(D)J segment alleles. However, existing databases are likely to be incomplete and novel polymorphisms are hard to differentiate from the frequent occurrence of somatic hypermutations in Ig sequences. Here we develop a Tool for Ig Genotype Elucidation via Rep-Seq (TIgGER). TIgGER analyzes mutation patterns in Rep-Seq data to identify novel V segment alleles, and also constructs a personalized germline database containing the specific set of alleles carried by a subject. This information is then used to improve the initial V segment assignments from existing tools, like IMGT/HighV-QUEST. The application of TIgGER to Rep-Seq data from seven subjects identified 11 novel V segment alleles, including at least one in every subject examined. These novel alleles constituted 13% of the total number of unique alleles in these subjects, and impacted 3% of V(D)J segment assignments. These results reinforce the highly polymorphic nature of human Ig V genes, and suggest that many novel alleles remain to be discovered. The integration of TIgGER into Rep-Seq processing pipelines will increase the accuracy of V segment assignments, thus improving B-cell repertoire analyses.

Is nutritional labeling associated with individual health? The effects of labeling-based awareness on dyslipidemia risk in a South Korean population.

PubMed

Kim, Jong Yeob; Kweon, Ki Hong; Kim, Min Jae; Park, Eun-Cheol; Jang, Suk-Yong; Kim, Woorim; Han, Kyu-Tae

2016-09-15

In 1995, the South Korean government made nutrition labeling compulsory, which has positively impacted patients with certain chronic diseases, such as dyslipidemia. We investigated the association between nutrition labeling-based awareness and the risk of dyslipidemia among individuals not yet diagnosed. Our study used data from the fifth Korea National Health and Nutrition Examination Surveys administered during 2010-2014 (n = 17,687). We performed multiple or logistic regression analysis to examine the association between nutritional analysis and various outcome variables. Approximately 70 % of the respondents (n = 11,513) were familiar with nutrition labeling, of which 20 % (n = 3172) decided what food to buy based on that information. This awareness yielded mostly positive results on outcome indicators, such as triglyceride and high-density lipoprotein cholesterol levels. In general, individuals who used nutritional labels to make decisions regarding food purchases had a lower risk of dyslipidemia than individuals who did not (OR: 0.806, 95 % CI: 0.709-0.917). Utilizing nutrition labels for making food choices correlated with a lower risk of dyslipidemia in certain subgroups. Based on our findings, we recommend that health policymakers and medical professionals consider promoting nutrition labeling as an alternative method for managing certain chronic diseases in South Korean patients.

Dietary trans fatty acids intake and its relation to dyslipidemia in a sample of adults in Depok city, West Java, Indonesia.

PubMed

Sartika, Ratu Ayu Dewi

2011-12-01

The Basic Health Research of the Ministry of Health Indonesia in 2008 reported that the single most important cause of death was stroke, in both urban and rural populations. The risk factors underlying the cause of death are associated with hypertension, obesity and dyslipidemia. The purpose of this study was to determine the mean intake of trans fatty acids and its relation to dyslipidemia in a sample of Indonesian adults. A cross-sectional study was conducted on a total of 180 adult male and female respondents aged 35-60 years living in rural and urban areas of Depok city, West Java. Dietary intake was assessed by means of 24-hour recall and semi-quantitative FFQ. The mean intake of trans fatty acids was 0.48% of total calories (urban 0.40% and rural 0.55%). The prevalence of dyslipidemia in the rural and urban subjects were 61.1% and 66.7%, respectively. There was a statistically significant relationship between trans fatty acids intake and hypercholesterolemia and hypertriglyceridemia. The intake of trans fatty acid among the Indonesian adults studied was half the recommended level. The high prevalence of dyslipidemia found indicates the need for intervention to reduce the rising incidence of cardiovascular diseases in Indonesia.

Nucleation and Spread of an Invasive Allele

NASA Astrophysics Data System (ADS)

Korniss, Gyorgy; Caraco, Thomas

2005-03-01

We analyze a prototypical discrete spatial model for the spread of an invasive allele when individuals compete preemptively for common limiting resources. Initially, the population is genetically monomorphic with the resident allele at high density. The invasive allele is introduced through rare, but recurrent, mutation. The mutant allele is the better competitor (has an individual-level advantage) but its spread is limited by the local availability of resources. We find that each successful introduction of the mutant leads to strong spatial clustering. Spatial patterns in simulation resemble nucleation and subsequent growth, articulately described by Avrami's law in sufficiently large systemsootnotetextG. Korniss and T. Caraco, J. Theor. Biol. (in press, 2004); http://www.rpi.edu/ korniss/Research/JTB04.pdf.

An improved assay for the determination of Huntington`s disease allele size

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reeves, C.; Klinger, K.; Miller, G.

1994-09-01

The hallmark of Huntington`s disease (HD) is the expansion of a polymorphic (CAG)n repeat. Several methods have been published describing PCR amplification of this region. Most of these assays require a complex PCR reaction mixture to amplify this GC-rich region. A consistent problem with trinucleotide repeat PCR amplification is the presence of a number of {open_quotes}stutter bands{close_quotes} which may be caused by primer or amplicon slippage during amplification or insufficient polymerase processivity. Most assays for HD arbitrarily select a particular band for diagnostic purposes. Without a clear choice for band selection such an arbitrary selection may result in inconsistent intra-more » or inter-laboratory findings. We present an improved protocol for the amplification of the HD trinucleotide repeat region. This method simplifies the PCR reaction buffer and results in a set of easily identifiable bands from which to determine allele size. HD alleles were identified by selecting bands of clearly greater signal intensity. Stutter banding was much reduced thus permitting easy identification of the most relevant PCR product. A second set of primers internal to the CCG polymorphism was used in selected samples to confirm allele size. The mechanism of action of N,N,N trimethylglycine in the PCR reaction is not clear. It may be possible that the minimal isostabilizing effect of N,N,N trimethylglycine at 2.5 M is significant enough to affect primer specificity. The use of N,N,N trimethylglycine in the PCR reaction facilitated identification of HD alleles and may be appropriate for use in other assays of this type.« less

Somatic Mutation Allelic Ratio Test Using ddPCR (SMART-ddPCR): An Accurate Method for Assessment of Preferential Allelic Imbalance in Tumor DNA.

PubMed

de Smith, Adam J; Walsh, Kyle M; Hansen, Helen M; Endicott, Alyson A; Wiencke, John K; Metayer, Catherine; Wiemels, Joseph L

2015-01-01

The extent to which heritable genetic variants can affect tumor development has yet to be fully elucidated. Tumor selection of single nucleotide polymorphism (SNP) risk alleles, a phenomenon called preferential allelic imbalance (PAI), has been demonstrated in some cancer types. We developed a novel application of digital PCR termed Somatic Mutation Allelic Ratio Test using Droplet Digital PCR (SMART-ddPCR) for accurate assessment of tumor PAI, and have applied this method to test the hypothesis that heritable SNPs associated with childhood acute lymphoblastic leukemia (ALL) may demonstrate tumor PAI. These SNPs are located at CDKN2A (rs3731217) and IKZF1 (rs4132601), genes frequently lost in ALL, and at CEBPE (rs2239633), ARID5B (rs7089424), PIP4K2A (rs10764338), and GATA3 (rs3824662), genes located on chromosomes gained in high-hyperdiploid ALL. We established thresholds of AI using constitutional DNA from SNP heterozygotes, and subsequently measured allelic copy number in tumor DNA from 19-142 heterozygote samples per SNP locus. We did not find significant tumor PAI at these loci, though CDKN2A and IKZF1 SNPs showed a trend towards preferential selection of the risk allele (p = 0.17 and p = 0.23, respectively). Using a genomic copy number control ddPCR assay, we investigated somatic copy number alterations (SCNA) underlying AI at CDKN2A and IKZF1, revealing a complex range of alterations including homozygous and hemizygous deletions and copy-neutral loss of heterozygosity, with varying degrees of clonality. Copy number estimates from ddPCR showed high agreement with those from multiplex ligation-dependent probe amplification (MLPA) assays. We demonstrate that SMART-ddPCR is a highly accurate method for investigation of tumor PAI and for assessment of the somatic alterations underlying AI. Furthermore, analysis of publicly available data from The Cancer Genome Atlas identified 16 recurrent SCNA loci that contain heritable cancer risk SNPs associated with a

Asian patients with dyslipidemia in an urban population: Effect of ethnicity on their LDL-cholesterol treatment goals.

PubMed

Tan, Ngiap Chuan; Koh, Kim Hwee; Goh, Chin Chin; Koh, Yi Ling Eileen; Goh, Soo Chye Paul

2016-01-01

Dyslipidemia is the primary risk factor for arthrosclerosis. It is the most common chronic disease among the multiethnic Asian population in Singapore. Local national health survey has shown ethnic variability in achieving control of dyslipidemia. This study aimed to determine the proportion of patients in primary care, who achieved their low-density lipoprotein (LDL)-cholesterol treatment goals, stratified by the local major ethnic groups. It also evaluated the factors that affected their dyslipidemia control, including diet, exercise and medication usage. Research assistants administered questionnaires on adult patients with physician-diagnosed dyslipidemia to determine their views on diet, exercise, and medications in this cross-sectional study in 2 local primary care clinics. Their lipid profiles were retrieved from their laboratory reports in their electronic health records. Chi-square and Fisher exact tests were used for the categorical demographics and questionnaire variables, (P < .05: statistically significant). Logistic regression was performed using these significant variables to determine the adjusted odds of the ethnic groups. A total of 1093 eligible patients completed the questionnaires. The proportion of Chinese, Malay, and Indian patients who achieved LDL-cholesterol goals was 78.3%, 67.9%, and 68.5%, respectively. Among those who self-reported taking their favorite cholesterol-rich food occasionally when their cholesterol became controlled, 35.8% Indians failed to achieve treatment goals, compared to 20.1% Chinese and 30.9% Malay patients. Regular medication adherence was associated with 81.8% Chinese, 69.0% Malay, and 69.7% Indian reaching treatment goals. More Chinese met LDL-cholesterol treatment goals compared to Malays and Indians. Lipid-lowering medications enabled but smoking hindered their achievement of these treatment goals. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Assigning breed origin to alleles in crossbred animals.

PubMed

Vandenplas, Jérémie; Calus, Mario P L; Sevillano, Claudia A; Windig, Jack J; Bastiaansen, John W M

2016-08-22

For some species, animal production systems are based on the use of crossbreeding to take advantage of the increased performance of crossbred compared to purebred animals. Effects of single nucleotide polymorphisms (SNPs) may differ between purebred and crossbred animals for several reasons: (1) differences in linkage disequilibrium between SNP alleles and a quantitative trait locus; (2) differences in genetic backgrounds (e.g., dominance and epistatic interactions); and (3) differences in environmental conditions, which result in genotype-by-environment interactions. Thus, SNP effects may be breed-specific, which has led to the development of genomic evaluations for crossbred performance that take such effects into account. However, to estimate breed-specific effects, it is necessary to know breed origin of alleles in crossbred animals. Therefore, our aim was to develop an approach for assigning breed origin to alleles of crossbred animals (termed BOA) without information on pedigree and to study its accuracy by considering various factors, including distance between breeds. The BOA approach consists of: (1) phasing genotypes of purebred and crossbred animals; (2) assigning breed origin to phased haplotypes; and (3) assigning breed origin to alleles of crossbred animals based on a library of assigned haplotypes, the breed composition of crossbred animals, and their SNP genotypes. The accuracy of allele assignments was determined for simulated datasets that include crosses between closely-related, distantly-related and unrelated breeds. Across these scenarios, the percentage of alleles of a crossbred animal that were correctly assigned to their breed origin was greater than 90 %, and increased with increasing distance between breeds, while the percentage of incorrectly assigned alleles was always less than 2 %. For the remaining alleles, i.e. 0 to 10 % of all alleles of a crossbred animal, breed origin could not be assigned. The BOA approach accurately assigns

Use of allele scores as instrumental variables for Mendelian randomization

PubMed Central

Burgess, Stephen; Thompson, Simon G

2013-01-01

Background An allele score is a single variable summarizing multiple genetic variants associated with a risk factor. It is calculated as the total number of risk factor-increasing alleles for an individual (unweighted score), or the sum of weights for each allele corresponding to estimated genetic effect sizes (weighted score). An allele score can be used in a Mendelian randomization analysis to estimate the causal effect of the risk factor on an outcome. Methods Data were simulated to investigate the use of allele scores in Mendelian randomization where conventional instrumental variable techniques using multiple genetic variants demonstrate ‘weak instrument’ bias. The robustness of estimates using the allele score to misspecification (for example non-linearity, effect modification) and to violations of the instrumental variable assumptions was assessed. Results Causal estimates using a correctly specified allele score were unbiased with appropriate coverage levels. The estimates were generally robust to misspecification of the allele score, but not to instrumental variable violations, even if the majority of variants in the allele score were valid instruments. Using a weighted rather than an unweighted allele score increased power, but the increase was small when genetic variants had similar effect sizes. Naive use of the data under analysis to choose which variants to include in an allele score, or for deriving weights, resulted in substantial biases. Conclusions Allele scores enable valid causal estimates with large numbers of genetic variants. The stringency of criteria for genetic variants in Mendelian randomization should be maintained for all variants in an allele score. PMID:24062299

Detection of MPLW515L/K Mutations and Determination of Allele Frequencies with a Single-Tube PCR Assay

PubMed Central

Takei, Hiraku; Morishita, Soji; Araki, Marito; Edahiro, Yoko; Sunami, Yoshitaka; Hironaka, Yumi; Noda, Naohiro; Sekiguchi, Yuji; Tsuneda, Satoshi; Ohsaka, Akimichi; Komatsu, Norio

2014-01-01

A gain-of-function mutation in the myeloproliferative leukemia virus (MPL) gene, which encodes the thrombopoietin receptor, has been identified in patients with essential thrombocythemia and primary myelofibrosis, subgroups of classic myeloproliferative neoplasms (MPNs). The presence of MPL gene mutations is a critical diagnostic criterion for these diseases. Here, we developed a rapid, simple, and cost-effective method of detecting two major MPL mutations, MPLW515L/K, in a single PCR assay; we termed this method DARMS (dual amplification refractory mutation system)-PCR. DARMS-PCR is designed to produce three different PCR products corresponding to MPLW515L, MPLW515K, and all MPL alleles. The amplicons are later detected and quantified using a capillary sequencer to determine the relative frequencies of the mutant and wild-type alleles. Applying DARMS-PCR to human specimens, we successfully identified MPL mutations in MPN patients, with the exception of patients bearing mutant allele frequencies below the detection limit (5%) of this method. The MPL mutant allele frequencies determined using DARMS-PCR correlated strongly with the values determined using deep sequencing. Thus, we demonstrated the potential of DARMS-PCR to detect MPL mutations and determine the allele frequencies in a timely and cost-effective manner. PMID:25144224

Detection of MPLW515L/K mutations and determination of allele frequencies with a single-tube PCR assay.

PubMed

Takei, Hiraku; Morishita, Soji; Araki, Marito; Edahiro, Yoko; Sunami, Yoshitaka; Hironaka, Yumi; Noda, Naohiro; Sekiguchi, Yuji; Tsuneda, Satoshi; Ohsaka, Akimichi; Komatsu, Norio

2014-01-01

A gain-of-function mutation in the myeloproliferative leukemia virus (MPL) gene, which encodes the thrombopoietin receptor, has been identified in patients with essential thrombocythemia and primary myelofibrosis, subgroups of classic myeloproliferative neoplasms (MPNs). The presence of MPL gene mutations is a critical diagnostic criterion for these diseases. Here, we developed a rapid, simple, and cost-effective method of detecting two major MPL mutations, MPLW515L/K, in a single PCR assay; we termed this method DARMS (dual amplification refractory mutation system)-PCR. DARMS-PCR is designed to produce three different PCR products corresponding to MPLW515L, MPLW515K, and all MPL alleles. The amplicons are later detected and quantified using a capillary sequencer to determine the relative frequencies of the mutant and wild-type alleles. Applying DARMS-PCR to human specimens, we successfully identified MPL mutations in MPN patients, with the exception of patients bearing mutant allele frequencies below the detection limit (5%) of this method. The MPL mutant allele frequencies determined using DARMS-PCR correlated strongly with the values determined using deep sequencing. Thus, we demonstrated the potential of DARMS-PCR to detect MPL mutations and determine the allele frequencies in a timely and cost-effective manner.

A Simple, High-Throughput Assay for Fragile X Expanded Alleles Using Triple Repeat Primed PCR and Capillary Electrophoresis

PubMed Central

Lyon, Elaine; Laver, Thomas; Yu, Ping; Jama, Mohamed; Young, Keith; Zoccoli, Michael; Marlowe, Natalia

2010-01-01

Population screening has been proposed for Fragile X syndrome to identify premutation carrier females and affected newborns. We developed a PCR-based assay capable of quickly detecting the presence or absence of an expanded FMR1 allele with high sensitivity and specificity. This assay combines a triplet repeat primed PCR with high-throughput automated capillary electrophoresis. We evaluated assay performance using archived samples sent for Fragile X diagnostic testing representing a range of Fragile X CGG-repeat expansions. Two hundred five previously genotyped samples were tested with the new assay. Data were analyzed for the presence of a trinucleotide “ladder” extending beyond 55 repeats, which was set as a cut-off to identify expanded FMR1 alleles. We identified expanded FMR1 alleles in 132 samples (59 premutation, 71 full mutation, 2 mosaics) and normal FMR1 alleles in 73 samples. We found 100% concordance with previous results from PCR and Southern blot analyses. In addition, we show feasibility of using this assay with DNA extracted from dried-blood spots. Using a single PCR combined with high-throughput fragment analysis on the automated capillary electrophoresis instrument, we developed a rapid and reproducible PCR-based laboratory assay that meets many of the requirements for a first-tier test for population screening. PMID:20431035

iRhom2 deficiency relieves TNF-α associated hepatic dyslipidemia in long-term PM2.5-exposed mice.

PubMed

Ge, Chen-Xu; Qin, Yu-Ting; Lou, De-Shuai; Li, Qiang; Li, Yuan-Yuan; Wang, Zhong-Ming; Yang, Wei-Wei; Wang, Ming; Liu, Nan; Wang, Zhen; Zhang, Peng-Xing; Tu, Yan-Yang; Tan, Jun; Xu, Min-Xuan

2017-12-02

Accumulating researches reported that particulate matter (PM2.5) is a risk factor for developing various diseases, including metabolic syndrome. Recently, inactive rhomboid protein 2 (iRhom2) was considered as a necessary modulator for shedding of tumor necrosis factor-α (TNF-α) in immune cells. TNF-α, a major pro-inflammatory cytokine, was linked to various pathogenesis of diseases, including dyslipidemia. Here, wild type (WT) and iRhom2-knockout (iRhom2 -/- ) mice were used to investigate the effects of iRhom2 on PM2.5-induced hepatic dyslipidemia. The hepatic histology, inflammatory response, glucose tolerance, serum parameters and gene expressions were analyzed. We found that long-term inhalation of PM2.5 resulted in hepatic steatosis. And a significant up-regulation of iRhom2 in liver tissues was observed, accompanied with elevated TNF-α, TNF-α converting enzyme (TACE), TNFα receptor (TNFR)2 and various inflammatory cytokines expressions. Additionally, PM2.5 treatment caused TG and TC accumulation in serum and liver, probably attributed to changes of genes modulating lipid metabolism. Intriguingly, hepatic injury and dyslipidemia were attenuated by iRhom2 -/- in mice with PM2.5 challenge. In vitro, iRhom2-knockdwon reduced TNF-α expressions and its associated inflammatory cytokines in Kupffer cells, implying that liver-resident macrophages played an important role in regulating hepatic inflammation and lipid metabolism in cells treated with PM2.5. The findings indicated that long-term PM2.5 exposure caused hepatic steatosis and dyslipidemia through triggering inflammation, which was, at least partly, dependent on iRhom2/TNF-α pathway in liver-resident macrophages. Copyright © 2017 Elsevier Inc. All rights reserved.

Joint effects of hypertension, smoking, dyslipidemia and obesity and angiotensin-converting enzyme DD genotype on albuminuria in Taiwanese patients with type 2 diabetes mellitus.

PubMed

Tseng, Chin-Hsiao; Tseng, Ching-Ping; Chong, Choon-Khim

2010-05-01

We investigated the individual and joint effects of hypertension, smoking, dyslipidemia, and obesity and angiotensin-converting enzyme (ACE) DD genotype on albuminuria in Taiwanese type 2 diabetic patients. ACE genotypes were determined in 519 (287 men and 232 women) patients aged 58.5 (SD: 9.0) years. Among them, 240 had albuminuria (urinary albumin-to-creatinine ratio > or =30 microg/mg). Logistic regression was used to evaluate the individual and joint effects of risk factors and DD classified by two-by-four table. The adjusted odds ratios were significant for hypertension, smoking and obesity but not for DD and dyslipidemia in models evaluating individual effects. However, while analyzing the joint effects of DD and hypertension, smoking, dyslipidemia and obesity, the respective adjusted odds ratios were 3.253 (1.261-8.391), 3.016 (1.086-8.376), 2.385 (1.010-5.630) and 2.508 (1.117-5.631). Hypertension, smoking, dyslipidemia and obesity jointly play an important role with DD genotype in mediating albuminuria. 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Trans-Ethnic Fine-Mapping of Lipid Loci Identifies Population-Specific Signals and Allelic Heterogeneity That Increases the Trait Variance Explained

PubMed Central

Wu, Ying; Waite, Lindsay L.; Jackson, Anne U.; Sheu, Wayne H-H.; Buyske, Steven; Absher, Devin; Arnett, Donna K.; Boerwinkle, Eric; Bonnycastle, Lori L.; Carty, Cara L.; Cheng, Iona; Cochran, Barbara; Croteau-Chonka, Damien C.; Dumitrescu, Logan; Eaton, Charles B.; Franceschini, Nora; Guo, Xiuqing; Henderson, Brian E.; Hindorff, Lucia A.; Kim, Eric; Kinnunen, Leena; Komulainen, Pirjo; Lee, Wen-Jane; Le Marchand, Loic; Lin, Yi; Lindström, Jaana; Lingaas-Holmen, Oddgeir; Mitchell, Sabrina L.; Narisu, Narisu; Robinson, Jennifer G.; Schumacher, Fred; Stančáková, Alena; Sundvall, Jouko; Sung, Yun-Ju; Swift, Amy J.; Wang, Wen-Chang; Wilkens, Lynne; Wilsgaard, Tom; Young, Alicia M.; Adair, Linda S.; Ballantyne, Christie M.; Bůžková, Petra; Chakravarti, Aravinda; Collins, Francis S.; Duggan, David; Feranil, Alan B.; Ho, Low-Tone; Hung, Yi-Jen; Hunt, Steven C.; Hveem, Kristian; Juang, Jyh-Ming J.; Kesäniemi, Antero Y.; Kuusisto, Johanna; Laakso, Markku; Lakka, Timo A.; Lee, I-Te; Leppert, Mark F.; Matise, Tara C.; Moilanen, Leena; Njølstad, Inger; Peters, Ulrike; Quertermous, Thomas; Rauramaa, Rainer; Rotter, Jerome I.; Saramies, Jouko; Tuomilehto, Jaakko; Uusitupa, Matti; Wang, Tzung-Dau; Mohlke, Karen L.

2013-01-01

Genome-wide association studies (GWAS) have identified ∼100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individuals of African American (n = 6,832), East Asian (n = 9,449), and European (n = 10,829) ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P<1×10−4 in at least one ancestry group. Sequential conditional analyses revealed that ten, nine, and four loci in African Americans, Europeans, and East Asians, respectively, exhibited two or more signals. At these loci, accounting for all signals led to a 1.3- to 1.8-fold increase in the explained phenotypic variance compared to the strongest signals. Distinct signals across ancestry groups were identified at PCSK9 and APOA5. Trans-ethnic analyses narrowed the signals to smaller sets of variants at GCKR, PPP1R3B, ABO, LCAT, and ABCA1. Of 27 variants reported previously to have functional effects, 74% exhibited the strongest association at the respective signal. In conclusion, trans-ethnic high-density genotyping and analysis confirm the presence of allelic heterogeneity, allow the identification of population-specific variants, and limit the number of candidate SNPs for functional studies. PMID:23555291

Is the Physician’s Behavior in Dyslipidemia Diagnosis in Accordance with Guidelines? Cross-Sectional Escarval Study

PubMed Central

Palazón-Bru, Antonio; Gil-Guillén, Vicente F.; Orozco-Beltrán, Domingo; Pallarés-Carratalá, Vicente; Valls-Roca, Francisco; Sanchís-Domenech, Carlos; Martín-Moreno, José M.; Redón, Josep; Navarro-Pérez, Jorge; Fernández-Giménez, Antonio; Pérez-Navarro, Ana M.; Trillo, José L.; Usó, Ruth; Ruiz, Elías

2014-01-01

Background Clinical inertia has been defined as mistakes by the physician in starting or intensifying treatment when indicated. Inertia, therefore, can affect other stages in the healthcare process, like diagnosis. The diagnosis of dyslipidemia requires ≥2 high lipid values, but inappropriate behavior in the diagnosis of dyslipidemia has only previously been analyzed using just total cholesterol (TC). Objectives To determine clinical inertia in the dyslipidemia diagnosis using both TC and high-density lipoprotein cholesterol (HDL-c) and its associated factors. Design Cross-sectional. Setting All health center visits in the second half of 2010 in the Valencian Community (Spain). Patients 11,386 nondyslipidemic individuals aged ≥20 years with ≥2 lipid determinations. Measurement Variables Gender, atrial fibrillation, hypertension, diabetes, cardiovascular disease, age, and ESCARVAL training course. Lipid groups: normal (TC<5.17 mmol/L and normal HDL-c [≥1.03 mmol/L in men and ≥1.29 mmol/L in women], TC inertia (TC≥5.17 mmol/L and normal HDL-c), HDL-c inertia (TC<5.17 mmol/L and low HDL-c), and combined inertia (TC≥5.17 mmol/L and low HDL-c). Results TC inertia: 38.0% (95% CI: 37.2–38.9%); HDL-c inertia: 17.7% (95% CI: 17.0–18.4%); and combined inertia: 9.6% (95% CI: 9.1–10.2%). The profile associated with TC inertia was: female, no cardiovascular risk factors, no cardiovascular disease, middle or advanced age; for HDL-c inertia: female, cardiovascular risk factors and cardiovascular disease; and for combined inertia: female, hypertension and middle age. Limitations Cross-sectional study, under-reporting, no analysis of some cardiovascular risk factors or other lipid parameters. Conclusions A more proactive attitude should be adopted, focusing on the full diagnosis of dyslipidemia in clinical practice. Special emphasis should be placed on patients with low HDL-c levels and an increased cardiovascular risk. PMID:24626597

Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction.

PubMed

Do, Ron; Stitziel, Nathan O; Won, Hong-Hee; Jørgensen, Anders Berg; Duga, Stefano; Angelica Merlini, Pier; Kiezun, Adam; Farrall, Martin; Goel, Anuj; Zuk, Or; Guella, Illaria; Asselta, Rosanna; Lange, Leslie A; Peloso, Gina M; Auer, Paul L; Girelli, Domenico; Martinelli, Nicola; Farlow, Deborah N; DePristo, Mark A; Roberts, Robert; Stewart, Alexander F R; Saleheen, Danish; Danesh, John; Epstein, Stephen E; Sivapalaratnam, Suthesh; Hovingh, G Kees; Kastelein, John J; Samani, Nilesh J; Schunkert, Heribert; Erdmann, Jeanette; Shah, Svati H; Kraus, William E; Davies, Robert; Nikpay, Majid; Johansen, Christopher T; Wang, Jian; Hegele, Robert A; Hechter, Eliana; Marz, Winfried; Kleber, Marcus E; Huang, Jie; Johnson, Andrew D; Li, Mingyao; Burke, Greg L; Gross, Myron; Liu, Yongmei; Assimes, Themistocles L; Heiss, Gerardo; Lange, Ethan M; Folsom, Aaron R; Taylor, Herman A; Olivieri, Oliviero; Hamsten, Anders; Clarke, Robert; Reilly, Dermot F; Yin, Wu; Rivas, Manuel A; Donnelly, Peter; Rossouw, Jacques E; Psaty, Bruce M; Herrington, David M; Wilson, James G; Rich, Stephen S; Bamshad, Michael J; Tracy, Russell P; Cupples, L Adrienne; Rader, Daniel J; Reilly, Muredach P; Spertus, John A; Cresci, Sharon; Hartiala, Jaana; Tang, W H Wilson; Hazen, Stanley L; Allayee, Hooman; Reiner, Alex P; Carlson, Christopher S; Kooperberg, Charles; Jackson, Rebecca D; Boerwinkle, Eric; Lander, Eric S; Schwartz, Stephen M; Siscovick, David S; McPherson, Ruth; Tybjaerg-Hansen, Anne; Abecasis, Goncalo R; Watkins, Hugh; Nickerson, Deborah A; Ardissino, Diego; Sunyaev, Shamil R; O'Donnell, Christopher J; Altshuler, David; Gabriel, Stacey; Kathiresan, Sekar

2015-02-05

Myocardial infarction (MI), a leading cause of death around the world, displays a complex pattern of inheritance. When MI occurs early in life, genetic inheritance is a major component to risk. Previously, rare mutations in low-density lipoprotein (LDL) genes have been shown to contribute to MI risk in individual families, whereas common variants at more than 45 loci have been associated with MI risk in the population. Here we evaluate how rare mutations contribute to early-onset MI risk in the population. We sequenced the protein-coding regions of 9,793 genomes from patients with MI at an early age (≤50 years in males and ≤60 years in females) along with MI-free controls. We identified two genes in which rare coding-sequence mutations were more frequent in MI cases versus controls at exome-wide significance. At low-density lipoprotein receptor (LDLR), carriers of rare non-synonymous mutations were at 4.2-fold increased risk for MI; carriers of null alleles at LDLR were at even higher risk (13-fold difference). Approximately 2% of early MI cases harbour a rare, damaging mutation in LDLR; this estimate is similar to one made more than 40 years ago using an analysis of total cholesterol. Among controls, about 1 in 217 carried an LDLR coding-sequence mutation and had plasma LDL cholesterol > 190 mg dl(-1). At apolipoprotein A-V (APOA5), carriers of rare non-synonymous mutations were at 2.2-fold increased risk for MI. When compared with non-carriers, LDLR mutation carriers had higher plasma LDL cholesterol, whereas APOA5 mutation carriers had higher plasma triglycerides. Recent evidence has connected MI risk with coding-sequence mutations at two genes functionally related to APOA5, namely lipoprotein lipase and apolipoprotein C-III (refs 18, 19). Combined, these observations suggest that, as well as LDL cholesterol, disordered metabolism of triglyceride-rich lipoproteins contributes to MI risk.

Schizophrenia and neurotrophin-3 alleles.

PubMed

Jŏnsson, E; Brené, S; Zhang, X R; Nimgaonkar, V L; Tylec, A; Schalling, M; Sedvall, G

1997-05-01

Studies of brain anatomy and premorbid functioning indicate that schizophrenia may be of neurodevelopmental origin. In the neurotrophic factor neurotrophin-3 (NT-3) gene, the A3/147-bp allele in a dinucleotide repeat polymorphism located in the promoter region was found to be associated with schizophrenia in a Japanese study. Another NT-3 polymorphism (Glu63Gly) indicated an association with schizophrenic patients with a putative neurodevelopmental form of the disease. We examined Swedish schizophrenic patients (n = 109) and control subjects (n = 78) for the same two NT-3 polymorphisms, as well as a third silent exonic polymorphism (at Pro55). No significant difference was found between the two groups. However, in a meta-analysis including the present and previous studies of Caucasian subjects, the A3/147-bp allele frequency was found to be significantly higher in the schizophrenic patients. In the present study, carriers of the A3/147 bp allele tended to have an earlier age of onset and to display more extrapyramidal symptoms. In the silent exonic polymorphism (at Pro55), female schizophrenic patients had higher adenine and lower guanine allele frequencies than control female subjects. Together with previous studies, the results provide some support for an association between the NT-3 gene and certain forms of schizophrenia. This warrants further investigation of NT-3 and other neurotrophic factors with additional polymorphisms and larger patient samples.

Cholesteryl Ester Transfer Protein Intimately Involved in Dyslipidemia-Related Susceptibility to Cognitive Deficits in Type 2 Diabetic Patients.

PubMed

Sun, Jie; Cai, Rongrong; Huang, Rong; Wang, Pin; Tian, Sai; Sun, Haixia; Xia, Wenqing; Wang, Shaohua

2016-08-01

Cholesteryl ester transfer protein (CETP) is involved in diabetic dyslipidemia. We aim to test the hypothesis that CETP might be of importance in mediating dyslipidemia-related susceptibility to cognitive deficits in diabetic patients. We recruited 190 type 2 diabetic patients and divided them into two groups according to the Montreal Cognitive Assessment (MoCA) score. The association between CETP and cognitive decline was analyzed with logistic regression and stratification. There were 110 diabetic patients with mild cognition impairment (MCI) and 80 healthy cognition subjects as controls. Dyslipidemia is more common among diabetic patients with MCI; they had a significant increase of serum CETP concentrations, which was negatively correlated with MoCA (r = -0.638; p < 0.001). Negative correlations were also found between the serum CETP concentration with the Auditory Verbal Learning Test (r = -0.266; p = 0.008), indicating memory deficit. Logistic regression analysis revealed that CETP concentration was an independent factor of diabetic MCI (p < 0.001). Further stratification study showed that high serum levels of CETP was an independent risk factor of MCI in diabetic patients with a low density lipoproteins level ≥2.59 mmol/L, or high density lipoproteins level ≤1.0 mmol/L for men and ≤1.3 mmol/L for women, or TG level ≥1.7 mmol/L, after adjusting for age, sex, education, and glucose control (all ps < 0.05). CETP was intimately involved in dyslipidemia-related susceptibility to cognitive decline, especially memory function in type 2 diabetic patients.

Influence of Human Leukocyte Antigen (HLA) Alleles and Killer Cell Immunoglobulin-Like Receptors (KIR) Types on Heparin-Induced Thrombocytopenia (HIT).

PubMed

Karnes, Jason H; Shaffer, Christian M; Cronin, Robert; Bastarache, Lisa; Gaudieri, Silvana; James, Ian; Pavlos, Rebecca; Steiner, Heidi E; Mosley, Jonathan D; Mallal, Simon; Denny, Joshua C; Phillips, Elizabeth J; Roden, Dan M

2017-09-01

Heparin-induced thrombocytopenia (HIT) is an unpredictable, life-threatening, immune-mediated reaction to heparin. Variation in human leukocyte antigen (HLA) genes is now used to prevent immune-mediated adverse drug reactions. Combinations of HLA alleles and killer cell immunoglobulin-like receptors (KIR) are associated with multiple autoimmune diseases and infections. The objective of this study is to evaluate the association of HLA alleles and KIR types, alone or in the presence of different HLA ligands, with HIT. HIT cases and heparin-exposed controls were identified in BioVU, an electronic health record coupled to a DNA biobank. HLA sequencing and KIR type imputation using Illumina OMNI-Quad data were performed. Odds ratios for HLA alleles and KIR types and HLA*KIR interactions using conditional logistic regressions were determined in the overall population and by race/ethnicity. Analysis was restricted to KIR types and HLA alleles with a frequency greater than 0.01. The p values for HLA and KIR association were corrected by using a false discovery rate q<0.05 and HLA*KIR interactions were considered significant at p<0.05. Sixty-five HIT cases and 350 matched controls were identified. No statistical differences in baseline characteristics were observed between cases and controls. The HLA-DRB3*01:01 allele was significantly associated with HIT in the overall population (odds ratio 2.81 [1.57-5.02], p=2.1×10 -4 , q=0.02) and in individuals with European ancestry, independent of other alleles. No KIR types were associated with HIT, although a significant interaction was observed between KIR2DS5 and the HLA-C1 KIR binding group (p=0.03). The HLA-DRB3*01:01 allele was identified as a potential risk factor for HIT. This class II HLA gene and allele represent biologically plausible candidates for influencing HIT pathogenesis. We found limited evidence of the role of KIR types in HIT pathogenesis. Replication and further study of the HLA-DRB3*01:01 association is

Analysis of natural allelic variation at seed dormancy loci of Arabidopsis thaliana.

PubMed Central

Alonso-Blanco, Carlos; Bentsink, Leónie; Hanhart, Corrie J; Blankestijn-de Vries, Hetty; Koornneef, Maarten

2003-01-01

Arabidopsis accessions differ largely in their seed dormancy behavior. To understand the genetic basis of this intraspecific variation we analyzed two accessions: the laboratory strain Landsberg erecta (Ler) with low dormancy and the strong-dormancy accession Cape Verde Islands (Cvi). We used a quantitative trait loci (QTL) mapping approach to identify loci affecting the after-ripening requirement measured as the number of days of seed dry storage required to reach 50% germination. Thus, seven QTL were identified and named delay of germination (DOG) 1-7. To confirm and characterize these loci, we developed 12 near-isogenic lines carrying single and double Cvi introgression fragments in a Ler genetic background. The analysis of these lines for germination in water confirmed four QTL (DOG1, DOG2, DOG3, and DOG6) as showing large additive effects in Ler background. In addition, it was found that DOG1 and DOG3 genetically interact, the strong dormancy determined by DOG1-Cvi alleles depending on DOG3-Ler alleles. These genotypes were further characterized for seed dormancy/germination behavior in five other test conditions, including seed coat removal, gibberellins, and an abscisic acid biosynthesis inhibitor. The role of the Ler/Cvi allelic variation in affecting dormancy is discussed in the context of current knowledge of Arabidopsis germination. PMID:12807791

Variant-specific quantification of factor H in plasma reveals null alleles associated with atypical hemolytic uremic syndrome

PubMed Central

Hakobyan, Svetlana; Tortajada, Agustín; Harris, Claire L.; de Córdoba, Santiago Rodríguez; Morgan, B. Paul

2011-01-01

Atypical hemolytic uremic syndrome (aHUS) associates with complement alternative pathway defects in over 50% of cases. Mutations in factor H (fH) are most common, usually point mutations affecting complement surface regulation and sometimes null mutations in heterozygosity. The latter are difficult to identify; although consistently low plasma fH concentration is suggestive, definitive proof has required the demonstration that the mutant sequence does not express in vitro. Here, novel reagents and assays that distinguish and individually quantify the common fH-Y402H polymorphic variants were used to identify alleles of the CFH gene resulting in low or no (‘null’) expression of full-length fH, but normal or increased expression of the alternative splice product FHL-1, also detected in these assays. Their use in an aHUS cohort identified three Y402H heterozygotes with low or absent fH-H402 but normal or increased FHL-1 levels. Novel mutations in heterozygosis explained the null phenotype in two cases, confirmed by family studies in one. In the third case, family studies showed that a known mutation was present on the Y allele; the cause of the reduced expression of H allele was not found, although data suggested altered fH/FHL-1 splicing. In each family, inheritance of “low expression” or “null” alleles for fH strongly associated with aHUS. These assays provide a rapid means to identify fH expression defects in aHUS without resorting to gene sequencing or expression analysis. PMID:20703214

Sarcopenia and sarcopenic obesity and their association with dyslipidemia in Korean elderly men: the 2008-2010 Korea National Health and Nutrition Examination Survey.

PubMed

Baek, S J; Nam, G E; Han, K D; Choi, S W; Jung, S W; Bok, A R; Kim, Y H; Lee, K S; Han, B D; Kim, D H

2014-03-01

Recently, aging has been shown to be associated with sarcopenic obesity (SO), of which decreased muscle mass and increased fat mass are features. Sarcopenia and obesity alone are known to be associated with abnormal lipid metabolism. However, it remains unclear whether SO has greater adverse effects on dyslipidemia than on sarcopenia or obesity alone. We aimed to investigate the association between SO and dyslipidemia in elderly Koreans. This study was based on data collected during the 2008-2010 Korea National Health and Nutrition Examination Survey. We included 1,466 men and 2,017 women aged 65 years and over. Sarcopenia was indicated in participants with height- or weight-adjusted appendicular skeletal muscle that was 1 standard deviation below the sex-specific mean for the young reference group, and obesity was defined as a body mass index ≥ 25 kg/m(2). Dyslipidemia was defined according to the National Cholesterol Education Program-Adult Treatment Panel III. After adjusting for confounding factors, the SO group had a higher risk for dyslipidemia [odds ratio (OR) 2.82 (95 % confidence interval 1.76-4.51)] than the obese group [2.12 (1.11-4.07)] and sarcopenic group [1.46 (1.01-2.11)] (p < 0.001) only in men. Furthermore, the SO group in men had the highest OR for hypercholesterolemia, hypertriglyceridemia, hypo-high-density lipoprotein cholesterolemia, hyper-low-density lipoprotein cholesterolemia, and a high ratio of triglyceride to high-density lipoprotein cholesterol even after further adjustments. In Korean elderly men, SO was associated with an increased risk for dyslipidemia compared with sarcopenia or obesity alone.

Robust Identification of Local Adaptation from Allele Frequencies

PubMed Central

Günther, Torsten; Coop, Graham

2013-01-01

Comparing allele frequencies among populations that differ in environment has long been a tool for detecting loci involved in local adaptation. However, such analyses are complicated by an imperfect knowledge of population allele frequencies and neutral correlations of allele frequencies among populations due to shared population history and gene flow. Here we develop a set of methods to robustly test for unusual allele frequency patterns and correlations between environmental variables and allele frequencies while accounting for these complications based on a Bayesian model previously implemented in the software Bayenv. Using this model, we calculate a set of “standardized allele frequencies” that allows investigators to apply tests of their choice to multiple populations while accounting for sampling and covariance due to population history. We illustrate this first by showing that these standardized frequencies can be used to detect nonparametric correlations with environmental variables; these correlations are also less prone to spurious results due to outlier populations. We then demonstrate how these standardized allele frequencies can be used to construct a test to detect SNPs that deviate strongly from neutral population structure. This test is conceptually related to FST and is shown to be more powerful, as we account for population history. We also extend the model to next-generation sequencing of population pools—a cost-efficient way to estimate population allele frequencies, but one that introduces an additional level of sampling noise. The utility of these methods is demonstrated in simulations and by reanalyzing human SNP data from the Human Genome Diversity Panel populations and pooled next-generation sequencing data from Atlantic herring. An implementation of our method is available from http://gcbias.org. PMID:23821598

Uneven segregation of sporophytic self-incompatibility alleles in Arabidopsis lyrata.

PubMed

Bechsgaard, J; Bataillon, T; Schierup, M H

2004-05-01

Self-incompatibility in Arabidopsis lyrata is sporophytically controlled by the multi-allelic S-locus. Self-incompatibility alleles (S-alleles) are under strong negative frequency dependent selection because pollen carrying common S-alleles have fewer mating opportunities. Population genetics theory predicts that deleterious alleles can accumulate if linked to the S-locus. This was tested by studying segregation of S-alleles in 11 large full sib families in A. lyrata. Significant segregation distortion leading to an up to fourfold difference in transmission rates was found in six families. Differences in transmission rates were not significantly different in reciprocal crosses and the distortions observed were compatible with selection acting at the gametic stage alone. The S-allele with the largest segregation advantage is also the most recessive, and is very common in natural populations concordant with its apparent segregation advantage. These results imply that frequencies of S-alleles in populations of A. lyrata cannot be predicted based on simple models of frequency-dependent selection alone.

Allelic variants of hereditary prions: The bimodularity principle.

PubMed

Tikhodeyev, Oleg N; Tarasov, Oleg V; Bondarev, Stanislav A

2017-01-02

Modern biology requires modern genetic concepts equally valid for all discovered mechanisms of inheritance, either "canonical" (mediated by DNA sequences) or epigenetic. Applying basic genetic terms such as "gene" and "allele" to protein hereditary factors is one of the necessary steps toward these concepts. The basic idea that different variants of the same prion protein can be considered as alleles has been previously proposed by Chernoff and Tuite. In this paper, the notion of prion allele is further developed. We propose the idea that any prion allele is a bimodular hereditary system that depends on a certain DNA sequence (DNA determinant) and a certain epigenetic mark (epigenetic determinant). Alteration of any of these 2 determinants may lead to establishment of a new prion allele. The bimodularity principle is valid not only for hereditary prions; it seems to be universal for any epigenetic hereditary factor.

Analysis of novel sph (spherocytosis) alleles in mice reveals allele-specific loss of band 3 and adducin in α-spectrin–deficient red cells

PubMed Central

Robledo, Raymond F.; Lambert, Amy J.; Birkenmeier, Connie S.; Cirlan, Marius V.; Cirlan, Andreea Flavia M.; Campagna, Dean R.; Lux, Samuel E.

2010-01-01

Five spontaneous, allelic mutations in the α-spectrin gene, Spna1, have been identified in mice (spherocytosis [sph], sph1J, sph2J, sph2BC, sphDem). All cause severe hemolytic anemia. Here, analysis of 3 new alleles reveals previously unknown consequences of red blood cell (RBC) spectrin deficiency. In sph3J, a missense mutation (H2012Y) in repeat 19 introduces a cryptic splice site resulting in premature termination of translation. In sphIhj, a premature stop codon occurs (Q1853Stop) in repeat 18. Both mutations result in markedly reduced RBC membrane spectrin content, decreased band 3, and absent β-adducin. Reevaluation of available, previously described sph alleles reveals band 3 and adducin deficiency as well. In sph4J, a missense mutation occurs in the C-terminal EF hand domain (C2384Y). Notably, an equally severe hemolytic anemia occurs despite minimally decreased membrane spectrin with normal band 3 levels and present, although reduced, β-adducin. The severity of anemia in sph4J indicates that the highly conserved cysteine residue at the C-terminus of α-spectrin participates in interactions critical to membrane stability. The data reinforce the notion that a membrane bridge in addition to the classic protein 4.1-p55-glycophorin C linkage exists at the RBC junctional complex that involves interactions between spectrin, adducin, and band 3. PMID:20056793

Analysis of novel sph (spherocytosis) alleles in mice reveals allele-specific loss of band 3 and adducin in alpha-spectrin-deficient red cells.

PubMed

Robledo, Raymond F; Lambert, Amy J; Birkenmeier, Connie S; Cirlan, Marius V; Cirlan, Andreea Flavia M; Campagna, Dean R; Lux, Samuel E; Peters, Luanne L

2010-03-04

Five spontaneous, allelic mutations in the alpha-spectrin gene, Spna1, have been identified in mice (spherocytosis [sph], sph(1J), sph(2J), sph(2BC), sph(Dem)). All cause severe hemolytic anemia. Here, analysis of 3 new alleles reveals previously unknown consequences of red blood cell (RBC) spectrin deficiency. In sph(3J), a missense mutation (H2012Y) in repeat 19 introduces a cryptic splice site resulting in premature termination of translation. In sph(Ihj), a premature stop codon occurs (Q1853Stop) in repeat 18. Both mutations result in markedly reduced RBC membrane spectrin content, decreased band 3, and absent beta-adducin. Reevaluation of available, previously described sph alleles reveals band 3 and adducin deficiency as well. In sph(4J), a missense mutation occurs in the C-terminal EF hand domain (C2384Y). Notably, an equally severe hemolytic anemia occurs despite minimally decreased membrane spectrin with normal band 3 levels and present, although reduced, beta-adducin. The severity of anemia in sph(4J) indicates that the highly conserved cysteine residue at the C-terminus of alpha-spectrin participates in interactions critical to membrane stability. The data reinforce the notion that a membrane bridge in addition to the classic protein 4.1-p55-glycophorin C linkage exists at the RBC junctional complex that involves interactions between spectrin, adducin, and band 3.

TBX6 Null Variants and a Common Hypomorphic Allele in Congenital Scoliosis

PubMed Central

Wu, N.; Ming, X.; Xiao, J.; Wu, Z.; Chen, X.; Shinawi, M.; Shen, Y.; Yu, G.; Liu, J.; Xie, H.; Gucev, Z.S.; Liu, S.; Yang, N.; Al-Kateb, H.; Chen, J.; Zhang, Jian; Hauser, N.; Zhang, T.; Tasic, V.; Liu, P.; Su, X.; Pan, X.; Liu, C.; Wang, L.; Shen, Joseph; Shen, Jianxiong; Chen, Y.; Zhang, T.; Zhang, Jianguo; Choy, K.W.; Wang, Jun; Wang, Q.; Li, S.; Zhou, W.; Guo, J.; Wang, Y.; Zhang, C.; Zhao, H.; An, Y.; Zhao, Y.; Wang, Jiucun; Liu, Z.; Zuo, Y.; Tian, Y.; Weng, X.; Sutton, V.R.; Wang, H.; Ming, Y.; Kulkarni, S.; Zhong, T.P.; Giampietro, P.F.; Dunwoodie, S.L.; Cheung, S.W.; Zhang, X.; Jin, L.; Lupski, J.R.; Qiu, G.; Zhang, F.

2015-01-01

BACKGROUND Congenital scoliosis is a common type of vertebral malformation. Genetic susceptibility has been implicated in congenital scoliosis. METHODS We evaluated 161 Han Chinese persons with sporadic congenital scoliosis, 166 Han Chinese controls, and 2 pedigrees, family members of which had a 16p11.2 deletion, using comparative genomic hybridization, quantitative polymerase-chain-reaction analysis, and DNA sequencing. We carried out tests of replication using an additional series of 76 Han Chinese persons with congenital scoliosis and a multi-center series of 42 persons with 16p11.2 deletions. RESULTS We identified a total of 17 heterozygous TBX6 null mutations in the 161 persons with sporadic congenital scoliosis (11%); we did not observe any null mutations in TBX6 in 166 controls (P<3.8×10−6). These null alleles include copy-number variants (12 instances of a 16p11.2 deletion affecting TBX6) and single-nucleotide variants (1 nonsense and 4 frame-shift mutations). However, the discordant intrafamilial phenotypes of 16p11.2 deletion carriers suggest that heterozygous TBX6 null mutation is insufficient to cause congenital scoliosis. We went on to identify a common TBX6 haplotype as the second risk allele in all 17 carriers of TBX6 null mutations (P<1.1×10−6). Replication studies involving additional persons with congenital scoliosis who carried a deletion affecting TBX6 confirmed this compound inheritance model. In vitro functional assays suggested that the risk haplotype is a hypomorphic allele. Hemivertebrae are characteristic of TBX6-associated congenital scoliosis. CONCLUSIONS Compound inheritance of a rare null mutation and a hypomorphic allele of TBX6 accounted for up to 11% of congenital scoliosis cases in the series that we analyzed. PMID:25564734

Existence of the rdl mutant alleles among the anopheles malaria vector in Indonesia

PubMed Central

2012-01-01

Background The gamma-aminobutyric acid (GABA) receptor-chloride channel complex is known to be the target site of dieldrin, a cyclodiene insecticide. GABA-receptors, with a naturally occurring amino acid substitution, A302S/G in the putative ion-channel lining region, confer resistance to cyclodiene insecticides that includes aldrin, chlordane, dieldrin, heptachlor, endrin and endosulphan. Methods A total of 154 mosquito samples from 10 provinces of malaria-endemic areas across Indonesia (Aceh, North Sumatra, Bangka Belitung, Lampung, Central Java, East Nusa Tenggara, West Nusa Tenggara, West Sulawesi, Molucca and North Molucca) were obtained and identified by species, using morphological characteristic. The DNA was individually extracted using chelex-ion exchanger and the DNA obtained was used for analyses using sequencing method. Results Molecular analysis indicated 11% of the total 154 Anopheles samples examined, carried Rdl mutant alleles. All of the alleles were found in homozygous form. Rdl 302S allele was observed in Anopheles vagus (from Central Java, Lampung, and West Nusa Tenggara), Anopheles aconitus (from Central Java), Anopheles barbirostris (from Central Java and Lampung), Anopheles sundaicus (from North Sumatra and Lampung), Anopheles nigerrimus (from North Sumatra), whereas the 302 G allele was only found in Anopheles farauti from Molucca. Conclusion The existence of the Rdl mutant allele indicates that, either insecticide pressure on the Anopheles population in these areas might still be ongoing (though not directly associated with the malaria control programme) or that the mutant form of the Rdl allele is relatively stable in the absence of insecticide. Nonetheless, the finding suggests that integrated pest management is warranted in malaria-endemic areas where insecticides are widely used for other purposes. PMID:22364613

Existence of the rdl mutant alleles among the anopheles malaria vector in Indonesia.

PubMed

Asih, Puji Bs; Syahrani, Lepa; Rozi, Ismail Ep; Pratama, Nandha R; Marantina, Sylvia S; Arsyad, Dian S; Mangunwardoyo, Wibowo; Hawley, William; Laihad, Ferdinand; Shinta; Sukowati, Supratman; Lobo, Neil F; Syafruddin, Din

2012-02-25

The gamma-aminobutyric acid (GABA) receptor-chloride channel complex is known to be the target site of dieldrin, a cyclodiene insecticide. GABA-receptors, with a naturally occurring amino acid substitution, A302S/G in the putative ion-channel lining region, confer resistance to cyclodiene insecticides that includes aldrin, chlordane, dieldrin, heptachlor, endrin and endosulphan. A total of 154 mosquito samples from 10 provinces of malaria-endemic areas across Indonesia (Aceh, North Sumatra, Bangka Belitung, Lampung, Central Java, East Nusa Tenggara, West Nusa Tenggara, West Sulawesi, Molucca and North Molucca) were obtained and identified by species, using morphological characteristic. The DNA was individually extracted using chelex-ion exchanger and the DNA obtained was used for analyses using sequencing method. Molecular analysis indicated 11% of the total 154 Anopheles samples examined, carried Rdl mutant alleles. All of the alleles were found in homozygous form. Rdl 302S allele was observed in Anopheles vagus (from Central Java, Lampung, and West Nusa Tenggara), Anopheles aconitus (from Central Java), Anopheles barbirostris (from Central Java and Lampung), Anopheles sundaicus (from North Sumatra and Lampung), Anopheles nigerrimus (from North Sumatra), whereas the 302 G allele was only found in Anopheles farauti from Molucca. The existence of the Rdl mutant allele indicates that, either insecticide pressure on the Anopheles population in these areas might still be ongoing (though not directly associated with the malaria control programme) or that the mutant form of the Rdl allele is relatively stable in the absence of insecticide. Nonetheless, the finding suggests that integrated pest management is warranted in malaria-endemic areas where insecticides are widely used for other purposes.

An In-Depth Characterization of the Major Psoriasis Susceptibility Locus Identifies Candidate Susceptibility Alleles within an HLA-C Enhancer Element

PubMed Central

Clop, Alex; Bertoni, Anna; Spain, Sarah L.; Simpson, Michael A.; Pullabhatla, Venu; Tonda, Raul; Hundhausen, Christian; Di Meglio, Paola; De Jong, Pieter; Hayday, Adrian C.; Nestle, Frank O.; Barker, Jonathan N.; Bell, Robert J. A.; Capon, Francesca; Trembath, Richard C.

2013-01-01

Psoriasis is an immune-mediated skin disorder that is inherited as a complex genetic trait. Although genome-wide association scans (GWAS) have identified 36 disease susceptibility regions, more than 50% of the genetic variance can be attributed to a single Major Histocompatibility Complex (MHC) locus, known as PSORS1. Genetic studies indicate that HLA-C is the strongest PSORS1 candidate gene, since markers tagging HLA-Cw*0602 consistently generate the most significant association signals in GWAS. However, it is unclear whether HLA-Cw*0602 is itself the causal PSORS1 allele, especially as the role of SNPs that may affect its expression has not been investigated. Here, we have undertaken an in-depth molecular characterization of the PSORS1 interval, with a view to identifying regulatory variants that may contribute to disease susceptibility. By analysing high-density SNP data, we refined PSORS1 to a 179 kb region encompassing HLA-C and the neighbouring HCG27 pseudogene. We compared multiple MHC sequences spanning this refined locus and identified 144 candidate susceptibility variants, which are unique to chromosomes bearing HLA-Cw*0602. In parallel, we investigated the epigenetic profile of the critical PSORS1 interval and uncovered three enhancer elements likely to be active in T lymphocytes. Finally we showed that nine candidate susceptibility SNPs map within a HLA-C enhancer and that three of these variants co-localise with binding sites for immune-related transcription factors. These data indicate that SNPs affecting HLA-Cw*0602 expression are likely to contribute to psoriasis susceptibility and highlight the importance of integrating multiple experimental approaches in the investigation of complex genomic regions such as the MHC. PMID:23990973

Increased carrier prevalence of deficient CYP2C9, CYP2C19 and CYP2D6 alleles in depressed patients referred to a tertiary psychiatric hospital.

PubMed

Ruaño, Gualberto; Villagra, David; Rahim, Umme Salma; Windemuth, Andreas; Kocherla, Mohan; Bower, Bruce; Szarek, Bonnie L; Goethe, John W

2008-11-01

This study compared the types and carrier prevalences of clinically significant DNA polymorphisms in the cytochrome P450 (CYP450) genes CYP2C9, CYP2C19 and CYP2D6 in major depressive disorder patients with a control group of nonpsychiatrically ill, medical outpatients. We conducted a case-control study using 73 psychiatric outpatients diagnosed with depression and referred to a tertiary center, The Institute of Living (Hartford, CT, USA), for treatment resistance or intolerable side-effects to psychotropic drugs. The controls were 120 cardiovascular patients from Hartford Hospital being treated for dyslipidemia but otherwise healthy and not psychiatrically ill. DNA typing to detect polymorphisms in the genes CYP2C9, CYP2C19 and CYP2D6 was accomplished with the Tag-It™ mutation detection assay and the Luminex xMAP ® system. The percentage of individuals in psychiatric versus control groups with two wild-type alleles for CYP2C9, CYP2C19 and CYP2D6 genes, were 50 versus 74% (p < 0.001), 71 versus 73% (not statistically significant) and 36 versus 43% (trend, p < 0.2), respectively. Within the psychiatric population, 57% of individuals were carriers of non-wild-type alleles for 2-3 genes, compared with 36% in the control population (p < 0.0001). The balance, 43% in the psychiatric population and 64% in the control, were carriers of non-wild-type alleles for none or one gene. These findings reveal that clinically relevant CYP2C9 polymorphisms occur more frequently in depressed psychiatric patients than in nonpsychiatric controls. The same trend was found for polymorphisms in the CYP2D6 gene. We found a significant cumulative metabolic deficiency in the psychiatric population for combinations of the CYP2C9, CYP2C19 and CYP2D6 genes. The significant enrichment of CYP2C9-deficient alleles in the psychiatric population validates a previously reported association of this gene with the risk for depression disorders. The high prevalence of carriers with deficient and null

Signatures of selection among sex-determining alleles of the honey bee.

PubMed

Hasselmann, Martin; Beye, Martin

2004-04-06

Patterns of DNA polymorphisms are a primary tool for dissecting signatures of selection; however, the underlying selective forces are poorly understood for most genes. A classical example of diversifying selection is the complementary sex-determining locus that is found in the very large insect order Hymenoptera (bees, wasps, ants, and sawflies). The gene responsible for sex determination, the complementary sex determiner (csd), has been most recently identified in the honey bee. Females are heterozygous at this locus. Males result when there is only one functional allele present, as a result of either homozygosity (fertilized eggs) or, more commonly, hemizygosity (unfertilized eggs). The homozygotes, diploid males, do not reproduce and have zero fitness, which implies positive selection in favor of rare alleles. Large differences in csd cDNA sequences within and between four populations were found that fall into two major groups, types I and II. Type I consists of several allelic lineages that were maintained over an extended period, an indication of balancing selection. Diversifying selection has operated on several confined parts of the protein, as shown by an excess of nonsynonymous differences. Elevated sequence differences indicate another selected part near a repeat region. These findings have general implications about the understanding of both the function of the multiallelic mechanism and the adaptive processes on the level of nucleotide sequences. Moreover, the first csd sequence data are a notable basis for the avoidance of diploid males in bee selection programs by allele-assisted breeding.

Effectiveness of Motivational Interviewing in improving lipid level in patients with dyslipidemia assisted by general practitioners: Dislip-EM study protocol.

PubMed

Pérula, Luis A; Bosch, Josep M; Bóveda, Julia; Campiñez, Manuel; Barragán, Nieves; Arboniés, Juan C; Prados, Jose A; Martín, Enrique; Martín, Remedios; Massons, Josep; Criado, Margarita; Ruiz, Roger; Fernández, José A; Buitrago, Francisco; Olaya, Inmaculada; Pérez, Modesto; Ruiz, Joaquin

2011-11-05

The non-pharmacological approach to cholesterol control in patients with hyperlipidemia is based on the promotion of a healthy diet and physical activity. Thus, to help patients change their habits, it is essential to identify the most effective approach. Many efforts have been devoted to explain changes in or adherence to specific health behaviors. Such efforts have resulted in the development of theories that have been applied in prevention campaigns, and that include brief advice and counseling services. Within this context, Motivational Interviewing has proven to be effective in changing health behaviors in specific cases. However, more robust evidence is needed on the effectiveness of Motivational Interviewing in treating chronic pathologies -such as dyslipidemia- in patients assisted by general practitioners. This article describes a protocol to assess the effectiveness of MI as compared with general practice (brief advice), with the aim of improving lipid level control in patients with dyslipidemia assisted by a general practitioner. An open, two-arm parallel, multicentre, cluster, controlled, randomized, clinical trial will be performed. A total of 48-50 general practitioners from 35 public primary care centers in Spain will be randomized and will recruit 436 patients with dyslipidemia. They will perform an intervention based either on Motivational Interviewing or on the usual brief advice. After an initial assessment, follow-ups will be performed at 2, 4, 8 and 12 months. Primary outcomes are lipid levels (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) and cardiovascular risk. The study will assess the degree of dietary and physical activity improvement, weight loss in overweight patients, and adherence to treatment guidelines. Motivational interview skills constitute the primary strategies GPs use to treat their patients. Having economical, simple, effective and applicable techniques is essential for primary care professionals to help

Effectiveness of Motivational Interviewing in improving lipid level in patients with dyslipidemia assisted by general practitioners: Dislip-EM study protocol

PubMed Central

2011-01-01

Background The non-pharmacological approach to cholesterol control in patients with hyperlipidemia is based on the promotion of a healthy diet and physical activity. Thus, to help patients change their habits, it is essential to identify the most effective approach. Many efforts have been devoted to explain changes in or adherence to specific health behaviors. Such efforts have resulted in the development of theories that have been applied in prevention campaigns, and that include brief advice and counseling services. Within this context, Motivational Interviewing has proven to be effective in changing health behaviors in specific cases. However, more robust evidence is needed on the effectiveness of Motivational Interviewing in treating chronic pathologies -such as dyslipidemia- in patients assisted by general practitioners. This article describes a protocol to assess the effectiveness of MI as compared with general practice (brief advice), with the aim of improving lipid level control in patients with dyslipidemia assisted by a general practitioner. Methods/Design An open, two-arm parallel, multicentre, cluster, controlled, randomized, clinical trial will be performed. A total of 48-50 general practitioners from 35 public primary care centers in Spain will be randomized and will recruit 436 patients with dyslipidemia. They will perform an intervention based either on Motivational Interviewing or on the usual brief advice. After an initial assessment, follow-ups will be performed at 2, 4, 8 and 12 months. Primary outcomes are lipid levels (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) and cardiovascular risk. The study will assess the degree of dietary and physical activity improvement, weight loss in overweight patients, and adherence to treatment guidelines. Discussion Motivational interview skills constitute the primary strategies GPs use to treat their patients. Having economical, simple, effective and applicable techniques is essential

ANGPTL3 is part of the machinery causing dyslipidemia majorily via LPL inhibition in mastitis mice.

PubMed

Xiao, Hong-Bo; Wang, Ji-Ying; Sun, Zhi-Liang

2017-12-01

Previous investigations have shown that inflammation induces changes in lipid and lipoprotein metabolism, and increased expression of angiopoietin-like protein 3 (ANGPTL3) contributes to the development of dyslipidemia. Here we investigated whether there is a correlation between increased ANGPTL3 expression and dyslipidemia in mastitis mice. Thirty mice were divided into two groups: control group and Staphylococcus aureus (S. aureus)-induced mastitis mice group. Changes in the levels of blood lipids [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)]; activity of myeloperoxidase (MPO); concentrations of plasma inflammation biomarkers [interferon-γ (IFNγ), tumor necrosis factor α (TNFα), and interleukin-1α (IL-1α)]; concentration of plasma ANGPTL3 protein; lipoprotein lipase (LPL) activities in postheparin plasma; expressions of hepatic N-acetylgalactosaminyltransferase 2 (GALNT2), hepatic ANGPTL3 and adipose LPL were determined. The major results indicated specific pathological mammary tissue changes, elevated MPO activity, reduced GALNT2 mRNA expression, elevated ANGPTL3 mRNA and protein expression and reduced LPL mRNA and protein expression. In plasma samples the S.aureus infused mice displayed elevated ANGPTL3 protein concentration, TG, TC and LDL-C levels, and reduced postheparin LPL activities and HDL-C level. The data suggests that ANGPTL3 is part of the machinery causing dyslipidemia majorily via LPL inhibition in mastitis mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Loss of LCAT activity in the golden Syrian hamster elicits pro-atherogenic dyslipidemia and enhanced atherosclerosis.

PubMed

Dong, Zhao; Shi, Haozhe; Zhao, Mingming; Zhang, Xin; Huang, Wei; Wang, Yuhui; Zheng, Lemin; Xian, Xunde; Liu, George

2018-06-01

Lecithin cholesterol acyltransferase (LCAT) plays a pivotal role in HDL metabolism but its influence on atherosclerosis remains controversial for decades both in animal and clinical studies. Because lack of cholesteryl ester transfer protein (CETP) is a major difference between murine and humans in lipoprotein metabolism, we aimed to create a novel Syrian Golden hamster model deficient in LCAT activity, which expresses endogenous CETP, to explore its metabolic features and particularly the influence of LCAT on the development of atherosclerosis. CRISPR/CAS9 gene editing system was employed to generate mutant LCAT hamsters. The characteristics of lipid metabolism and the development of atherosclerosis in the mutant hamsters were investigated using various conventional methods in comparison with wild type control animals. Hamsters lacking LCAT activity exhibited pro-atherogenic dyslipidemia as diminished high density lipoprotein (HDL) and ApoAI, hypertriglyceridemia, Chylomicron/VLDL accumulation and significantly increased ApoB100/48. Mechanistic study for hypertriglyceridemia revealed impaired LPL-mediated lipolysis and increased very low density lipoprotein (VLDL) secretion, with upregulation of hepatic genes involved in lipid synthesis and transport. The pro-atherogenic dyslipidemia in mutant hamsters was exacerbated after high fat diet feeding, ultimately leading to near a 3- and 5-fold increase in atherosclerotic lesions by aortic en face and sinus lesion quantitation, respectively. Our findings demonstrate that LCAT deficiency in hamsters develops pro-atherogenic dyslipidemia and promotes atherosclerotic lesion formation. Published by Elsevier Inc.

Allelic Expression of Deleterious Protein-Coding Variants across Human Tissues

PubMed Central

Kukurba, Kimberly R.; Zhang, Rui; Li, Xin; Smith, Kevin S.; Knowles, David A.; How Tan, Meng; Piskol, Robert; Lek, Monkol; Snyder, Michael; MacArthur, Daniel G.; Li, Jin Billy; Montgomery, Stephen B.

2014-01-01

Personal exome and genome sequencing provides access to loss-of-function and rare deleterious alleles whose interpretation is expected to provide insight into individual disease burden. However, for each allele, accurate interpretation of its effect will depend on both its penetrance and the trait's expressivity. In this regard, an important factor that can modify the effect of a pathogenic coding allele is its level of expression; a factor which itself characteristically changes across tissues. To better inform the degree to which pathogenic alleles can be modified by expression level across multiple tissues, we have conducted exome, RNA and deep, targeted allele-specific expression (ASE) sequencing in ten tissues obtained from a single individual. By combining such data, we report the impact of rare and common loss-of-function variants on allelic expression exposing stronger allelic bias for rare stop-gain variants and informing the extent to which rare deleterious coding alleles are consistently expressed across tissues. This study demonstrates the potential importance of transcriptome data to the interpretation of pathogenic protein-coding variants. PMID:24786518

Specific Silencing of L392V PSEN1 Mutant Allele by RNA Interference

PubMed Central

Sierant, Malgorzata; Paduszynska, Alina; Kazmierczak-Baranska, Julia; Nacmias, Benedetta; Sorbi, Sandro; Bagnoli, Silvia; Sochacka, Elzbieta; Nawrot, Barbara

2011-01-01

RNA interference (RNAi) technology provides a powerful molecular tool to reduce an expression of selected genes in eukaryotic cells. Short interfering RNAs (siRNAs) are the effector molecules that trigger RNAi. Here, we describe siRNAs that discriminate between the wild type and mutant (1174 C→G) alleles of human Presenilin1 gene (PSEN1). This mutation, resulting in L392V PSEN1 variant, contributes to early onset familial Alzheimer's disease. Using the dual fluorescence assay, flow cytometry and fluorescent microscopy we identified positions 8th–11th, within the central part of the antisense strand, as the most sensitive to mismatches. 2-Thiouridine chemical modification introduced at the 3′-end of the antisense strand improved the allele discrimination, but wobble base pairing adjacent to the mutation site abolished the siRNA activity. Our data indicate that siRNAs can be designed to discriminate between the wild type and mutant alleles of genes that differ by just a single nucleotide. PMID:21559198

Loss of RNA expression and allele-specific expression associated with congenital heart disease

PubMed Central

McKean, David M.; Homsy, Jason; Wakimoto, Hiroko; Patel, Neil; Gorham, Joshua; DePalma, Steven R.; Ware, James S.; Zaidi, Samir; Ma, Wenji; Patel, Nihir; Lifton, Richard P.; Chung, Wendy K.; Kim, Richard; Shen, Yufeng; Brueckner, Martina; Goldmuntz, Elizabeth; Sharp, Andrew J.; Seidman, Christine E.; Gelb, Bruce D.; Seidman, J. G.

2016-01-01

Congenital heart disease (CHD), a prevalent birth defect occurring in 1% of newborns, likely results from aberrant expression of cardiac developmental genes. Mutations in a variety of cardiac transcription factors, developmental signalling molecules and molecules that modify chromatin cause at least 20% of disease, but most CHD remains unexplained. We employ RNAseq analyses to assess allele-specific expression (ASE) and biallelic loss-of-expression (LOE) in 172 tissue samples from 144 surgically repaired CHD subjects. Here we show that only 5% of known imprinted genes with paternal allele silencing are monoallelic versus 56% with paternal allele expression—this cardiac-specific phenomenon seems unrelated to CHD. Further, compared with control subjects, CHD subjects have a significant burden of both LOE genes and ASE events associated with altered gene expression. These studies identify FGFBP2, LBH, RBFOX2, SGSM1 and ZBTB16 as candidate CHD genes because of significantly altered transcriptional expression. PMID:27670201

Variant ribosomal RNA alleles are conserved and exhibit tissue-specific expression

PubMed Central

Parks, Matthew M.; Kurylo, Chad M.; Dass, Randall A.; Bojmar, Linda; Lyden, David; Vincent, C. Theresa; Blanchard, Scott C.

2018-01-01

The ribosome, the integration point for protein synthesis in the cell, is conventionally considered a homogeneous molecular assembly that only passively contributes to gene expression. Yet, epigenetic features of the ribosomal DNA (rDNA) operon and changes in the ribosome’s molecular composition have been associated with disease phenotypes, suggesting that the ribosome itself may possess inherent regulatory capacity. Analyzing whole-genome sequencing data from the 1000 Genomes Project and the Mouse Genomes Project, we find that rDNA copy number varies widely across individuals, and we identify pervasive intra- and interindividual nucleotide variation in the 5S, 5.8S, 18S, and 28S ribosomal RNA (rRNA) genes of both human and mouse. Conserved rRNA sequence heterogeneities map to functional centers of the assembled ribosome, variant rRNA alleles exhibit tissue-specific expression, and ribosomes bearing variant rRNA alleles are present in the actively translating ribosome pool. These findings provide a critical framework for exploring the possibility that the expression of genomically encoded variant rRNA alleles gives rise to physically and functionally heterogeneous ribosomes that contribute to mammalian physiology and human disease. PMID:29503865

Characterization of the treefrog null allele, 1991

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guttman, S.I.

1992-04-01

Spring peeper (Hyla crucifer) tadpoles collected from the waste storage area during the Biological and Ecological Site Characterization of the Feed Materials Production Center (FEMP) in 1986 and 1987 appeared to be unique. A null (inactive) allele was found at the glucose phosphate isomerase enzyme locus in significant frequencies (approximately 20%) each year; this allele did not appear to occur in the offsite sample collected approximately 15km from the FEMP. Null alleles at this locus have not been reported in other amphibian populations; when they have been found in other organisms they have invariably been lethal in the homozygous condition.

Prevalence and risk factors associated with the metabolic syndrome and dyslipidemia in White, Black, Amerindian and Mixed Hispanics in Zulia State, Venezuela.

PubMed

Florez, Hermes; Silva, Eglé; Fernández, Virginia; Ryder, Elena; Sulbarán, Tulio; Campos, Gilberto; Calmón, Gustavo; Clavel, Emilio; Castillo-Florez, Sumaya; Goldberg, Ronald

2005-07-01

Studies have highlighted the association between insulin resistance (IR) and several cardiovascular (CV) risk factors, including hypertension (HTN), obesity, dyslipidemia (i.e. high triglyceride and low HDL-cholesterol) and glucose intolerance, in a cluster known as the metabolic syndrome (MS). There are few data on the frequency of the MS and dyslipidemia in developing countries, and none in South America. To estimate the prevalence of the MS and its components in Zulia State, Venezuela, and to establish associated demographic and clinical factors, we evaluated 3108 Hispanic men and women aged 20 years or older from a cross-sectional survey of a random representative sample from each health district in Zulia State, Venezuela (1999-2001). Prevalence of the MS and dyslipidemia was defined according to the National Cholesterol Education Program (NCEP)/Adult Treatment Panel III (ATP III) criteria. The age-adjusted prevalence of MS and dyslipidemia was 31.2% and 24.1%, respectively, with higher rates in men than in women. Prevalence rates increased with age and with the degree of obesity. MS prevalence was lower in Amerindian (17.%) compared to Black (27.2%), White (33.3%) and Mixed (37.4%) men, but no differences were found among women. Overall, low HDL-cholesterol (65.3%), abdominal obesity (42.9%) and HTN (38.1%) were the most frequent MS components. After adjusting for age, sex and race groups, family history of diabetes, obesity and HTN were associated with the MS. Sedentary lifestyle also increased the risk of MS, event after adjusting for the same covariates, obesity and the degree of IR. These results suggest that MS is found in approximately one-third of the Venezuelan adult population in Zulia State, with higher prevalence in men related to the presence of dyslipidemia. Lifestyle interventions in MS subjects are needed in Venezuela to halt the burden of CV disease and diabetes.

Modeling the influence of APOC3, APOE, and TNF polymorphisms on the risk of antiretroviral therapy-associated lipid disorders.

PubMed

Tarr, Philip E; Taffé, Patrick; Bleiber, Gabriela; Furrer, Hansjakob; Rotger, Margalida; Martinez, Raquel; Hirschel, Bernard; Battegay, Manuel; Weber, Rainer; Vernazza, Pietro; Bernasconi, Enos; Darioli, Roger; Rickenbach, Martin; Ledergerber, Bruno; Telenti, Amalio

2005-05-01

Single-nucleotide polymorphisms in genes involved in lipoprotein and adipocyte metabolism may explain why dyslipidemia and lipoatrophy occur in some but not all antiretroviral therapy (ART)-treated individuals. We evaluated the contribution of APOC3 -482C-->T, -455T-->C, and 3238C-->G; epsilon 2 and epsilon 4 alleles of APOE; and TNF -238G-->A to dyslipidemia and lipoatrophy by longitudinally modeling >2600 lipid determinations and 2328 lipoatrophy assessments in 329 ART-treated patients during a median follow-up period of 3.4 years. In human immunodeficiency virus (HIV)-infected individuals, the effects of variant alleles of APOE on plasma cholesterol and triglyceride levels and of APOC3 on plasma triglyceride levels were comparable to those reported in the general population. However, when treated with ritonavir, individuals with unfavorable genotypes of APOC3 and [corrected] APOE were at risk of extreme hypertriglyceridemia. They had median plasma triglyceride levels of 7.33 mmol/L, compared with 3.08 mmol/L in the absence of ART. The net effect of the APOE*APOC3*ritonavir interaction was an increase in plasma triglyceride levels of 2.23 mmol/L. No association between TNF -238G-->A and lipoatrophy was observed. Variant alleles of APOE and APOC3 contribute to an unfavorable lipid profile in patients with HIV. Interactions between genotypes and ART can lead to severe hyperlipidemia. Genetic analysis may identify patients at high risk for severe ritonavir-associated hypertriglyceridemia.

Allele frequency data for 15 autosomal STR loci in eight Indonesian subpopulations.

PubMed

Venables, Samantha J; Daniel, Runa; Sarre, Stephen D; Soedarsono, Nurtami; Sudoyo, Herawati; Suryadi, Helena; van Oorschot, Roland A H; Walsh, Simon J; Widodo, Putut T; McNevin, Dennis

2016-01-01

Evolutionary and cultural history can affect the genetic characteristics of a population and influences the frequency of different variants at a particular genetic marker (allele frequency). These characteristics directly influence the strength of forensic DNA evidence and make the availability of suitable allele frequency information for every discrete country or jurisdiction highly relevant. Population sub-structure within Indonesia has not been well characterised but should be expected given the complex geographical, linguistic and cultural architecture of the Indonesian population. Here we use forensic short tandem repeat (STR) markers to identify a number of distinct genetic subpopulations within Indonesia and calculate appropriate population sub-structure correction factors. This data represents the most comprehensive investigation of population sub-structure within Indonesia to date using these markers. The results demonstrate that significant sub-structure is present within the Indonesian population and must be accounted for using island specific allele frequencies and corresponding sub-structure correction factors in the calculation of forensic DNA match statistics. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Protective effect of Trigonella foenum-graecum Linn. on monosodium glutamate-induced dyslipidemia and oxidative stress in rats

PubMed Central

Kumar, Parveen; Bhandari, Uma

2013-01-01

Objectives: The present study was designed to evaluate the effect of aqueous extract of Trigonella foenum-graecum(AqE-TFG) seeds on monosodium glutamate (MSG)-induced dyslipidemia and oxidative stress in Wistar rats. Materials and Methods: Neonatal Wistar rats were treated subcutaneously with MSG (4 g/kg b.w.) from day 2 to 14 after birth, on alternate days. After attaining six-weeks of age, MSG-treated rats were administered with AqE-TFG (0.5 and 1 g/kg b.w., orally) or orlistat (10 mg/kg b.w., orally) for 28 days, respectively. Serum chemistry and relevant enzymes in hepato-cardiac tissues were assessed on day 29. Results: AqE-TFG produced significant reduction in serum total cholesterol (TC), triglycerides (TGs), lactate dehydrogenase (LDH), aspartate amino transferase (AST), alanine amino transferase (ALT), hepatic and cardiac lipid peroxides (MDA) levels and elevation in serum high density lipoprotein cholesterol (HDL-C), hepatic and cardiac antioxidant enzymes [glutathione (GSH), and superoxide dismutase (SOD) and catalase (CAT)] levels. Conclusion: Results were comparable with orlistat, a standard anti-obesity drug, and provide clear evidence that the AqE-TFG treatment offered significant protection against MSG-induced dyslipidemia and oxidative stress, and may play an important role in amelioration of the free radical generated consequences like dyslipidemia and atherosclerosis. PMID:23716888

A survey of the incidence of dyslipidemia and its components in people over 20 years old in Ahvaz: A cohort study 2009-2014.

PubMed

Latifi, S M; Karandish, M; Shahbazian, H B; Chinipardaz, R; Sabet, A; Pirani, N

2017-12-01

Dyslipidemia is one of the major risk factors for atherosclerosis and the main cause of death in the developing and developed countries. In this cohort study, the incidence of dyslipidemia and its components have been studied among individuals over 20 years old in Ahvaz, southwest of Iran. The Phase 1 of this study was conducted on the prevalence of Metabolic syndrome and its related factors by Diabetes Research Center in 2009. The target population included individuals over 20 years old who were selected using cluster sampling in Ahvaz health centers. In the second phase of the study, 5 years later in 2014, subjects were again recalled by health centers. Questionnaires, anthropometric indices and measurements were repeated similar to Phase 1. The blood sample was taken from everyone after 12h of fasting and then the factors (Chol, TG, HDL) were measured. The cumulative incidence of dyslipidemia obtained 60.7% (males 56.7% and females 64.8%). lipid profile {HDL, Triglycerides and Cholesterol had changes in their means(a significant reduction in the mean about 10, 22.25 and 13 units respectively) between baseline and 5 years later. Waist circumference here associated with incidence of high LDL and high chol, also sex and High LDL 'educational level and daily consumption of vegetables were associated with incidence of low HDL and dyslipidemia respectively. Age, educational level and daily intake of fruits and vegetables were effective variables on incidence of dyslipidemia. According to various studies, LDL and HDL levels in different regions of Iran, seems to be influenced by factors such as climate, nutrition and activity levels. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

A natural allele of Nxf1/TAP supresses retrovirus insertional mutations

PubMed Central

Floyd, Jennifer A.; Gold, David A.; Concepcion, Dorothy; Poon, Tiffany H.; Wang, Xiaobo; Keithley, Elizabeth; Chen, Dan; Ward, Erica J.; Chinn, Steven B.; Friedman, Rick A.; Yu, Hon-Tsen; Moriwaki, Kazuo; Shiroishi, Toshihiko; Hamilton, Bruce A.

2009-01-01

Endogenous retroviruses have shaped the evolution of mammalian genomes. Host genes that control the effects of retrovirus insertions are therefore of great interest. The Modifier-of-vibrator-1 locus controls level of correctly processed mRNA from genes mutated by endogenous retrovirus insertions into introns, including the pitpnvb tremor mutation and the Eya1BOR model of human branchiootorenal syndrome. Positional complementation cloning identifies Mvb1 as the nuclear export factor Nxf1, providing an unexpected link between mRNA export receptor and pre-mRNA processing. Population structure of the suppressing allele in wild M. m. castaneus suggests selective advantage. A congenic Mvb1CAST allele is a useful tool for modifying gene expression from existing mutations and could be used to manipulate engineered mutations containing retroviral elements. PMID:14517553

Apolipoprotein E alleles in Alzheimer`s and Parkinson`s patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poduslo, S.E.; Schwankhaus, J.D.

1994-09-01

A number of investigators have found an association between the apolipoprotein E4 allele and Alzheimer`s disease. The E4 allele appears at a higher frequency in late onset familial Alzheimer`s patients. In our studies we obtained blood samples from early and late onset familial and sporadic Alzheimer`s patients and spouses, as well as from Parkinson`s patients. The patients were diagnosed as probable Alzheimer`s patients after a neurological examination, extensive blood work, and a CAT scan. The diagnosis was made according to the NINCDS-ADRDA criteria. The apolipoprotein E4 polymorphism was detected after PCR amplification of genomic DNA, restriction enzyme digestion with Hhal,more » and polyacrylamide gel electrophoresis. Ethidium bromide-stained bands at 91 bp were designated as allele 3, at 83 bp as allele 2, and at 72 bp as allele 4. Of the 84 probable Alzheimer`s patients (all of whom were Caucasian), 47 were heterozygous and 13 were homozygous for the E4 allele. There were 26 early onset patients; 13 were heterozygous and 7 homozygous for the E4 allele. The frequencies for the E4 allele for late onset familial patients was 0.45 and for sporadic patients was 0.37. We analyzed 77 spouses with an average age of 71.9 {plus_minus} 7.4 years as controls, and 15 were heterozygous for the E4 allele for an E4 frequency of 0.097. Of the 53 Parkinson`s patients, 11 had the E4 allele for a frequency of 0.113. Thus our findings support the association of the ApoE4 allele with Alzheimer`s disease.« less

Cattle with the BoLA class II DRB3*0902 allele have significantly lower bovine leukemia proviral loads.

PubMed

Hayashi, Takumi; Mekata, Hirohisa; Sekiguchi, Satoshi; Kirino, Yumi; Mitoma, Shuya; Honkawa, Kazuyuki; Horii, Yoichiro; Norimine, Junzo

2017-09-12

The bovine MHC (BoLA) class II DRB3 alleles are associated with polyclonal expansion of lymphocytes caused by bovine leukemia virus (BLV) infection in cattle. To examine whether the DRB3*0902 allele, one of the resistance-associated alleles, is associated with the proviral load, we measured BLV proviral load of BLV-infected cattle and clarified their DRB3 alleles. Fifty-seven animals with DRB3*0902 were identified out of 835 BLV-infected cattle and had significantly lower proviral load (P<0.000001) compared with the rest of the infected animals, in both Japanese Black and Holstein cattle. This result strongly indicates that the BoLA class II DRA/DRB3*0902 molecule plays an important immunological role in suppressing viral replication, resulting in resistance to the disease progression.

Grape Consumption Increases Anti-Inflammatory Markers and Upregulates Peripheral Nitric Oxide Synthase in the Absence of Dyslipidemias in Men with Metabolic Syndrome

PubMed Central

Barona, Jacqueline; Blesso, Christopher N.; Andersen, Catherine J.; Park, Youngki; Lee, Jiyoung; Fernandez, Maria Luz

2012-01-01

We evaluated the effects of grape consumption on inflammation and oxidation in the presence or absence of dyslipidemias in metabolic syndrome (MetS). Men with MetS (n = 24), 11 with high triglycerides and low HDL and 13 with no dyslipidemia were recruited and randomly allocated to consume daily either 46 g of lyophilized grape powder (GRAPE), equivalent to 252 g fresh grapes, or placebo with an identical macronutrient composition and caloric value as GRAPE for four weeks. After a three-week washout, participants followed the alternate treatment. We measured changes between placebo and GRAPE periods in inflammatory and oxidative stress markers both in circulation and in gene expression. Changes in plasma adiponectin (p < 0.05), interleukin (IL)-10 (p < 0.005) and in mRNA expression of the inducible isoform of nitric oxide synthase (iNOS) (p < 0.25) were increased in the GRAPE compared to the placebo period only in those individuals without dyslipidemia. Additionally, plasma IL-10 was negatively correlated with NOX2 expression, a marker of oxidative stress (r = −0.55, p < 0.01), while iNOS expression was positively correlated with the expression of superoxide dismutase 2 (r = 0.642, p < 0.01), a key anti-oxidative enzyme. Grape consumption displayed anti-oxidative and increased anti-inflammatory markers in the absence of the inflammatory milieu associated with dyslipidemias. PMID:23222963

[LDL-cholesterol control in patients with genetic dyslipidemia followed up by Lipid and Vascular Risk Units of the Spanish Society of Arteriosclerosis].

PubMed

Lahoz, Carlos; Mostaza, José María; Pintó, Xavier; de la Cruz, Juan José; Banegas, José Ramón; Pedro-Botet, Juan

2015-01-01

To evaluate low-density lipoprotein-cholesterol (LDLc) achieved in patients with genetic dyslipidemia treated during one year in Lipid and Vascular Risk Units (LVRU) of the Spanish Society of Arteriosclerosis (SSA). Observational, longitudinal, retrospective, multicenter national study that included consecutive patients of both sexes over 18 years of age referred due to dyslipidemia to LVRU of the SSA. Information was collected from medical records corresponding to two visits in the lipid unit. A total of 527 patients (mean age 48 years, 60.0% men) diagnosed with genetic dyslipidemia (241 with heterozygous familial hypercholesterolemia, and 286 with familial combined hyperlipidemia) were included. The mean follow-up was 12.9 months. In the last visit, 94% were taking statins, one third combined with ezetimibe, although only 41% were taking a high-intensity hypolipidemic treatment. Overall, 28.5% of patients attained an LDLc level<100 mg/dL, 35.8% decreased their LDLc by >50%, and 53.8% achieved one of the two. Predictors of target LDLc levels in the multivariate analysis were age, smoking habit and the presence of vascular disease. Over half of the patients with genetic dyslipidemia followed up by LVRU of SSA achieve LDLc objectives after one year of follow-up. The use of high-intensity hypolipidemic treatment could improve these results. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

Involvement of toll-like receptor 2 and 4 in association between dyslipidemia and osteoclast differentiation in apolipoprotein E deficient rat periodontium

PubMed Central

2013-01-01

Background Dyslipidemia increases circulating levels of oxidized low-density lipoprotein (OxLDL) and this may induce alveolar bone loss through toll-like receptor (TLR) 2 and 4. The purpose of this study was to investigate the effects of dyslipidemia on osteoclast differentiation associated with TLR2 and TLR4 in periodontal tissues using a rat dyslipidemia (apolipoprotein E deficient) model. Methods Levels of plasma OxLDL, and the cholesterol and phospholipid profiles in plasma lipoproteins were compared between apolipoprotein E-deficient rats (16-week-old males) and wild-type (control) rats. In the periodontal tissue, we evaluated the changes in TLR2, TLR4, receptor activator of nuclear factor kappa B ligand (RANKL) and tartrate resistant acid phosphatase (TRAP) expression. Results Apolipoprotein E-deficient rats showed higher plasma levels of OxLDL than control rats (p<0.05), with higher plasma levels of total cholesterol (p<0.05) and LDL-cholesterol (p<0.05) and lower plasma levels of high-density lipoprotein cholesterol (p<0.05). Their periodontal tissue also exhibited a higher ratio of RANKL-positive cells and a higher number of TRAP-positive osteoclasts than control rats (p<0.05). Furthermore, periodontal gene expression of TLR2, TLR4 and RANKL was higher in apolipoprotein E-deficient rats than in control rats (p<0.05). Conclusion These findings underscore the important role for TLR2 and TLR4 in mediating the osteoclast differentiation on alveolar bone response to dyslipidemia. PMID:23295061

The effect and safety of anacetrapib in the treatment of dyslipidemia: a systematic review and meta-analysis.

PubMed

Zhou, Junteng; Zhang, Qi; Wang, Yushu; Gao, Peijuan; Chen, Decai

2018-01-01

Cardiovascular disease (CVD) is the major cause of morbidity and mortality worldwide. Anacetrapib may be a new treatment option that has a cardiovascular benefit for the management of dyslipidemia. The aim of our current study was to perform a systematic review and meta-analysis of all randomized controlled trials (RCTs) assessing the effect and safety of anacetrapib in the treatment of dyslipidemia. We systematically searched PubMed, Embase, and Cochrane Library database from their inception to 5 October 2017, with the terms: 'anacetrapib' and 'placebo'. From 287 initial citations, 10 studies including 34781 patients with dyslipidemia were included in the final systematic review and meta-analysis. Pooled results showed that anacetrapib significantly increased high density lipoprotein cholesterol (HDL-C) [weighted mean differences (WMD) 53.07, 95% confidence interval (95% CI) 46.79 to 59.36] and apolipoprotein AI (ApoAI) (WMD 53.44, 95% CI 45.72 to 61.16). Our study also showed that anacetrapib significantly reduced low density lipoprotein cholesterol (LDL-C) (WMD -32.99; 95% CI -37.13 to -28.86), Non-HDL-C (WMD -39.19; 95% CI -52.22 to -26.16), triglycerides (TG) (WMD -9.97; 95% CI -10.54 to -9.41), apolipoprotein B (ApoB) (WMD -22.55; 95% CI -28.56 to -16.54) and lipoprotein a [LP(a)] (WMD -13.35; 95% CI -18.31 to -8.39). Our results demonstrated that there was no significant difference in all the following adverse events between the anacetrapib group and placebo group: [hepato-toxicity (OR 0.90, 95% CI: 0.75 to 1.07); musculoskeletal injury (OR 1.01, 95% CI: 0.88 to 1.15); drug-related adverse event (OR 1.00, 95% CI: 0.96 to 1.05); drug-related withdrawn (OR 1.01, 95% CI: 0.95 to 1.08)]. Although further studies are needed, our findings clearly offer support to the use of anacetrapib in the clinical management of patients with dyslipidemia.

Erasure and reestablishment of random allelic expression imbalance after epigenetic reprogramming

PubMed Central

Jeffries, Aaron Richard; Uwanogho, Dafe Aghogho; Cocks, Graham; Perfect, Leo William; Dempster, Emma; Mill, Jonathan; Price, Jack

2016-01-01

Clonal level random allelic expression imbalance and random monoallelic expression provides cellular heterogeneity within tissues by modulating allelic dosage. Although such expression patterns have been observed in multiple cell types, little is known about when in development these stochastic allelic choices are made. We examine allelic expression patterns in human neural progenitor cells before and after epigenetic reprogramming to induced pluripotency, observing that loci previously characterized by random allelic expression imbalance (0.63% of expressed genes) are generally reset to a biallelic state in induced pluripotent stem cells (iPSCs). We subsequently neuralized the iPSCs and profiled isolated clonal neural stem cells, observing that significant random allelic expression imbalance is reestablished at 0.65% of expressed genes, including novel loci not found to show allelic expression imbalance in the original parental neural progenitor cells. Allelic expression imbalance was associated with altered DNA methylation across promoter regulatory regions, with clones characterized by skewed allelic expression being hypermethylated compared to their biallelic sister clones. Our results suggest that random allelic expression imbalance is established during lineage commitment and is associated with increased DNA methylation at the gene promoter. PMID:27539784

Dyslipidemia and reference values for fasting plasma lipid concentrations in Danish/North-European White children and adolescents.

PubMed

Nielsen, Tenna Ruest Haarmark; Lausten-Thomsen, Ulrik; Fonvig, Cilius Esmann; Bøjsøe, Christine; Pedersen, Lise; Bratholm, Palle Skov; Hansen, Torben; Pedersen, Oluf; Holm, Jens-Christian

2017-04-28

Dyslipidemia is reported in 27 - 43% of children and adolescents with overweight/obesity and tracks into adulthood, increasing the risk of cardiovascular morbidity. Cut-off values for fasting plasma lipid concentrations are typically set at fixed levels throughout childhood. The objective of this cross-sectional study was to generate fasting plasma lipid references for a Danish/North-European White population-based cohort of children and adolescents, and investigate the prevalence of dyslipidemia in this cohort as well as in a cohort with overweight/obesity. A population-based cohort of 2141 (1275 girls) children and adolescents aged 6 - 19 (median 11.5) years was recruited from 11 municipalities in Denmark. Additionally, a cohort of children and adolescents of 1421 (774 girls) with overweight/obesity aged 6 - 19 years (median 11.8) was recruited for the study. Height, weight, and fasting plasma lipid concentrations were measured on all participants. Smoothed reference curves and percentiles were generated using the Generalized Additive Models for Location Scale and Shape package in the statistical software R. In the population-based cohort, plasma concentrations of total cholesterol (TC) (P < 0.05), low-density lipoprotein cholesterol (LDL) (P < 0.005), and high-density lipoprotein cholesterol (HDL) (P < 0.005) were higher in the youngest compared to the oldest tertile. Fasting plasma levels of triglycerides (TG) (P < 0.005) increased with age in both sexes. In boys, non-HDL was lower in the oldest compared to the youngest tertile (P < 0.0005). Concentrations of TC, LDL, non-HDL, and TG were higher (P < 0.05), and HDL lower (P < 0.05) in the cohort with overweight/obesity in both sexes and for all ages except for TC in the youngest girls. The overall prevalence of dyslipidemia was 6.4% in the population-based cohort and 28.0% in the cohort with overweight/obesity. The odds ratio for exhibiting dyslipidemia in the cohort with overweight

Sequence of a new DR12 allele with two silent mutations that affect PCR-SSP typing.

PubMed

Zanone, R; Bettens, F; Tiercy, J-M

2002-02-01

A new HLA-DR12 allele has been identified in a European Caucasoid bone marrow donor. The DRB1*12012 allele differs from DRB1*12011 by two silent substitutions at codons 72 and 78, two polymorphic positions used for DNA subtyping of the DR12 serotype. The co-occurence of the two nucleotide changes is unique to the DR12 group and results in a new PCR-SSP typing pattern. The complete HLA type of the donor is A24, A68; B55, B61; Cw*01, Cw*0304; DRB1*12012, DRB1*1402; DRB3*0101, DRB3*0202; DQB1*0301. HLA-DRB1*12012 is a rare allele as it occurs in < 0.2% of DR12 donors.

[Characteristics of dyslipidemia in cancer patients].

PubMed

Ostroumova, M N; Kovalenko, I G; Bershteĭn, L M; Tsyrlina, E V; Dil'man, V M

1986-01-01

Blood concentrations of total cholesterol, cholesterol of very high density lipoproteins (alpha-cholesterol), triglycerides, beta-lipoproteins and 11-hydroxycorticosteroids were studied in 560 patients with rectal, colon, lung, ovarian, breast and endometrial cancer as well as in 238 controls. Patients with breast and rectal cancer were examined before and repeatedly after operation (every 6-12 months within 4-5 years). The blood concentration of total cholesterol was found to be elevated in breast cancer patients and controls with fibroadenomatosis and decreased in females with ovarian cancer and males with lung cancer. The level of blood alpha-cholesterol was decreased in males with all tumor localizations under study and in females with ovarian and rectal cancer. The concentration of triglycerides was increased in women patients only. Three possible causes of dyslipidemia in cancer patients are discussed: its development before tumor manifestation, the effect of tumor on the metabolic status of the host and the role of emotional stress in the increase of triglycerides level in the blood of primary cancer patients.

Genetic exchange of fimbrial alleles exemplifies the adaptive virulence strategy of Porphyromonas gingivalis.

PubMed

Kerr, Jennifer E; Abramian, Jared R; Dao, Doan-Hieu V; Rigney, Todd W; Fritz, Jamie; Pham, Tan; Gay, Isabel; Parthasarathy, Kavitha; Wang, Bing-yan; Zhang, Wenjian; Tribble, Gena D

2014-01-01

Porphyromonas gingivalis is a gram-negative anaerobic bacterium, a member of the human oral microbiome, and a proposed "keystone" pathogen in the development of chronic periodontitis, an inflammatory disease of the gingiva. P. gingivalis is a genetically diverse species, and is able to exchange chromosomal DNA between strains by natural competence and conjugation. In this study, we investigate the role of horizontal DNA transfer as an adaptive process to modify behavior, using the major fimbriae as our model system, due to their critical role in mediating interactions with the host environment. We show that P. gingivalis is able to exchange fimbrial allele types I and IV into four distinct strain backgrounds via natural competence. In all recombinants, we detected a complete exchange of the entire fimA allele, and the rate of exchange varies between the different strain backgrounds. In addition, gene exchange within other regions of the fimbrial genetic locus was identified. To measure the biological implications of these allele swaps we compared three genotypes of fimA in an isogenic background, strain ATCC 33277. We demonstrate that exchange of fimbrial allele type results in profound phenotypic changes, including the quantity of fimbriae elaborated, membrane blebbing, auto-aggregation and other virulence-associated phenotypes. Replacement of the type I allele with either the type III or IV allele resulted in increased invasion of gingival fibroblast cells relative to the isogenic parent strain. While genetic variability is known to impact host-microbiome interactions, this is the first study to quantitatively assess the adaptive effect of exchanging genes within the pan genome cloud. This is significant as it presents a potential mechanism by which opportunistic pathogens may acquire the traits necessary to modify host-microbial interactions.

Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots.

PubMed

Baker, Christopher L; Petkova, Pavlina; Walker, Michael; Flachs, Petr; Mihola, Ondrej; Trachtulec, Zdenek; Petkov, Petko M; Paigen, Kenneth

2015-09-01

Genetic recombination during meiosis functions to increase genetic diversity, promotes elimination of deleterious alleles, and helps assure proper segregation of chromatids. Mammalian recombination events are concentrated at specialized sites, termed hotspots, whose locations are determined by PRDM9, a zinc finger DNA-binding histone methyltransferase. Prdm9 is highly polymorphic with most alleles activating their own set of hotspots. In populations exhibiting high frequencies of heterozygosity, questions remain about the influences different alleles have in heterozygous individuals where the two variant forms of PRDM9 typically do not activate equivalent populations of hotspots. We now find that, in addition to activating its own hotspots, the presence of one Prdm9 allele can modify the activity of hotspots activated by the other allele. PRDM9 function is also dosage sensitive; Prdm9+/- heterozygous null mice have reduced numbers and less active hotspots and increased numbers of aberrant germ cells. In mice carrying two Prdm9 alleles, there is allelic competition; the stronger Prdm9 allele can partially or entirely suppress chromatin modification and recombination at hotspots of the weaker allele. In cell cultures, PRDM9 protein variants form functional heteromeric complexes which can bind hotspots sequences. When a heteromeric complex binds at a hotspot of one PRDM9 variant, the other PRDM9 variant, which would otherwise not bind, can still methylate hotspot nucleosomes. We propose that in heterozygous individuals the underlying molecular mechanism of allelic suppression results from formation of PRDM9 heteromers, where the DNA binding activity of one protein variant dominantly directs recombination initiation towards its own hotspots, effectively titrating down recombination by the other protein variant. In natural populations with many heterozygous individuals, allelic competition will influence the recombination landscape.

Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots

PubMed Central

Baker, Christopher L.; Petkova, Pavlina; Walker, Michael; Flachs, Petr; Mihola, Ondrej; Trachtulec, Zdenek; Petkov, Petko M.; Paigen, Kenneth

2015-01-01

Genetic recombination during meiosis functions to increase genetic diversity, promotes elimination of deleterious alleles, and helps assure proper segregation of chromatids. Mammalian recombination events are concentrated at specialized sites, termed hotspots, whose locations are determined by PRDM9, a zinc finger DNA-binding histone methyltransferase. Prdm9 is highly polymorphic with most alleles activating their own set of hotspots. In populations exhibiting high frequencies of heterozygosity, questions remain about the influences different alleles have in heterozygous individuals where the two variant forms of PRDM9 typically do not activate equivalent populations of hotspots. We now find that, in addition to activating its own hotspots, the presence of one Prdm9 allele can modify the activity of hotspots activated by the other allele. PRDM9 function is also dosage sensitive; Prdm9 +/- heterozygous null mice have reduced numbers and less active hotspots and increased numbers of aberrant germ cells. In mice carrying two Prdm9 alleles, there is allelic competition; the stronger Prdm9 allele can partially or entirely suppress chromatin modification and recombination at hotspots of the weaker allele. In cell cultures, PRDM9 protein variants form functional heteromeric complexes which can bind hotspots sequences. When a heteromeric complex binds at a hotspot of one PRDM9 variant, the other PRDM9 variant, which would otherwise not bind, can still methylate hotspot nucleosomes. We propose that in heterozygous individuals the underlying molecular mechanism of allelic suppression results from formation of PRDM9 heteromers, where the DNA binding activity of one protein variant dominantly directs recombination initiation towards its own hotspots, effectively titrating down recombination by the other protein variant. In natural populations with many heterozygous individuals, allelic competition will influence the recombination landscape. PMID:26368021

Allelic Imbalance Is a Prevalent and Tissue-Specific Feature of the Mouse Transcriptome

PubMed Central

Pinter, Stefan F.; Colognori, David; Beliveau, Brian J.; Sadreyev, Ruslan I.; Payer, Bernhard; Yildirim, Eda; Wu, Chao-ting; Lee, Jeannie T.

2015-01-01

In mammals, several classes of monoallelic genes have been identified, including those subject to X-chromosome inactivation (XCI), genomic imprinting, and random monoallelic expression (RMAE). However, the extent to which these epigenetic phenomena are influenced by underlying genetic variation is unknown. Here we perform a systematic classification of allelic imbalance in mouse hybrids derived from reciprocal crosses of divergent strains. We observe that deviation from balanced biallelic expression is common, occurring in ∼20% of the mouse transcriptome in a given tissue. Allelic imbalance attributed to genotypic variation is by far the most prevalent class and typically is tissue-specific. However, some genotype-based imbalance is maintained across tissues and is associated with greater genetic variation, especially in 5′ and 3′ termini of transcripts. We further identify novel random monoallelic and imprinted genes and find that genotype can modify penetrance of parental origin even in the setting of large imprinted regions. Examination of nascent transcripts in single cells from inbred parental strains reveals that genes showing genotype-based imbalance in hybrids can also exhibit monoallelic expression in isogenic backgrounds. This surprising observation may suggest a competition between alleles and/or reflect the combined impact of cis- and trans-acting variation on expression of a given gene. Our findings provide novel insights into gene regulation and may be relevant to human genetic variation and disease. PMID:25858912

Role of the B Allele of Influenza A Virus Segment 8 in Setting Mammalian Host Range and Pathogenicity

PubMed Central

Turnbull, Matthew L.; Wise, Helen M.; Nicol, Marlynne Q.; Smith, Nikki; Dunfee, Rebecca L.; Beard, Philippa M.; Jagger, Brett W.; Ligertwood, Yvonne; Hardisty, Gareth R.; Xiao, Haixia; Benton, Donald J.; Coburn, Alice M.; Paulo, Joao A.; Gygi, Steven P.; McCauley, John W.; Taubenberger, Jeffery K.; Lycett, Samantha J.; Weekes, Michael P.; Dutia, Bernadette M.

2016-01-01

ABSTRACT Two alleles of segment 8 (NS) circulate in nonchiropteran influenza A viruses. The A allele is found in avian and mammalian viruses, but the B allele is viewed as being almost exclusively found in avian viruses. This might reflect the fact that one or both of its encoded proteins (NS1 and NEP) are maladapted for replication in mammalian hosts. To test this, a number of clade A and B avian virus-derived NS segments were introduced into human H1N1 and H3N2 viruses. In no case was the peak virus titer substantially reduced following infection of various mammalian cell types. Exemplar reassortant viruses also replicated to similar titers in mice, although mice infected with viruses with the avian virus-derived segment 8s had reduced weight loss compared to that achieved in mice infected with the A/Puerto Rico/8/1934 (H1N1) parent. In vitro, the viruses coped similarly with type I interferons. Temporal proteomics analysis of cellular responses to infection showed that the avian virus-derived NS segments provoked lower levels of expression of interferon-stimulated genes in cells than wild type-derived NS segments. Thus, neither the A nor the B allele of avian virus-derived NS segments necessarily attenuates virus replication in a mammalian host, although the alleles can attenuate disease. Phylogenetic analyses identified 32 independent incursions of an avian virus-derived A allele into mammals, whereas 6 introductions of a B allele were identified. However, A-allele isolates from birds outnumbered B-allele isolates, and the relative rates of Aves-to-Mammalia transmission were not significantly different. We conclude that while the introduction of an avian virus segment 8 into mammals is a relatively rare event, the dogma of the B allele being especially restricted is misleading, with implications in the assessment of the pandemic potential of avian influenza viruses. IMPORTANCE Influenza A virus (IAV) can adapt to poultry and mammalian species, inflicting a

Role of the B Allele of Influenza A Virus Segment 8 in Setting Mammalian Host Range and Pathogenicity.

PubMed

Turnbull, Matthew L; Wise, Helen M; Nicol, Marlynne Q; Smith, Nikki; Dunfee, Rebecca L; Beard, Philippa M; Jagger, Brett W; Ligertwood, Yvonne; Hardisty, Gareth R; Xiao, Haixia; Benton, Donald J; Coburn, Alice M; Paulo, Joao A; Gygi, Steven P; McCauley, John W; Taubenberger, Jeffery K; Lycett, Samantha J; Weekes, Michael P; Dutia, Bernadette M; Digard, Paul

2016-10-15

Two alleles of segment 8 (NS) circulate in nonchiropteran influenza A viruses. The A allele is found in avian and mammalian viruses, but the B allele is viewed as being almost exclusively found in avian viruses. This might reflect the fact that one or both of its encoded proteins (NS1 and NEP) are maladapted for replication in mammalian hosts. To test this, a number of clade A and B avian virus-derived NS segments were introduced into human H1N1 and H3N2 viruses. In no case was the peak virus titer substantially reduced following infection of various mammalian cell types. Exemplar reassortant viruses also replicated to similar titers in mice, although mice infected with viruses with the avian virus-derived segment 8s had reduced weight loss compared to that achieved in mice infected with the A/Puerto Rico/8/1934 (H1N1) parent. In vitro, the viruses coped similarly with type I interferons. Temporal proteomics analysis of cellular responses to infection showed that the avian virus-derived NS segments provoked lower levels of expression of interferon-stimulated genes in cells than wild type-derived NS segments. Thus, neither the A nor the B allele of avian virus-derived NS segments necessarily attenuates virus replication in a mammalian host, although the alleles can attenuate disease. Phylogenetic analyses identified 32 independent incursions of an avian virus-derived A allele into mammals, whereas 6 introductions of a B allele were identified. However, A-allele isolates from birds outnumbered B-allele isolates, and the relative rates of Aves-to-Mammalia transmission were not significantly different. We conclude that while the introduction of an avian virus segment 8 into mammals is a relatively rare event, the dogma of the B allele being especially restricted is misleading, with implications in the assessment of the pandemic potential of avian influenza viruses. Influenza A virus (IAV) can adapt to poultry and mammalian species, inflicting a great socioeconomic

SSR allelic variation in almond (Prunus dulcis Mill.).

PubMed

Xie, Hua; Sui, Yi; Chang, Feng-Qi; Xu, Yong; Ma, Rong-Cai

2006-01-01

Sixteen SSR markers including eight EST-SSR and eight genomic SSRs were used for genetic diversity analysis of 23 Chinese and 15 international almond cultivars. EST- and genomic SSR markers previously reported in species of Prunus, mainly peach, proved to be useful for almond genetic analysis. DNA sequences of 117 alleles of six of the 16 SSR loci were analysed to reveal sequence variation among the 38 almond accessions. For the four SSR loci with AG/CT repeats, no insertions or deletions were observed in the flanking regions of the 98 alleles sequenced. Allelic size variation of these loci resulted exclusively from differences in the structures of repeat motifs, which involved interruptions or occurrences of new motif repeats in addition to varying number of AG/CT repeats. Some alleles had a high number of uninterrupted repeat motifs, indicating that SSR mutational patterns differ among alleles at a given SSR locus within the almond species. Allelic homoplasy was observed in the SSR loci because of base substitutions, interruptions or compound repeat motifs. Substitutions in the repeat regions were found at two SSR loci, suggesting that point mutations operate on SSRs and hinder the further SSR expansion by introducing repeat interruptions to stabilize SSR loci. Furthermore, it was shown that some potential point mutations in the flanking regions are linked with new SSR repeat motif variation in almond and peach.

Allelic Variation of Risk for Anxiety Symptoms Moderates the Relation Between Adolescent Safety Behaviors and Social Anxiety Symptoms

PubMed Central

Thomas, Sarah A.; Weeks, Justin W.; Dougherty, Lea R.; Lipton, Melanie F.; Daruwala, Samantha E.; Kline, Kathryn

2015-01-01

Social anxiety often develops in adolescence, and precedes the onset of depression and substance use disorders. The link between social anxiety and use of behaviors to minimize distress in social situations (i.e., safety behaviors) is strong and for some patients, this link poses difficulty for engaging in, and benefiting from, exposure-based treatment. Yet, little is known about whether individual differences may moderate links between social anxiety and safety behaviors, namely variations in genetic alleles germane to anxiety. We examined the relation between adolescent social anxiety and expressions of safety behaviors, and whether allelic variation for anxiety moderates this relation. Adolescents (n=75; ages 14–17) were recruited from two larger studies investigating measurement of family relationships or adolescent social anxiety. Adolescents completed self-report measures about social anxiety symptoms and use of safety behaviors. They also provided saliva samples to assess allelic variations for anxiety from two genetic polymorphisms (BDNF rs6265; TAQ1A rs1800497). Controlling for adolescent age and gender, we observed a significant interaction between social anxiety symptoms and allelic variation (β=0.37, t=2.41, p=.02). Specifically, adolescents carrying allelic variations for anxiety evidenced a statistically significant and relatively strong positive relation between social anxiety symptoms and safety behaviors (β=0.73), whereas adolescents not carrying allelic variation evidenced a statistically non-significant and relatively weak relation (β=0.22). These findings have important implications for treating adolescent social anxiety, in that we identified an individual difference variable that can be used to identify people who evidence a particularly strong link between use of safety behaviors and expressing social anxiety. PMID:26692635

Mutant maize variety containing the glt1-1 allele

DOEpatents

Nelson, O.E.; Pan, D.

1994-07-19

A maize plant has in its genome a non-mutable form of a mutant allele designated vitX-8132. The allele is located at a locus designated as glt which conditions kernels having an altered starch characteristic. Maize plants including such a mutant allele produce a starch that does not increase in viscosity on cooling, after heating. 2 figs.

Mutant maize variety containing the glt1-1 allele

DOEpatents

Nelson, Oliver E.; Pan, David

1994-01-01

A maize plant has in its genome a non-mutable form of a mutant allele designated vitX-8132. The allele is located at a locus designated as glt which conditions kernels having an altered starch characteristic. Maize plants including such a mutant allele produce a starch that does not increase in viscosity on cooling, after heating.

Quantitative trait locus analysis of plasma cholesterol levels and body weight by controlling the effects of the Apoa2 allele in mice.

PubMed

Suto, Jun-ichi

2007-04-01

Colleagues and I previously performed quantitative trait locus (QTL) analysis on plasma total-cholesterol (T-CHO) levels in C57BL/6J (B6) x RR F2 mice. We identified only one significant QTL (Cq6) on chromosome 1 in a region containing the Apoa2 gene locus, a convincing candidate gene for Cq6. Because Cq6 was a highly significant QTL, we considered that the detection of other potential QTLs might be hindered. In the present study, QTL analysis was performed in B6.KK-Apoa2b N(8) x RR F2 mice [B6.KK-Apoa2b N(8) is a partial congenic strain carrying the Apoa2b allele from the KK strain, and RR also has the Apoa2b allele] by controlling of the effects of the Apoa2 allele, for identifying additional QTLs. Although no significant QTLs were identified, 2 suggestive QTLs were found on chromosomes 2 and 3 in place of the effects of the Apoa2 allele. A significant body weight QTL was identified on chromosome 3 (Bwq7, peak LOD score 5.2); its effect on body weight was not significant in previously analyzed B6 x RR F2 mice. Suggestive body weight QTL that had been identified in B6 x RR F2 mice on chromosome 4 (LOD score 3.8) was not identified in B6.KK-Apoa2b N(8) x RR F2 mice. Thus, contrary to expectation, the genetic control of body weight was also altered significantly by controlling of the effects of the Apoa2 allele. The QTL mapping strategy by controlling of the effects of a major QTL facilitated the identification of additional QTLs.

Reduced Height (Rht) Alleles Affect Wheat Grain Quality.

PubMed

Casebow, Richard; Hadley, Caroline; Uppal, Rajneet; Addisu, Molla; Loddo, Stefano; Kowalski, Ania; Griffiths, Simon; Gooding, Mike

2016-01-01

The effects of dwarfing alleles (reduced height, Rht) in near isogenic lines on wheat grain quality are characterised in field experiments and related to effects on crop height, grain yield and GA-sensitivity. Alleles included those that conferred GA-insensitivity (Rht-B1b, Rht-B1c, Rht-D1b, Rht-D1c) as well as those that retained GA-sensitivity (rht(tall), Rht8, Rht8 + Ppd-D1a, Rht12). Full characterisation was facilitated by including factors with which the effects of Rht alleles are known to interact for grain yield (i.e. system, [conventional or organic]; tillage intensity [plough-based, minimum or zero]; nitrogen fertilizer level [0-450 kg N/ha]; and genetic backgrounds varying in height [cvs Maris Huntsman, Maris Widgeon, and Mercia]. Allele effects on mean grain weight and grain specific weight were positively associated with final crop height: dwarfing reduced these quality criteria irrespective of crop management or GA-sensitivity. In all but two experiments the effects of dwarfing alleles on grain nitrogen and sulphur concentrations were closely and negatively related to effects on grain yield, e.g. a quadratic relationship between grain yield and crop height manipulated by the GA-insensitive alleles was mirrored by quadratic relationships for nitrogen and sulphur concentrations: the highest yields and most dilute concentrations occurred around 80cm. In one of the two exceptional experiments the GA-insensitive Rht-B1b and Rht-B1c significantly (P<0.05) reduced grain nitrogen concentration in the absence of an effect on yield, and in the remaining experiment the GA-sensitive Rht8 significantly reduced both grain yield and grain nitrogen concentration simultaneously. When Rht alleles diluted grain nitrogen concentration, N:S ratios and SDS-sedimentation volumes were often improved. Hagberg falling number (HFN) was negatively related to crop height but benefits from dwarfing were only seen for GA-insensitive alleles. For HFN, therefore, there was the

Association of the apolipoprotein E {epsilon}4 allele with clinical subtypes of autopsy-confirmed Alzheimer`s Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zubenko, G.S.; Stiffler, S.; Kopp, U.

1994-09-15

Consistent with previous reports, we observed a significant association of the APOE {epsilon}4 allele with Alzheimer`s Disease (AD) in a series of 91 autopsy-confirmed cases. The {epsilon}4 allele frequency was higher in cases with a family history of AD-like dementia (0.54 {+-} 0.07), although the {epsilon}4 allele frequency in the AD cases with a negative family history (0.38 {+-} 0.05) remained significantly greater than that for the non-AD control group (0.13 {+-} 0.03). A similar increase in {epsilon}4 allele frequency (0.54 {+-} 0.07) was observed in the AD cases with amyloid angiopathy, compared to those who did not have amyloidmore » angiopathy (0.35 {+-} 0.04). Contrary to previous reports, no effect of the dosage of the {epsilon}4 allele was found on the age of onset of dementia among the AD cases and, contrary to reports suggesting an association of {epsilon}4 and atherosclerosis, the {epsilon}4 allele frequency was similar in cases with or without concurrent brain infarcts. Modest but consistent correlations were observed between the dosage of {epsilon}4 alleles and the cortical density of senile plaques, but not neurofibrillary tangles. The last finding suggests that the pathogenic events mediated by the {epsilon}4 allele may be more directly involved in the formation of senile plaques, the identifying lesions in AD, than neurofibrillary tangles. A robust association of both the presence of an {epsilon}4 allele and a family history of AD-like dementia with concurrent amyloid angiopathy occurred within our sample of AD cases. This association arose from an interaction of the {epsilon}4 allele with a separate familial factor for which a family history of dementia served as a surrogate. These results suggest that amyloid angiopathy may be a common or central feature of a form of familial AD that is associated with the transmission of the APOE {epsilon}4 allele. 22 refs., 2 figs., 5 tabs.« less

Detection of Ancestry Informative HLA Alleles Confirms the Admixed Origins of Japanese Population

PubMed Central

Nakaoka, Hirofumi; Mitsunaga, Shigeki; Hosomichi, Kazuyoshi; Shyh-Yuh, Liou; Sawamoto, Taiji; Fujiwara, Tsutomu; Tsutsui, Naohisa; Suematsu, Koji; Shinagawa, Akira; Inoko, Hidetoshi; Inoue, Ituro

2013-01-01

The polymorphisms in the human leukocyte antigen (HLA) region are powerful tool for studying human evolutionary processes. We investigated genetic structure of Japanese by using five-locus HLA genotypes (HLA-A, -B, -C, -DRB1, and -DPB1) of 2,005 individuals from 10 regions of Japan. We found a significant level of population substructure in Japanese; particularly the differentiation between Okinawa Island and mainland Japanese. By using a plot of the principal component scores, we identified ancestry informative alleles associated with the underlying population substructure. We examined extent of linkage disequilibrium (LD) between pairs of HLA alleles on the haplotypes that were differentiated among regions. The LDs were strong and weak for pairs of HLA alleles characterized by low and high frequencies in Okinawa Island, respectively. The five-locus haplotypes whose alleles exhibit strong LD were unique to Japanese and South Korean, suggesting that these haplotypes had been recently derived from the Korean Peninsula. The alleles characterized by high frequency in Japanese compared to South Korean formed segmented three-locus haplotype that was commonly found in Aleuts, Eskimos, and North- and Meso-Americans but not observed in Korean and Chinese. The serologically equivalent haplotype was found in Orchid Island in Taiwan, Mongol, Siberia, and Arctic regions. It suggests that early Japanese who existed prior to the migration wave from the Korean Peninsula shared ancestry with northern Asian who moved to the New World via the Bering Strait land bridge. These results may support the admixture model for peopling of Japanese Archipelago. PMID:23577161

Detection of ancestry informative HLA alleles confirms the admixed origins of Japanese population.

PubMed

Nakaoka, Hirofumi; Mitsunaga, Shigeki; Hosomichi, Kazuyoshi; Shyh-Yuh, Liou; Sawamoto, Taiji; Fujiwara, Tsutomu; Tsutsui, Naohisa; Suematsu, Koji; Shinagawa, Akira; Inoko, Hidetoshi; Inoue, Ituro

2013-01-01

The polymorphisms in the human leukocyte antigen (HLA) region are powerful tool for studying human evolutionary processes. We investigated genetic structure of Japanese by using five-locus HLA genotypes (HLA-A, -B, -C, -DRB1, and -DPB1) of 2,005 individuals from 10 regions of Japan. We found a significant level of population substructure in Japanese; particularly the differentiation between Okinawa Island and mainland Japanese. By using a plot of the principal component scores, we identified ancestry informative alleles associated with the underlying population substructure. We examined extent of linkage disequilibrium (LD) between pairs of HLA alleles on the haplotypes that were differentiated among regions. The LDs were strong and weak for pairs of HLA alleles characterized by low and high frequencies in Okinawa Island, respectively. The five-locus haplotypes whose alleles exhibit strong LD were unique to Japanese and South Korean, suggesting that these haplotypes had been recently derived from the Korean Peninsula. The alleles characterized by high frequency in Japanese compared to South Korean formed segmented three-locus haplotype that was commonly found in Aleuts, Eskimos, and North- and Meso-Americans but not observed in Korean and Chinese. The serologically equivalent haplotype was found in Orchid Island in Taiwan, Mongol, Siberia, and Arctic regions. It suggests that early Japanese who existed prior to the migration wave from the Korean Peninsula shared ancestry with northern Asian who moved to the New World via the Bering Strait land bridge. These results may support the admixture model for peopling of Japanese Archipelago.

Management of co-existing diabetes mellitus and dyslipidemia: defining the role of thiazolidinediones.

PubMed

Florkowski, Chris M

2002-01-01

The observed reduction in macrovascular outcomes in the United Kingdom Progressive Diabetes Study (UKPDS) trial in patients with type 2 diabetes mellitus (DM), treated intensively with insulin or sulfonylureas, was of borderline significance (p = 0.052). This may be because of the role of factors other than glycemic control in the etiology of macrovascular disease. The UKPDS and other studies have suggested that lipid parameters are potent predictors of adverse outcomes in patients with type 2 DM. In patients with DM, dyslipidemia is characterized by elevated serum triglycerides and low high density lipoprotein-cholesterol (HDL-C) with normal total serum cholesterol levels and usually accompanied by an elevation of atherogenic, small, dense low density lipoprotein-cholesterol (LDL-C) particles. Dyslipidemia is only partly corrected by dietary and lifestyle modifications and pharmacological glycemic control in patients with DM. Several guidelines, including those published by the New Zealand Heart Foundation, suggest that lipid-modifying therapies are appropriate in patients considered to be at high or very high risk of a cardiac event. This includes patients with established vascular disease. Some recent studies suggest that patients with type 2 DM have risk comparable to patients without DM, but have experienced previous myocardial infarction (MI). Subgroup analysis of trials including the Scandinavian Simvastatin Survival Study (4S) and Cholesterol and Recurrent Events (CARE), which included patients with DM, have shown a significant reduction in adverse outcomes, although many patients with DM and dyslipidemia were excluded. Of lipid-lowering drugs, fibric acid derivatives are probably the most appropriate for patients with DM and dyslipidemia and their role is being evaluated in large, long-term outcome studies such as Fenofibrate Intervention and Event Lowering in Diabetes (FIELD). Thiazolidinediones, a new class of compound for treating patients with type 2

GACT: a Genome build and Allele definition Conversion Tool for SNP imputation and meta-analysis in genetic association studies.

PubMed

Sulovari, Arvis; Li, Dawei

2014-07-19

Genome-wide association studies (GWAS) have successfully identified genes associated with complex human diseases. Although much of the heritability remains unexplained, combining single nucleotide polymorphism (SNP) genotypes from multiple studies for meta-analysis will increase the statistical power to identify new disease-associated variants. Meta-analysis requires same allele definition (nomenclature) and genome build among individual studies. Similarly, imputation, commonly-used prior to meta-analysis, requires the same consistency. However, the genotypes from various GWAS are generated using different genotyping platforms, arrays or SNP-calling approaches, resulting in use of different genome builds and allele definitions. Incorrect assumptions of identical allele definition among combined GWAS lead to a large portion of discarded genotypes or incorrect association findings. There is no published tool that predicts and converts among all major allele definitions. In this study, we have developed a tool, GACT, which stands for Genome build and Allele definition Conversion Tool, that predicts and inter-converts between any of the common SNP allele definitions and between the major genome builds. In addition, we assessed several factors that may affect imputation quality, and our results indicated that inclusion of singletons in the reference had detrimental effects while ambiguous SNPs had no measurable effect. Unexpectedly, exclusion of genotypes with missing rate > 0.001 (40% of study SNPs) showed no significant decrease of imputation quality (even significantly higher when compared to the imputation with singletons in the reference), especially for rare SNPs. GACT is a new, powerful, and user-friendly tool with both command-line and interactive online versions that can accurately predict, and convert between any of the common allele definitions and between genome builds for genome-wide meta-analysis and imputation of genotypes from SNP-arrays or deep

Erasure and reestablishment of random allelic expression imbalance after epigenetic reprogramming.

PubMed

Jeffries, Aaron Richard; Uwanogho, Dafe Aghogho; Cocks, Graham; Perfect, Leo William; Dempster, Emma; Mill, Jonathan; Price, Jack

2016-10-01

Clonal level random allelic expression imbalance and random monoallelic expression provides cellular heterogeneity within tissues by modulating allelic dosage. Although such expression patterns have been observed in multiple cell types, little is known about when in development these stochastic allelic choices are made. We examine allelic expression patterns in human neural progenitor cells before and after epigenetic reprogramming to induced pluripotency, observing that loci previously characterized by random allelic expression imbalance (0.63% of expressed genes) are generally reset to a biallelic state in induced pluripotent stem cells (iPSCs). We subsequently neuralized the iPSCs and profiled isolated clonal neural stem cells, observing that significant random allelic expression imbalance is reestablished at 0.65% of expressed genes, including novel loci not found to show allelic expression imbalance in the original parental neural progenitor cells. Allelic expression imbalance was associated with altered DNA methylation across promoter regulatory regions, with clones characterized by skewed allelic expression being hypermethylated compared to their biallelic sister clones. Our results suggest that random allelic expression imbalance is established during lineage commitment and is associated with increased DNA methylation at the gene promoter. © 2016 Jeffries et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

JAK2V617F mutation is associated with special alleles in essential thrombocythemia.

PubMed

Hsiao, Hui-Hua; Liu, Yi-Chang; Tsai, Hui-Jen; Lee, Ching-Ping; Hsu, Jui-Feng; Lin, Sheng-Fung

2011-03-01

Janus kinase 2 mutation (JAK2V617F) has been identified in myeloproliferative neoplasms. Furthermore, special single nucleoside polymorphisms (SNPs) have been found to be associated with the JAK2V617F mutation. Therefore, the associations among JAK2V617F and special SNPs and the allelic location between them were investigated in patients with essential thrombocythemia (ET). A total of 61 patients with ET and 106 healthy individuals were enrolled. The PCR-RFLP method was applied to investigate the pattern of three SNPs, rs10974944, rs12343867, and rs12340895. Allele-specific PCR was used to examine the allelic location between rs10974944 and JAK2V617F. Among the patients with ET, 34 (55.7%, 34/61) were JAK2V617F positive (heterozygous) while the other 27 (44.3%, 27/61) were negative, and there were no MPLW515L/K mutations noted. The pattern of special SNPs in JAK2V617F(+) was significantly different from that in normal individuals (p <0.05), while there was no difference between JAK2V617F(-) patients and normal individuals. Allele-specific PCR showed high association of a cis-location between the special G-allele of rs10974944 and JAK2V617F(+). Based on this small numbered study, the results show the association between special SNPs and JAK2V617F mutation and a cis-location between the special G-allelic form of rs10974944 and the JAK2V617F mutation. These data highlight a close relationship between them in patients with ET.

Genetic association of APOB polymorphisms with variation in serum lipid profile among the Kuwait population.

PubMed

Al-Bustan, Suzanne A; Alnaqeeb, Majed A; Annice, Babitha G; Ebrahim, Ghada A; Refai, Thanaa M

2014-10-08

Several studies have identified APOB as a candidate gene predisposing individuals to dyslipidemia. Polymorphisms including the signal peptide (rs11279109), codon 2488 XbaI (rs1042031), codon 3611 MspI (rs693), codon 4154 EcoRI (rs1801701) and the 3' variable number of tandem repeats have been reported to be associated with dyslipidemia in several populations. With limited studies on Arabs, this study aimed to investigate the genetic association of APOB polymorphisms and assess the potential influence of minor and rare alleles on serum lipid levels in the Kuwaiti population. A total of 795 Kuwaiti subjects, documented with phenotypic data and fasting serum lipid levels, were genotyped for the five polymorphisms using PCR, PCR-RFLP and gene fragment analysis. Genotype and allele association with variation in serum lipid levels as well as haplotypes were analyzed using chi-square test, univariate and logistic regression analysis. Analysis of the genotype and allele frequencies distribution revealed a significant positive association between the APOB signal peptide and 3611 MspI polymorphisms with increased levels of triglycerides (statistical power of 80%). Haplotype analysis further supported the findings by showing that carriers of haplotypes (IX-M-E+M) had significantly lower mean (SD) TG levels (0.86 ± 0.07) as compared to non-carriers (1.01 ± 0.02). Significance was also observed with regards to positive family history of hypercholesterolemia. The results imply a "protective role" for two alleles (rs11279109 and rs1801701) in which logistic regression analysis showed a significant half-fold decrease in the risk for heterozygotes of rs11279109 and an 8.8 fold decrease in the risk for homozygous M-M- of rs1801701 of having lower TG levels (<1.70 mmol/L) in individuals. This suggests that genetic interaction between various polymorphisms at different gene loci act in linkage disequilibrium to affect serum TG levels. Apo B genotyping may be a useful adjunct

The allele combinations of three loci based on, liver, stomach cancers, hematencephalon, COPD and normal population: A preliminary study.

PubMed

Gai, Liping; Liu, Hui; Cui, Jing-Hui; Yu, Weijian; Ding, Xiao-Dong

2017-03-20

The purpose of this study was to examine the specific allele combinations of three loci connected with the liver cancers, stomach cancers, hematencephalon and patients with chronic obstructive pulmonary disease (COPD) and to explore the feasibility of the research methods. We explored different mathematical methods for statistical analyses to assess the association between the genotype and phenotype. At the same time we still analyses the statistical results of allele combinations of three loci by difference value method and ratio method. All the DNA blood samples were collected from patients with 50 liver cancers, 75 stomach cancers, 50 hematencephalon, 72 COPD and 200 normal populations. All the samples were from Chinese. Alleles from short tandem repeat (STR) loci were determined using the STR Profiler plus PCR amplification kit (15 STR loci). Previous research was based on combinations of single-locus alleles, and combinations of cross-loci (two loci) alleles. Allele combinations of three loci were obtained by computer counting and stronger genetic signal was obtained. The methods of allele combinations of three loci can help to identify the statistically significant differences of allele combinations between liver cancers, stomach cancers, patients with hematencephalon, COPD and the normal population. The probability of illness followed different rules and had apparent specificity. This method can be extended to other diseases and provide reference for early clinical diagnosis. Copyright © 2016. Published by Elsevier B.V.

Functional PMS2 hybrid alleles containing a pseudogene-specific missense variant trace back to a single ancient intrachromosomal recombination event.

PubMed

Ganster, Christina; Wernstedt, Annekatrin; Kehrer-Sawatzki, Hildegard; Messiaen, Ludwine; Schmidt, Konrad; Rahner, Nils; Heinimann, Karl; Fonatsch, Christa; Zschocke, Johannes; Wimmer, Katharina

2010-05-01

Sequence exchange between PMS2 and its pseudogene PMS2CL, embedded in an inverted duplication on chromosome 7p22, has been reported to be an ongoing process that leads to functional PMS2 hybrid alleles containing PMS2- and PMS2CL-specific sequence variants at the 5'-and the 3'-end, respectively. The frequency of PMS2 hybrid alleles, their biological significance, and the mechanisms underlying their formation are largely unknown. Here we show that overall hybrid alleles account for one-third of 384 PMS2 alleles analyzed in individuals of different ethnic backgrounds. Depending on the population, 14-60% of hybrid alleles carry PMS2CL-specific sequences in exons 13-15, the remainder only in exon 15. We show that exons 13-15 hybrid alleles, named H1 hybrid alleles, constitute different haplotypes but trace back to a single ancient intrachromosomal recombination event with crossover. Taking advantage of an ancestral sequence variant specific for all H1 alleles we developed a simple gDNA-based polymerase chain reaction (PCR) assay that can be used to identify H1-allele carriers with high sensitivity and specificity (100 and 99%, respectively). Because H1 hybrid alleles harbor missense variant p.N775S of so far unknown functional significance, we assessed the H1-carrier frequency in 164 colorectal cancer patients. So far, we found no indication that the variant plays a major role with regard to cancer susceptibility. (c) 2010 Wiley-Liss, Inc.

Mining the LIPG Allelic Spectrum Reveals the Contribution of Rare and Common Regulatory Variants to HDL Cholesterol

PubMed Central

Raghavan, Avanthi; Neeli, Hemanth; Jin, Weijun; Badellino, Karen O.; Demissie, Serkalem; Manning, Alisa K.; DerOhannessian, Stephanie L.; Wolfe, Megan L.; Cupples, L. Adrienne; Li, Mingyao; Kathiresan, Sekar; Rader, Daniel J.

2011-01-01

Genome-wide association studies (GWAS) have successfully identified loci associated with quantitative traits, such as blood lipids. Deep resequencing studies are being utilized to catalogue the allelic spectrum at GWAS loci. The goal of these studies is to identify causative variants and missing heritability, including heritability due to low frequency and rare alleles with large phenotypic impact. Whereas rare variant efforts have primarily focused on nonsynonymous coding variants, we hypothesized that noncoding variants in these loci are also functionally important. Using the HDL-C gene LIPG as an example, we explored the effect of regulatory variants identified through resequencing of subjects at HDL-C extremes on gene expression, protein levels, and phenotype. Resequencing a portion of the LIPG promoter and 5′ UTR in human subjects with extreme HDL-C, we identified several rare variants in individuals from both extremes. Luciferase reporter assays were used to measure the effect of these rare variants on LIPG expression. Variants conferring opposing effects on gene expression were enriched in opposite extremes of the phenotypic distribution. Minor alleles of a common regulatory haplotype and noncoding GWAS SNPs were associated with reduced plasma levels of the LIPG gene product endothelial lipase (EL), consistent with its role in HDL-C catabolism. Additionally, we found that a common nonfunctional coding variant associated with HDL-C (rs2000813) is in linkage disequilibrium with a 5′ UTR variant (rs34474737) that decreases LIPG promoter activity. We attribute the gene regulatory role of rs34474737 to the observed association of the coding variant with plasma EL levels and HDL-C. Taken together, the findings show that both rare and common noncoding regulatory variants are important contributors to the allelic spectrum in complex trait loci. PMID:22174694

Analysis of an "off-ladder" allele at the Penta D short tandem repeat locus.

PubMed

Yang, Y L; Wang, J G; Wang, D X; Zhang, W Y; Liu, X J; Cao, J; Yang, S L

2015-11-25

Kinship testing of a father and his son from Guangxi, China, the location of the Zhuang minority people, was performed using the PowerPlex® 18D System with a short tandem repeat typing kit. The results indicated that both the father and his son had an off-ladder allele at the Penta D locus, with a genetic size larger than that of the maximal standard allelic ladder. To further identify this locus, monogenic amplification, gene cloning, and genetic sequencing were performed. Sequencing analysis demonstrated that the fragment size of the Penta D-OL locus was 469 bp and the core sequence was [AAAGA]21, also called Penta D-21. The rare Penta D-21 allele was found to be distributed among the Zhuang population from the Guangxi Zhuang Autonomous Region of China; therefore, this study improved the range of DNA data available for this locus and enhanced our ability for individual identification of gene loci.

Allelic database and accession divergence of a Brazilian mango collection based on microsatellite markers.

PubMed

Dos Santos Ribeiro, I C N; Lima Neto, F P; Santos, C A F

2012-12-19

Allelic patterns and genetic distances were examined in a collection of 103 foreign and Brazilian mango (Mangifera indica) accessions in order to develop a reference database to support cultivar protection and breeding programs. An UPGMA dendrogram was generated using Jaccard's coefficients from a distance matrix based on 50 alleles of 12 microsatellite loci. The base pair number was estimated by the method of inverse mobility. The cophenetic correlation was 0.8. The accessions had a coefficient of similarity from 30 to 100%, which reflects high genetic variability. Three groups were observed in the UPGMA dendrogram; the first group was formed predominantly by foreign accessions, the second group was formed by Brazilian accessions, and the Dashehari accession was isolated from the others. The 50 microsatellite alleles did not separate all 103 accessions, indicating that there are duplicates in this mango collection. These 12 microsatellites need to be validated in order to establish a reliable set to identify mango cultivars.

Prion protein genotype survey confirms low frequency of scrapie-resistant K222 allele in British goat herds.

PubMed

Goldmann, W; Marier, E; Stewart, P; Konold, T; Street, S; Langeveld, J; Windl, O; Ortiz-Pelaez, A

2016-02-13

Scrapie in goats is a transmissible, fatal prion disease, which is endemic in the British goat population. The recent success in defining caprine PRNP gene variants that provide resistance to experimental and natural classical scrapie has prompted the authors to conduct a survey of PRNP genotypes in 10 goat breeds and 52 herds to find goats with the resistant K222 allele. They report here the frequencies in 1236 tested animals of the resistance-associated K222 and several other alleles by breed and herd. Eight animals were found to be heterozygous QK222 goats (0.64 per cent genotype frequency, 95 per cent CI 0.28 to 1.27 per cent) but no homozygous KK222 goats were detected. The K222 allele was found in Saanen, Toggenburg and Anglo-Nubian goats. The fact that only a few goats with the K222 allele have been identified does not preclude the possibility to design and implement successful breeding programmes at national level. British Veterinary Association.

Complex and multi-allelic copy number variation in human disease

PubMed Central

McCarroll, Steven A.

2015-01-01

Hundreds of copy number variants are complex and multi-allelic, in that they have many structural alleles and have rearranged multiple times in the ancestors who contributed chromosomes to current humans. Not only are the relationships of these multi-allelic CNVs (mCNVs) to phenotypes generally unknown, but many mCNVs have not yet been described at the basic levels—alleles, allele frequencies, structural features—that support genetic investigation. To date, most reported disease associations to these variants have been ascertained through candidate gene studies. However, only a few associations have reached the level of acceptance defined by durable replications in many cohorts. This likely stems from longstanding challenges in making precise molecular measurements of the alleles individuals have at these loci. However, approaches for mCNV analysis are improving quickly, and some of the unique characteristics of mCNVs may assist future association studies. Their various structural alleles are likely to have different magnitudes of effect, creating a natural allelic series of growing phenotypic impact and giving investigators a set of natural predictions and testable hypotheses about the extent to which each allele of an mCNV predisposes to a phenotype. Also, mCNVs’ low-to-modest correlation to individual single-nucleotide polymorphisms (SNPs) may make it easier to distinguish between mCNVs and nearby SNPs as the drivers of an association signal, and perhaps, make it possible to preliminarily screen candidate loci, or the entire genome, for the many mCNV–disease relationships that remain to be discovered. PMID:26163405

Analysis for complete genomic sequence of HLA-B and HLA-C alleles in the Chinese Han population.

PubMed

Zhu, F; He, Y; Zhang, W; He, J; He, J; Xu, X; Lv, H; Yan, L

2011-08-01

In the present study, we have determined the complete genomic sequence and analysed the intron polymorphism of partial HLA-B and HLA-C alleles in the Chinese Han population. Over 3.0 kb DNA fragments of HLA-B and HLA-C loci were amplified by polymerase chain reaction from partial 5' untranslated region to 3' noncoding region respectively, and then the amplified products were sequenced. Full-length nucleotide sequences of 14 HLA-B alleles and 10 HLA-C alleles were obtained and have been submitted to GenBank and IMGT/HLA database. Two novel alleles of HLA-B*52:01:01:02 and HLA-B*59:01:01:02 were identified, and the complete genomic sequence of HLA-B*52:01:01:01 was firstly reported. Totally 157 and 167 polymorphism positions were found in the full-length genomic sequence of HLA-B and HLA-C loci respectively. Our results suggested that many single nucleotide polymorphisms existed in the exon and intron regions, and the data can provide useful information for understanding the evolution of HLA-B and HLA-C alleles. © 2011 Blackwell Publishing Ltd.

An evolutionary approach to major histocompatibility diversity based on allele supertypes.

PubMed

Naugler, Christopher; Liwski, Robert

2008-01-01

Human leukocyte antigens are traditionally classified by serologic or molecular techniques into a bewildering variety of alleles. It is generally believed that this allelic diversity is maintained by selection pressures for inbreeding avoidance and/or maximal immune system diversity. While the usual antigen-based classification of individual alleles may be most appropriate in the artificial situation of tissue transplantation, we hypothesize that a functional classification based on allele supertypes may represent a more biologically relevant way to view MHC diversity in the contexts of mate choice and disease pathogenesis. Furthermore, immune system diversity could be quantitatively estimated by calculating a Supertype Diversity Index (SDI) which is the number of different MHC supertypes possessed by an individual. This hypothesis generates a number of testable predictions. First, it predicts that a reduced inherited diversity of MHC allele supertypes may predispose to the development of malignancies because of a decreased native ability to present different tumor-associated antigens. Furthermore, specific autoimmune diseases may be associated with the presence or absence of a particular MHC supertype rather than a particular MHC haplotype. In transplant medicine, it is possible that unmatched alleles may trigger a weaker foreign antigen response if they are matched by allele supertype. Finally, there have been several studies documenting dissortative mating in humans for dissimilar MHC alleles. We predict that natural selection should favor maximization of the heterozygosity of allele supertypes instead of the heterozygosity of individual alleles and that the previously observed dissortative mating may actually be an adaptive strategy to maximize allele supertype diversity.

Structure of allelic variants of subtype 5 of histone H1 in pea Pisum sativum L.

PubMed

Bogdanova, V S; Lester, D R; Berdnikov, V A; Andersson, I

2005-06-01

The pea genome contains seven histone H1 genes encoding different subtypes. Previously, the DNA sequence of only one gene, His1, coding for the subtype H1-1, had been identified. We isolated a histone H1 allele from a pea genomic DNA library. Data from the electrophoretic mobility of the pea H1 subtypes and their N-bromosuccinimide cleavage products indicated that the newly isolated gene corresponded to the H1-5 subtype encoded by His5. We confirmed this result by sequencing the gene from three pea lines with H1-5 allelic variants of altered electrophoretic mobility. The allele of the slow H1-5 variant differed from the standard allele by a nucleotide substitution that caused the replacement of the positively charged lysine with asparagine in the DNA-interacting domain of the histone molecule. A temperature-related occurrence had previously been demonstrated for this H1-5 variant in a study on a worldwide collection of pea germplasm. The variant tended to occur at higher frequencies in geographic regions with a cold climate. The fast allelic variant of H1-5 displayed a deletion resulting in the loss of a duplicated pentapeptide in the C-terminal domain.

Genome-wide analysis of allele frequency change in sunflower crop-wild hybrid populations evolving under natural conditions.

PubMed

Corbi, Jonathan; Baack, Eric J; Dechaine, Jennifer M; Seiler, Gerald; Burke, John M

2018-01-01

Crop-wild hybridization occurs in numerous plant species and could alter the genetic structure and evolutionary dynamics of wild populations. Studying crop-derived alleles in wild populations is also relevant to assessing/mitigating the risks associated with transgene escape. To date, crop-wild hybridization has generally been examined via short-term studies, typically within a single generation, focusing on few traits or genetic markers. Little is known about patterns of selection on crop-derived alleles over multiple generations, particularly at a genome-wide scale. Here, we documented patterns of natural selection in an experimental crop × wild sunflower population that was allowed to evolve under natural conditions for two generations at two locations. Allele frequencies at a genome-wide collection of SNPs were tracked across generations, and a common garden experiment was conducted to compare trait means between generations. These data allowed us to identify instances of selection on crop-derived alleles/traits and, in concert with QTL mapping results, test for congruence between our genotypic and phenotypic results. We found that natural selection overwhelmingly favours wild alleles and phenotypes. However, crop alleles in certain genomic regions can be favoured, and these changes often occurred in parallel across locations. We did not, however, consistently observe close agreement between our genotypic and phenotypic results. For example, when a trait evolved towards the wild phenotype, wild QTL alleles associated with that trait did not consistently increase in frequency. We discuss these results in the context of crop allele introgression into wild populations and implications for the management of GM crops. © 2017 John Wiley & Sons Ltd.

Divergent Hd1, Ghd7, and DTH7 Alleles Control Heading Date and Yield Potential of Japonica Rice in Northeast China.

PubMed

Ye, Jing; Niu, Xiaojun; Yang, Yaolong; Wang, Shan; Xu, Qun; Yuan, Xiaoping; Yu, Hanyong; Wang, Yiping; Wang, Shu; Feng, Yue; Wei, Xinghua

2018-01-01

The heading date is a vital factor in achieving a full rice yield. Cultivars with particular flowering behaviors have been artificially selected to survive in the long-day and low-temperature conditions of Northeast China. To dissect the genetic mechanism responsible for heading date in rice populations from Northeast China, association mapping was performed to identify major controlling loci. A genome-wide association study (GWAS) identified three genetic loci, Hd1 , Ghd7 , and DTH7 , using general and mixed linear models. The three genes were sequenced to analyze natural variations and identify their functions. Loss-of-function alleles of these genes contributed to early rice heading dates in the northern regions of Northeast China, while functional alleles promoted late rice heading dates in the southern regions of Northeast China. Selecting environmentally appropriate allele combinations in new varieties is recommended during breeding. Introducing the early indica rice's genetic background into Northeast japonica rice is a reasonable strategy for improving genetic diversity.

EOMES-positive CD4+ T cells are increased in PTPN22 (1858T) risk allele carriers.

PubMed

Chemin, Karine; Ramsköld, Daniel; Diaz-Gallo, Lina-Marcela; Herrath, Jessica; Houtman, Miranda; Tandre, Karolina; Rönnblom, Lars; Catrina, Anca; Malmström, Vivianne

2018-04-01

The presence of the PTPN22 risk allele (1858T) is associated with several autoimmune diseases including rheumatoid arthritis (RA). Despite a number of studies exploring the function of PTPN22 in T cells, the exact impact of the PTPN22 risk allele on T-cell function in humans is still unclear. In this study, using RNA sequencing, we show that, upon TCR-activation, naïve human CD4 + T cells homozygous for the PTPN22 risk allele overexpress a set of genes including CFLAR and 4-1BB, which are important for cytotoxic T-cell differentiation. Moreover, the protein expression of the T-box transcription factor Eomesodermin (EOMES) was increased in T cells from healthy donors homozygous for the PTPN22 risk allele and correlated with a decreased number of naïve CD4 + T cells. There was no difference in the frequency of other CD4 + T-cell subsets (Th1, Th17, Tfh, Treg). Finally, an accumulation of EOMES + CD4 + T cells was observed in synovial fluid of RA patients with a more pronounced production of Perforin-1 in PTPN22 risk allele carriers. Altogether, we propose a novel mechanism of action of PTPN22 risk allele through the generation of cytotoxic CD4 + T cells and identify EOMES + CD4 + T cells as a relevant T-cell subset in RA pathogenesis. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Early changes of blood lipid levels during psychotropic drug treatment as predictors of long-term lipid changes and of new onset dyslipidemia.

PubMed

Delacrétaz, Aurélie; Vandenberghe, Frederik; Gholam-Rezaee, Mehdi; Saigi Morgui, Nuria; Glatard, Anaïs; Thonney, Jacques; Solida-Tozzi, Alessandra; Kolly, Stéphane; Gallo, Sylfa Fassassi; Baumann, Philipp; Berney, Sylvie; Zulauff, Sandrine Valloton; Aubry, Jean-Michel; Hasler, Roland; Ebbing, Karsten; von Gunten, Armin; Conus, Philippe; Eap, Chin B

Cardiovascular diseases and dyslipidemia represent a major health issue in psychiatry. Many psychotropic drugs can induce a rapid and substantial increase of blood lipid levels. This study aimed to determine the potential predictive power of an early change of blood lipid levels during psychotropic treatment on long-term change and on dyslipidemia development. Data were obtained from a prospective study including 181 psychiatric patients with metabolic parameters monitored during the first year of treatment and with adherence ascertained. Blood lipid levels (ie, total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], non-high-density lipoprotein cholesterol [non-HDL-C], and fasting triglycerides [TGs]) were measured at baseline and after 1, 3, and/or 12 months of treatment. Receiver-operating characteristic analyses indicated that early (ie, after 1 month of psychotropic treatment) increases (≥5%) for TC, LDL-C, TG, and non-HDL-C and decrease (≥5%) for HDL-C were the best predictors for clinically relevant modifications of blood lipid levels after 3 months of treatment (≥30% TC, ≥40% LDL-C, ≥45% TG, ≥55% non-HDL-C increase, and ≥20% HDL-C decrease; sensitivity 70%-100%, specificity 53%-72%). Predictive powers of these models were confirmed by fitting longitudinal multivariate models in the same cohort (P ≤ .03) as well as in a replication cohort (n = 79; P ≤ .003). Survival models showed significantly higher incidences of new onset dyslipidemia (TC, LDL-C, and non-HDL-C hypercholesterolemia, HDL-C hypocholesterolemia, and hypertriglyceridemia) for patients with early changes of blood lipid levels compared to others (P ≤ .01). Early modifications of blood lipid levels following prescription of psychotropic drugs inducing dyslipidemia should therefore raise questions on clinical strategies to control long-term dyslipidemia. Copyright © 2017 National Lipid Association. Published

Reduced Height (Rht) Alleles Affect Wheat Grain Quality

PubMed Central

Casebow, Richard; Hadley, Caroline; Uppal, Rajneet; Addisu, Molla; Loddo, Stefano; Kowalski, Ania; Griffiths, Simon; Gooding, Mike

2016-01-01

The effects of dwarfing alleles (reduced height, Rht) in near isogenic lines on wheat grain quality are characterised in field experiments and related to effects on crop height, grain yield and GA-sensitivity. Alleles included those that conferred GA-insensitivity (Rht-B1b, Rht-B1c, Rht-D1b, Rht-D1c) as well as those that retained GA-sensitivity (rht(tall), Rht8, Rht8 + Ppd-D1a, Rht12). Full characterisation was facilitated by including factors with which the effects of Rht alleles are known to interact for grain yield (i.e. system, [conventional or organic]; tillage intensity [plough-based, minimum or zero]; nitrogen fertilizer level [0–450 kg N/ha]; and genetic backgrounds varying in height [cvs Maris Huntsman, Maris Widgeon, and Mercia]. Allele effects on mean grain weight and grain specific weight were positively associated with final crop height: dwarfing reduced these quality criteria irrespective of crop management or GA-sensitivity. In all but two experiments the effects of dwarfing alleles on grain nitrogen and sulphur concentrations were closely and negatively related to effects on grain yield, e.g. a quadratic relationship between grain yield and crop height manipulated by the GA-insensitive alleles was mirrored by quadratic relationships for nitrogen and sulphur concentrations: the highest yields and most dilute concentrations occurred around 80cm. In one of the two exceptional experiments the GA-insensitive Rht-B1b and Rht-B1c significantly (P<0.05) reduced grain nitrogen concentration in the absence of an effect on yield, and in the remaining experiment the GA-sensitive Rht8 significantly reduced both grain yield and grain nitrogen concentration simultaneously. When Rht alleles diluted grain nitrogen concentration, N:S ratios and SDS-sedimentation volumes were often improved. Hagberg falling number (HFN) was negatively related to crop height but benefits from dwarfing were only seen for GA-insensitive alleles. For HFN, therefore, there was the

Exploring new alleles for frost tolerance in winter rye.

PubMed

Erath, Wiltrud; Bauer, Eva; Fowler, D Brian; Gordillo, Andres; Korzun, Viktor; Ponomareva, Mira; Schmidt, Malthe; Schmiedchen, Brigitta; Wilde, Peer; Schön, Chris-Carolin

2017-10-01

Rye genetic resources provide a valuable source of new alleles for the improvement of frost tolerance in rye breeding programs. Frost tolerance is a must-have trait for winter cereal production in northern and continental cropping areas. Genetic resources should harbor promising alleles for the improvement of frost tolerance of winter rye elite lines. For frost tolerance breeding, the identification of quantitative trait loci (QTL) and the choice of optimum genome-based selection methods are essential. We identified genomic regions involved in frost tolerance of winter rye by QTL mapping in a biparental population derived from a highly frost tolerant selection from the Canadian cultivar Puma and the European elite line Lo157. Lines per se and their testcrosses were phenotyped in a controlled freeze test and in multi-location field trials in Russia and Canada. Three QTL on chromosomes 4R, 5R, and 7R were consistently detected across environments. The QTL on 5R is congruent with the genomic region harboring the Frost resistance locus 2 (Fr-2) in Triticeae. The Puma allele at the Fr-R2 locus was found to significantly increase frost tolerance. A comparison of predictive ability obtained from the QTL-based model with different whole-genome prediction models revealed that besides a few large, also small QTL effects contribute to the genomic variance of frost tolerance in rye. Genomic prediction models assigning a high weight to the Fr-R2 locus allow increasing the selection intensity for frost tolerance by genome-based pre-selection of promising candidates.

Self-Reported Snoring Is Associated with Dyslipidemia, High Total Cholesterol, and High Low-Density Lipoprotein Cholesterol in Obesity: A Cross-Sectional Study from a Rural Area of China.

PubMed

Zhang, Naijin; Chen, Yintao; Chen, Shuang; Jia, Pengyu; Guo, Xiaofan; Sun, Guozhe; Sun, Yingxian

2017-01-17

Studies to explore the relationship between self-reported snoring and dyslipidemia, especially high total cholesterol (TC) and high low-density lipoprotein cholesterol (LDL-C), in the general population are still lacking. Our study was designed to examine whether self-reported snoring is significantly associated with dyslipidemia and ascertain the effects of different snoring intensities on dyslipidemia. There were 10,139 participants in our study. After adjustment for all confounding factors, self-reported snoring (OR = 1.207; p = 0.003), moderate (OR = 1.229; p = 0.015), strong (OR = 1.222; p = 0.033), and very strong (OR = 1.467; p = 0.012) snoring intensity, but not low (OR = 1.110; p = 0.224) snoring intensity, were significantly associated with dyslipidemia among adults with BMI (body mass index) ≥ 25 kg/m². In addition, self-reported snoring was significantly associated with high TC (OR = 1.167; p = 0.048) and high LDL-C (OR = 1.228; p = 0.044), rather than low HDL-C (OR = 1.171; p = 0.057) and high triglyceride (TG) (OR = 1.110; p = 0.141). In conclusion, adults with BMI ≥ 25 kg/m² and who experience snoring, especially moderate, strong, and very strong intensity levels of snoring, should be on the alert regarding the possibility of dyslipidemia, especially high LDL-C and high TC.