Science.gov

Sample records for adiponectin gene polymorphism

  1. Adiponectin gene polymorphisms: Association with childhood obesity

    PubMed Central

    Fraga, Vanêssa Gomes; Gomes, Karina Braga

    2014-01-01

    The current childhood obesity epidemic represents a particular challenge for public health. Understanding of the etiological mechanisms of obesity remains integral in treating this complex disorder. In recent years, studies have elucidated the influence of hormones secreted by adipose tissue named adipokines. Adiponectin is a adipokine that exhibits important anti-inflammatory, insulin-sensitizing and anti-atherogenic properties and it is strongly associated to obesity development. It is well known that adiponectin levels decrease with obesity. Furthermore, studies show that some single nucleotide polymorphisms in the gene encoding adiponectin, ADIPOQ, may influence the expression of this protein. The objective of this paper is to provide an up-to-date review of ADIPOQ polymorphisms in the context of childhood obesity.

  2. Association of Adiponectin Gene Polymorphism with Adiponectin Levels And Risk for Insulin Resistance Syndrome

    PubMed Central

    Prakash, Jai; Mittal, Balraj; Awasthi, Shally; Srivastava, Neena

    2015-01-01

    Background: Adiponectin is an abundant adipose tissue–derived protein with anti-atherogenic, anti-inflammatory and antidiabetic properties. Plasma adiponectin levels are decreased in obesity, type 2 diabetes, and coronary artery disease and low adiponectin levels also predict insulin resistance (IR). Methods: Case-control study in which 642 male and female subjects were participated from the North Indian population. Lipid, insulin, leptin and adiponectin level were estimated using standard protocols by commercially available test kits. Single nucleotide polymorphisms +45T>G and +276G>T of the AMP1 (adiponectin) gene was genotyped by polymerase chain reaction restriction fragment length polymorphism method. Results: Levels of adiponectin, insulin, homeostasis model assessment-IR index (HOMA-IR index), systolic blood pressure and fat mass showed significant differences between male and female subjects. Serum adiponectin level showed highly significant association with both the +45 and the +276 genotypes. The common haplotype triglyceride (TG) showed a significantly lower adiponectin value than other haplotypes (P = 0.0001). A clear trend of decreasing adiponectin levels per copy of the common haplotype was observed. Nonobese insulin sensitive subjects showed a higher adiponectin value (P = 0.0006) than nonobese insulin resistant subjects. The values of blood pressure, adiponectin, insulin, HOMA-IR, total-cholesterol, and low-density lipoprotein-cholesterol significantly associated with TG haplotype. Conclusions: We observed the very strong association of the adiponectin 45-276 genotypes and haplotypes with adiponectin levels in healthy north Indian population and TG haplotypes also associated with metabolic parameters of the IR syndrome. PMID:25949781

  3. Associations of Single Nucleotide Polymorphisms in the Adiponectin Gene with Adiponectin Levels and Cardio-Metabolic Risk Factors in Patients with Cancer

    PubMed Central

    Al Khaldi, Rasha Mazen; Al Mulla, Fahd; Al Awadhi, Shafika; Kapila, Kusum; Mojiminiyi, Olusegun A.

    2011-01-01

    Objectives: The aims of this study are to (1) study the influence of polymorphisms in adiponectin gene on adiponectin levels and potential associations with breast, prostate and colon cancer; (2) investigate the associations of adiponectin levels with other adipokines and breast, prostate and colon cancers. Subjects: We measured fasting adiponectin, leptin, insulin, Sex steroids in 132 (66 females, 66 males) cancer patients and 68 age and sex matched apparently healthy subjects. Body Mass Index (BMI) and waist circumference were used as indices of obesity. Insulin Resistance was assessed using Homeostasis Model Assessment (HOMA). Three single nucleotide polymorphisms (SNP rs182052 (G-10066-A), SNP rs1501299 (276G > T), SNP rs224176 (45T > G) in adiponectin gene were studied using Real Time Polymerase Chain Reaction. Results: GG genotype of SNP rs1501299 was significantly associated with higher levels of adiponectin (OR=1.2, 95%CI(1.03–1.3), p = 0.02); breast (OR=8.6, 95%CI(1.03–71), p = 0.04), colon cancers (OR= 12, 95%CI(1.2–115), p = 0.03). GT genotype was also associated significantly with colon cancer (OR=2.6, 95%CI (1.1–6), p = 0.03). However SNP rs224176 was associated with only breast cancer. Conclusion: Our results demonstrate that adiponectin gene SNP rs1501299 and SNP rs224176 may be the predisposing factors in some cancers but our results differ from what has been reported in other populations suggesting a complex relationship between genetic variations and phenotypic adiponectin levels. PMID:21694446

  4. Single Nucleotide Polymorphism (SNP) in the Adiponectin Gene and Cardiovascular Disease.

    PubMed

    Chirumbolo, Salvatore

    2016-07-01

    Dear Editor, The recent article by Mohammadzadeh et al.[1] on the latest issue of this Journal showed that the T allele +276G/T SNP of ADIPOQ gene is more associated with the increasing risk of coronary artery disease (CAD) in subjects with type 2 diabetes. Adipocytes were described in myocardial tissue of CAD patients and their role recently discussed[2,3]. Susceptibility to CAD by polymorphism in the Q gene of adiponectin has been reported for 3'-UTR, which harbours some genetic loci associated with metabolic risks and atherosclerosis[4]. Actually, previous studies have shown that the haplotype SNP +276G>T was associated with a decreased risk of CAD, after adjustment for potential confounding factors, therefore some controversial opinion still exists[5]. This evidence should be associated with the role exerted by adipocytes and adiponectin in heart physiology. In particular, in hypertensive disorder complicating pregnancy (HDCP), by investigating the population frequency of alleles, genotypes, and haplotypes of two single nucleotide polymorphisms (SNPs), namely +45T>G (rs2241766) and +276G>T (rs1501299), some authors found that the SNP +276 TT genotype was significantly associated with protection against HDCP, when compared to the pooled G genotypes[6]. Moreover, the same +276G/T SNP haplotype was strongly associated with biliary atresia, an intractable neonatal inflammatory and obliterative cholangiopathy, leading to progressive fibrosis and cirrhosis[7]. CAD is closely related to adiponectin biology. The same isoforms of adiponectin seem to be not associated to CAD severity but to glucose metabolism and its impairment[8]. In the paper by Mohammadzadeh et al.[1], T allele in +276G/T SNP haplotype is highly associated with CAD in subjects with type 2 diabetes, but this linkage should be reappraised if related much more to diabetes rather than CAD. Association of T allele in the indicated SNP with CAD may be an indirect consequence of type 2 diabetes, as reported

  5. Association of Adiponectin Gene Polymorphism with Nonalcoholic Fatty Liver Disease in Taiwanese Patients with Type 2 Diabetes

    PubMed Central

    Hsieh, Ching-Jung; Wang, Pei Wen; Hu, Tsung Hui

    2015-01-01

    Objective Patients with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) have a higher prevalence of cardiovascular diseases. In this study we investigated the frequency of single nucleotide polymorphisms (SNPs) of several candidate genes associated with NAFLD in Taiwanese patients with type 2 diabetes mellitus (DM) and NAFLD and in those with DM but without fatty liver disease. Methods We enrolled 350 patients with type 2 DM and NAFLD and 209 patients with DM but without NAFLD. Body mass index (BMI), % body fat (% BF), glycated hemoglobin (HbA1c), high molecular weight (HMW) isoform of adiponectin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels were measured. Thirteen SNPs in 5 genes (adiponectin, leptin, peroxisome proliferator-activated receptor alpha, adiponutrin/patatin-like phospholipase domain-containing protein 3 and peroxisome proliferator-activated receptor γ co-activator 1α ) were measured. Results Only adiponectin rs266729 polymorphism was associated with susceptibility to NAFLD (p = 0.001). Subgroup analysis revealed that the proportion of subjects with homozygous genotype GG was higher in patients with NAFLD (31%) than in controls (11%) and that the proportions of heterozygous CG and homozygous CC were higher in controls (37% and 52%, respectively) than in patients with NAFLD (33% and 36%, respectively). Patients with NAFLD carrying the GG genotype of rs266729 showed significantly lower serum HMW adiponectin levels than patients carrying the GC or CC genotype (3.75±0.37 vs. 3.99±0.66 vs. 4.79±0.58 μg/ml, p< 0.001). Body fat and serum HMW adiponectin levels were the strongest predictors of developing NAFLD (p < 0.001 and 0.004, respectively). Conclusions In patients with type 2 diabetes gene polymorphism of adiponectin rs266729 is associated with risk of NAFLD. G allele of rs266729 is associated with

  6. Lack of evidence for intermolecular epistatic interactions between adiponectin and resistin gene polymorphisms in Malaysian male subjects

    PubMed Central

    Lau, Cia-Hin; Muniandy, Sekaran

    2012-01-01

    Epistasis (gene-gene interaction) is a ubiquitous component of the genetic architecture of complex traits such as susceptibility to common human diseases. Given the strong negative correlation between circulating adiponectin and resistin levels, the potential intermolecular epistatic interactions between ADIPOQ (SNP+45T > G, SNP+276G > T, SNP+639T > C and SNP+1212A > G) and RETN (SNP-420C > G and SNP+299G > A) gene polymorphisms in the genetic risk underlying type 2 diabetes (T2DM) and metabolic syndrome (MS) were assessed. The potential mutual influence of the ADIPOQ and RETN genes on their adipokine levels was also examined. The rare homozygous genotype (risk alleles) of SNP-420C > G at the RETN locus tended to be co-inherited together with the common homozygous genotypes (protective alleles) of SNP+639T > C and SNP+1212A > G at the ADIPOQ locus. Despite the close structural relationship between the ADIPOQ and RETN genes, there was no evidence of an intermolecular epistatic interaction between these genes. There was also no reciprocal effect of the ADIPOQ and RETN genes on their adipokine levels, i.e., ADIPOQ did not affect resistin levels nor did RETN affect adiponectin levels. The possible influence of the ADIPOQ gene on RETN expression warrants further investigation. PMID:22481872

  7. Association of polymorphism in adiponectin (+45 T/G) and leptin (–2548 G/A) genes with type 2 diabetes mellitus in male Egyptians

    PubMed Central

    Motawi, Tarek; Salman, Tarek; Shaker, Olfat

    2015-01-01

    Introduction Adiponectin is an adipose tissue-specific protein with insulin-sensitizing properties. Many investigators have explored the association between adiponectin single nucleotide polymorphisms (SNPs) and type 2 diabetes mellitus (T2DM) in different ethnic populations from different regions. Leptin is a protein hormone constituting an important signal in the regulation of adipose tissue mass and body weight. The aim of this study was to explore potential associations between SNP +45 T>G of the adiponectin gene and SNP 2548G/A of leptin with T2DM and the effect of SNPs on serum adiponectin and leptin levels. Material and methods From the Egyptian population, we enrolled 110 T2DM patients and 90 non-diabetic controls. Serum lipid profile, blood glucose, serum adiponectin, and leptin were measured. Genotyping for two common SNPs of the adiponectin and leptin genes was performed by polymerase chain reaction–restriction fragment length polymorphism. Results The G allele and TG/GG genotype of SNP 45 occurred more frequently than the T allele and TT genotype in T2DM patients compares to the controls. Subjects with the GG + TG genotype of SNP 45 were at increased risk for T2DM (OR = 6.476; 95% CI: 3.401–12.33) and associated with a low serum adiponectin level compared with the TT genotype. The serum leptin concentration of GA + AA genotype carriers was not significantly different from that of the GG genotype in the diabetic group. Conclusions The G allele carriers who have reduced plasma concentrations of adiponectin may have an association with T2DM, while leptin SNP 2548 G/A is not associated with the risk of development of T2DM in the Egyptian population. PMID:26528333

  8. Impacts of Nonsynonymous Single Nucleotide Polymorphisms of Adiponectin Receptor 1 Gene on Corresponding Protein Stability: A Computational Approach

    PubMed Central

    Saleh, Md. Abu; Solayman, Md.; Paul, Sudip; Saha, Moumoni; Khalil, Md. Ibrahim; Gan, Siew Hua

    2016-01-01

    Despite the reported association of adiponectin receptor 1 (ADIPOR1) gene mutations with vulnerability to several human metabolic diseases, there is lack of computational analysis on the functional and structural impacts of single nucleotide polymorphisms (SNPs) of the human ADIPOR1 at protein level. Therefore, sequence- and structure-based computational tools were employed in this study to functionally and structurally characterize the coding nsSNPs of ADIPOR1 gene listed in the dbSNP database. Our in silico analysis by SIFT, nsSNPAnalyzer, PolyPhen-2, Fathmm, I-Mutant 2.0, SNPs&GO, PhD-SNP, PANTHER, and SNPeffect tools identified the nsSNPs with distorting functional impacts, namely, rs765425383 (A348G), rs752071352 (H341Y), rs759555652 (R324L), rs200326086 (L224F), and rs766267373 (L143P) from 74 nsSNPs of ADIPOR1 gene. Finally the aforementioned five deleterious nsSNPs were introduced using Swiss-PDB Viewer package within the X-ray crystal structure of ADIPOR1 protein, and changes in free energy for these mutations were computed. Although increased free energy was observed for all the mutants, the nsSNP H341Y caused the highest energy increase amongst all. RMSD and TM scores predicted that mutants were structurally similar to wild type protein. Our analyses suggested that the aforementioned variants especially H341Y could directly or indirectly destabilize the amino acid interactions and hydrogen bonding networks of ADIPOR1. PMID:27294143

  9. Impacts of Nonsynonymous Single Nucleotide Polymorphisms of Adiponectin Receptor 1 Gene on Corresponding Protein Stability: A Computational Approach.

    PubMed

    Saleh, Md Abu; Solayman, Md; Paul, Sudip; Saha, Moumoni; Khalil, Md Ibrahim; Gan, Siew Hua

    2016-01-01

    Despite the reported association of adiponectin receptor 1 (ADIPOR1) gene mutations with vulnerability to several human metabolic diseases, there is lack of computational analysis on the functional and structural impacts of single nucleotide polymorphisms (SNPs) of the human ADIPOR1 at protein level. Therefore, sequence- and structure-based computational tools were employed in this study to functionally and structurally characterize the coding nsSNPs of ADIPOR1 gene listed in the dbSNP database. Our in silico analysis by SIFT, nsSNPAnalyzer, PolyPhen-2, Fathmm, I-Mutant 2.0, SNPs&GO, PhD-SNP, PANTHER, and SNPeffect tools identified the nsSNPs with distorting functional impacts, namely, rs765425383 (A348G), rs752071352 (H341Y), rs759555652 (R324L), rs200326086 (L224F), and rs766267373 (L143P) from 74 nsSNPs of ADIPOR1 gene. Finally the aforementioned five deleterious nsSNPs were introduced using Swiss-PDB Viewer package within the X-ray crystal structure of ADIPOR1 protein, and changes in free energy for these mutations were computed. Although increased free energy was observed for all the mutants, the nsSNP H341Y caused the highest energy increase amongst all. RMSD and TM scores predicted that mutants were structurally similar to wild type protein. Our analyses suggested that the aforementioned variants especially H341Y could directly or indirectly destabilize the amino acid interactions and hydrogen bonding networks of ADIPOR1. PMID:27294143

  10. Genetic association of adiponectin gene polymorphisms (+45T/G and +10211T/G) with type 2 diabetes in North Indians.

    PubMed

    Saxena, Madhukar; Srivastava, Neena; Banerjee, Monisha

    2012-01-01

    Adiponectin (ADIPOQ) is an abundant protein hormone which belongs to a family of so-called adipokines. It is expressed mostly by adipocytes and is an important regulator of lipid and glucose metabolism. It was shown that decreased serum adiponectin concentration indicated insulin resistance and type 2 diabetes (T2DM) with the risk of cardiovascular complications. The fact that adiponectin is an insulin-sensitizing hormone with anti-diabetic, anti-inflammatory and anti-atherogenic properties, we proposed to study the association of ADIPOQ gene polymorphisms in subjects with T2DM. DNA was isolated from venous blood samples, quantified and subjected to Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) using suitable primers and restriction endonucleases. Adiponectin levels were measured in serum using ELISA. The genotypic, allelic and carriage rate frequencies distribution in patients and controls were analyzed by PSAW software (ver. 17.0). Odd ratios (OR) with 95% confidence interval (CI) were determined to describe the strength of association by logistic regression model. Out of the two polymorphisms studied, +10211T/G showed significant association (P=0.042), the 'G' allele association being highly significant (P=0.022). Further analysis showed that individuals with 'GG' haplotype were at increased risk of T2DM up to 15.5 times [P=0.015, OR (95% CI); 15.558 (1.690-143.174)]. The present study showed that the 'G' allele of ADIPOQ gene (+10211T/G) plays a prominent role with respect to T2DM susceptibility in North-Indian population. PMID:23153972

  11. Variants in the Adiponectin Gene and Serum Adiponectin: The Coronary Artery Development in Young Adults (CARDIA) Study

    PubMed Central

    Wassel, Christina L.; Pankow, James S.; Jacobs, David R.; Steffes, Michael W.; Li, Na; Schreiner, Pamela J.

    2016-01-01

    Circulating adiponectin is involved in the atherosclerotic process and has been associated with cardiovascular disease as well as obesity, insulin resistance, metabolic syndrome, and type 2 diabetes. The adiponectin gene (ADIPOQ) encodes the circulating protein adiponectin and affects its expression. Only a small proportion of all known ADIPOQ polymorphisms have been investigated in relation to circulating adiponectin concentrations. Using data from 3,355 African-American and white men and women aged 33–45 at the year 15 examination from the Coronary Artery Development in Young Adults (CARDIA) Study the association between 10 single-nucleotide polymorphisms (SNPs) within ADIPOQ and serum adiponectin was examined using linear regression. SNPs were chosen based on a tagSNP approach. Models were stratified by self-reported race to control for population stratification, and Bonferroni corrected for multiple comparisons. ADIPOQ SNPs rs17300539 (P < 0.0001), rs182052 (P = 0.0013), rs822393 (P = 0.0005), rs9882205 (P = 0.0001), and rs3774261 (P = 0.0001) were strongly associated with serum adiponectin concentrations in whites. In general, there was a dose–response relationship of adjusted mean adiponectin concentrations across genotypes. Only one SNP, rs17300539 was marginally associated with serum adiponectin concentrations (P = 0.0087) in African Americans. Significant interactions were found between waist and rs182052 (P = 0.0029) and between rs9882505 and smoking (P = 0.001) in whites. Many ADIPOQ SNPs have not yet been examined, and additional studies are needed to determine whether these may be functional variants. PMID:20395949

  12. The Associations of Novel Vitamin D3 Metabolic Gene CYP27A1 Polymorphism, Adiponectin/Leptin Ratio, and Metabolic Syndrome in Middle-Aged Taiwanese Males

    PubMed Central

    Liu, Chia-Chu; Huang, Chun-Nung; Lee, Yung-Chin; Chu, Chih-Sheng; Chang, Chu-Fen; Kuo, Po-Lin; Lai, Wen-Ter

    2015-01-01

    Metabolic syndrome (MetS) confers increased risks of cardiovascular disease (CVD). Both vitamin D3 and adipocytokines (especially adiponectin and leptin) have a great impact on CVD and MetS. In vitamin D3 metabolism, the vitamin D3 25-hydroxylase (CYP27A1) and 25-hydroxyvitamin D3 1-alpha-hydroxylase (CYP27B1) are two key enzymes. This study aimed to examine the influence of vitamin D3 CYP27 single nucleotide polymorphisms (SNPs) on adipocytokines and MetS. Cross-sectional data and DNA samples were collected from male volunteers (n = 649, age: 55.7 ± 4.7 years). Two tagging SNPs, CYP27A1 rs4674344 and CYP27B1 rs10877012, were selected from the HapMap project. MetS was significantly associated with the CYP27A1 rs4674344 SNP (P = 0.04) and the ratio of adiponectin/leptin (A/L ratio) was most correlated to the CYP27A1 rs4674344 SNP, appearing to be significantly lower in T-carriers than in AA subjects (3.7 ± 4.0 versus 5.1 ± 6.0, P = 0.001) and significantly negatively associated after adjustment. For each MetS component associated with the CYP27A1 rs4674344 SNP, the A/L ratios were significantly negative in preclinical stage (condition not meeting the individual criteria), except the blood pressure. In conclusion, CYP27A1 rs4674344 SNP, A/L ratio, and MetS are significantly associated and T-carriers might have a higher risk of developing MetS due to low A/L ratios in the preclinical stage. PMID:25628655

  13. Adiponectin -11377C/G and +276G/T polymorphisms affect adiponectin levels but do not modify responsiveness to therapy in resistant hypertension.

    PubMed

    de Faria, Ana Paula C; Modolo, Rodrigo; Sabbatini, Andréa R; Barbaro, Natália R; Corrêa, Nathália B; Brunelli, Veridiana; Tanus-Santos, José E; Fontana, Vanessa; Moreno, Heitor

    2015-07-01

    Resistant hypertension (RHTN) is a multifactorial and polygenic disease, frequently associated with obesity. Low plasma adiponectin levels, a hormone produced by the adipose tissue, were associated with RHTN. Single nucleotide polymorphisms (SNPs) -11377C/G (rs266729) and +276G/T (rs1501299) in ADIPOQ (adiponectin gene) were associated with hypertension. This study evaluated the association between two SNPs (-11377C/G and +276G/T) and adiponectin levels in RHTN. This study comprised 109 patients with RHTN genotyped for both polymorphisms. A cross-sectional study was designed to compare features of CC homozygous versus G allele carriers for -11377C/G and GG homozygous versus T allele carriers for +276G/T. Office and ambulatory BP measurements were similar among genotypes subgroups in both SNPs as well as the markers of target organ damage (arterial stiffness, left ventricular mass index and microalbuminuria). Adiponectin concentrations were significantly higher in CC compared to G carrier for -11377C/G (CC:7.0 (4.0-10.2) versus G allele:5.5 (2.5-7.9), p = 0.04) and lower in GG compared to T carrier for +276G/T (GG:5.3 (2.3-7.7) versus T allele:7.1 (3.6-10.5), p = 0.04). Adjusting for systolic ambulatory BP, body mass index, age, gender, race and presence of type 2 diabetes, multiple linear regression analyses revealed that the minor alleles G (β-coefficient= -0.14, SE=0.07, p = 0.03) and T (β-coefficient=0.12, SE=0.06, p = 0.04) were independent predictors of adiponectin. The -11377C/G and +276G/T SNPs in ADIPOQ were associated with adiponectin levels in RHTN individuals. PMID:25546819

  14. Association of Adiponectin Polymorphism with Metabolic Syndrome Risk and Adiponectin Level with Stroke Risk: A Meta-Analysis.

    PubMed

    Yuan, Hui-Ping; Sun, Liang; Li, Xing-Hui; Che, Fu-Gang; Zhu, Xiao-Quan; Yang, Fan; Han, Jing; Jia, Chun-Yuan; Yang, Ze

    2016-01-01

    Many previous studies have provided evidence that the ADIPOQ +45T>G polymorphism (rs2241766) might cause metabolic syndrome (MS). As a cardiovascular manifestation of MS, the incidence of stroke is associated with adiponectin; however, the results remain controversial and inconsistent. Systematic searches of relevant studies published up to Dec 2014 and Jan 2016 on the ADIPOQ +45T>G polymorphism and the risk of MS and adiponectin levels and the risk of stroke, respectively, were conducted in MEDLINE and EMBASE. The odds ratio (OR) or risk ratio (RR) and their 95% confidence interval (95% CI) were extracted. Sixteen studies containing 4,113 MS cases and 3,637 healthy controls indicated a weak positive association between ADIPOQ +45 T>G and MS in the dominant genetic model (OR = 1.30, 95% CI = 1.03-1.65), which was also validated by stratified subgroup analyses. Twelve studies including 26,213 participants and 4,246 stroke cases indicated that 5 μg/ml increments in adiponectin level were not relevant to stroke risk (RR = 1.05, 95% CI = 1.00-1.10, P = 0.069). This study suggested a weak positive association of ADIPOQ +45T>G with MS and a strong association with metabolic-related disease. Additionally, adiponectin level was not a causal factor of increasing stroke risk. PMID:27578536

  15. Association of Adiponectin Polymorphism with Metabolic Syndrome Risk and Adiponectin Level with Stroke Risk: A Meta-Analysis

    PubMed Central

    Yuan, Hui-Ping; Sun, Liang; Li, Xing-Hui; Che, Fu-Gang; Zhu, Xiao-Quan; Yang, Fan; Han, Jing; Jia, Chun-Yuan; Yang, Ze

    2016-01-01

    Many previous studies have provided evidence that the ADIPOQ +45T>G polymorphism (rs2241766) might cause metabolic syndrome (MS). As a cardiovascular manifestation of MS, the incidence of stroke is associated with adiponectin; however, the results remain controversial and inconsistent. Systematic searches of relevant studies published up to Dec 2014 and Jan 2016 on the ADIPOQ +45T>G polymorphism and the risk of MS and adiponectin levels and the risk of stroke, respectively, were conducted in MEDLINE and EMBASE. The odds ratio (OR) or risk ratio (RR) and their 95% confidence interval (95% CI) were extracted. Sixteen studies containing 4,113 MS cases and 3,637 healthy controls indicated a weak positive association between ADIPOQ +45 T>G and MS in the dominant genetic model (OR = 1.30, 95% CI = 1.03–1.65), which was also validated by stratified subgroup analyses. Twelve studies including 26,213 participants and 4,246 stroke cases indicated that 5 μg/ml increments in adiponectin level were not relevant to stroke risk (RR = 1.05, 95% CI = 1.00–1.10, P = 0.069). This study suggested a weak positive association of ADIPOQ +45T>G with MS and a strong association with metabolic-related disease. Additionally, adiponectin level was not a causal factor of increasing stroke risk. PMID:27578536

  16. Adiponectin Gene Variants are Associated with Insulin Sensitivity in Response to Dietary Fat Consumption in Caucasian Men

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adiponectin (adipoQ) gene variants have been associated with type 2 diabetes mellitus and insulin resistance. Our aim was to examine whether the presence of several polymorphisms at the adipoQ gene locus (211391 G . A, 211377C.G, 45 T.G, and 276 G.T) influences the insulin sensitivity to dietary fat...

  17. Association of ADIPOQ gene with obesity and adiponectin levels in Malaysian Malays.

    PubMed

    Apalasamy, Yamunah Devi; Rampal, Sanjay; Salim, Agus; Moy, Foong Ming; Bulgiba, Awang; Mohamed, Zahurin

    2014-05-01

    Studies have shown that single-nucleotide polymorphisms (SNPs) on the ADIPOQ gene have been linked with obesity and with adiponectin levels in various populations. Here, we aimed to investigate the association of ADIPOQ rs17366568 and rs3774261 SNPs with obesity and with adiponectin levels in Malaysian Malays. Obesity parameters and adiponectin levels were measured in 574 subjects. Genotyping was performed using real-time polymerase chain reaction and Sequenom MassARRAY. A significant genotypic association was observed between ADIPOQ rs17366568 and obesity. The frequencies of AG and AA genotypes were significantly higher in the obese group (11%) than in the non-obese group (5%) (P=0.024). The odds of A alleles occurring among the obese group were twice those among the non-obese group (odds ratio 2.15; 95% confidence interval 1.13-4.09). However, no significant association was found between allelic frequencies of ADIPOQ rs17366568 and obesity after Bonferroni correction (P>0.025) or between ADIPOQ rs3774261 and obesity both at allelic and genotypic levels. ADIPOQ SNPs were not significantly associated with log-adiponectin levels. GA, GG, and AG haplotypes of the ADIPOQ gene were not associated with obesity. We confirmed the previously reported association of ADIPOQ rs17366568 with the risk of obesity. ADIPOQ SNPs are not important modulators of adiponectin levels in this population. PMID:24449366

  18. Haplotypes and Sequence Variation in the Ovine Adiponectin Gene (ADIPOQ)

    PubMed Central

    An, Qing-Ming; Zhou, Hui-Tong; Hu, Jiang; Luo, Yu-Zhu; Hickford, Jon G. H.

    2015-01-01

    The adiponectin gene (ADIPOQ) plays an important role in energy homeostasis. In this study five separate regions (regions 1 to 5) of ovine ADIPOQ were analysed using PCR-SSCP. Four different PCR-SSCP patterns (A1-D1, A2-D2) were detected in region-1 and region-2, respectively, with seven and six SNPs being revealed. In region-3, three different patterns (A3-C3) and three SNPs were observed. Two patterns (A4-B4, A5-B5) and two and one SNPs were observed in region-4 and region-5, respectively. In total, nineteen SNPs were detected, with five of them in the coding region and two (c.46T/C and c.515G/A) putatively resulting in amino acid changes (p.Tyr16His and p.Lys172Arg). In region-1, -2 and -3 of 316 sheep from eight New Zealand breeds, variants A1, A2 and A3 were the most common, although variant frequencies differed in the eight breeds. Across region-1 and region-3, nine haplotypes were identified and haplotypes A1-A3, A1-C3, B1-A3 and B1-C3 were most common. These results indicate that the ADIPOQ gene is polymorphic and suggest that further analysis is required to see if the variation in the gene is associated with animal production traits. PMID:26610572

  19. Association of adiponectin and adiponectin receptor genes with sow productivity estimated breeding values.

    PubMed

    Jafarikia, Moshen; Méthot, Steve; Maignel, Laurence; Fortin, Frédéric; Wyss, Stefanie; Sullivan, Brian; Palin, Marie-France

    2015-09-01

    Our objectives were to estimate frequencies of previously identified single nucleotide polymorphisms (SNPs) in adiponectin (ADIPOQ) and its receptors (ADIPOR1 and ADIPOR2) in a population of Duroc, Landrace and Yorkshire pigs and evaluate the effect of these alleles on sow productivity estimated breeding values (EBVs). Eight SNPs were genotyped on 446 pigs in the ADIPOQ (c.178G>A, c.*300A>G, c.*1094_1095insC and c.*1779A>C), ADIPOR1 (c.*129A>C) and ADIPOR2 (c.*112G>A, c.*295G>C and c.*1455G>A) genes. Association analyses were performed with sow productivity EBVs based on litter records collected in Canadian breeding farms. There were significant associations between ADIPOQ c.178G>A and c.*1094_1095insC SNPs and studied traits. However, none of these associations remained significant after applying a Bonferroni correction. The ADIPOR2 c.*112G>A SNP was associated with the total number of piglets born (TNB, P < 0.001) and litter weight at weaning (LWW, P < 0.001) EBVs. Associations were also observed between the ADIPOR2 [A;C;G] haplotype and TNB and LWW (P < 0.001). Our results demonstrate that a selection in favor of the c.*112G allele or against the [A;C;G] haplotype may have the potential to increase LWW EBVs. However, the c.*112G allele is also associated with lower TNB EBVs. Some of the alleles of the genes studied showed substantial variability and in general, the results corroborated previously reported findings for an independent sow population. However, careful cost-benefits analyses should be performed before using these markers in selection program as an improvement in TNB may translate into lighter LWW, with its associated negative impact on production traits such as growth performances. PMID:26210991

  20. Investigate the relation between Adiponectin gene variants and cardiovascular comorbidities and diabetes

    PubMed Central

    Eissa, AT.

    2016-01-01

    Objectives This study aimed to study the relationship between the adiponectin gene and coronary artery disease as well as myocardial infarction, hypertension and diabetes in the Saudi population in Riyadh. Methods This was a cohort study of Saudi patients from the Coronary Artery Disease (CAD) registry maintained at King Faisal Specialist Hospital and Research Centre. Samples were genotyped for target Single Nucleotide Polymorphisms (SNPs) by real time polymerase chain reaction (PCR). Furthermore, Chi Square test was used for comparing the variables. Results Out of 860 CAD patients compared with 467 non-CAD. The prevalence of the minor G allele of +45T>G in CAD patients was 934 compared to 786 in controls, and it shows no significant difference (p=0.598) between the two groups. The possibility tested that this variant might be associated with one or more of the CAD risk factors, such as hypertension, myocardial infarction, hypertension and diabetes mellitus. Nevertheless, the study did not show any significance between the two groups in CAD, gender and hypertension. On the other hand, the difference in MI was borderline and significant in diabetes mellitus. Conclusions This study showed a relationship between adiponectin and diabetes only as compared to results from other countries which also showed relationship with coronary artery disease, myocardial infarction and hypertension. PMID:27103900

  1. Obesity-induced DNA hypermethylation of the adiponectin gene mediates insulin resistance

    PubMed Central

    Kim, A. Young; Park, Yoon Jeong; Pan, Xuebo; Shin, Kyung Cheul; Kwak, Soo-Heon; Bassas, Abdulelah F.; Sallam, Reem M.; Park, Kyong Soo; Alfadda, Assim A.; Xu, Aimin; Kim, Jae Bum

    2015-01-01

    Adiponectin plays a key role in the regulation of the whole-body energy homeostasis by modulating glucose and lipid metabolism. Although obesity-induced reduction of adiponectin expression is primarily ascribed to a transcriptional regulation failure, the underlying mechanisms are largely undefined. Here we show that DNA hypermethylation of a particular region of the adiponectin promoter suppresses adiponectin expression through epigenetic control and, in turn, exacerbates metabolic diseases in obesity. Obesity-induced, pro-inflammatory cytokines promote DNMT1 expression and its enzymatic activity. Activated DNMT1 selectively methylates and stimulates compact chromatin structure in the adiponectin promoter, impeding adiponectin expression. Suppressing DNMT1 activity with a DNMT inhibitor resulted in the amelioration of obesity-induced glucose intolerance and insulin resistance in an adiponectin-dependent manner. These findings suggest a critical role of adiponectin gene epigenetic control by DNMT1 in governing energy homeostasis, implying that modulating DNMT1 activity represents a new strategy for the treatment of obesity-related diseases. PMID:26139044

  2. Induction of human adiponectin gene transcription by telmisartan, angiotensin receptor blocker, independently on PPAR-{gamma} activation

    SciTech Connect

    Moriuchi, Akie ||. E-mail: f1195@cc.nagasaki-u-ac.jp; Shimamura, Mika; Kita, Atsushi; Kuwahara, Hironaga; Satoh, Tsuyoshi; Satoh, Tsuyoshi; Fujishima, Keiichiro; Fukushima, Keiko |; Hayakawa, Takao; Mizuguchi, Hiroyuki; Nagayama, Yuji; Kawasaki, Eiji

    2007-05-18

    Adiponectin, an adipose tissue-specific plasma protein, has been shown to ameliorate insulin resistance and inhibit the process of atherosclerosis. Recently, several reports have stated that angiotensin type 1 receptor blockers (ARBs), increase adiponectin plasma level, and ameliorate insulin resistance. Telmisartan, a subclass of ARBs, has been shown to be a partial agonist of the peroxisome proliferator-activated receptor (PPAR)-{gamma}, and to increase the plasma adiponectin level. However, the transcriptional regulation of the human adiponectin gene by telmisartan has not been determined yet. To elucidate the effect of telmisartan on adiponectin, the stimulatory regulation of human adiponectin gene by telmisartan was investigated in 3T3-L1 adipocytes, utilizing adenovirus-mediated luciferase reporter gene-transferring technique. This study indicates that telmisartan may stimulate adiponectin transcription independent of PPAR-{gamma}.

  3. Gene-gene, gene-environment, gene-nutrient interactions and single nucleotide polymorphisms of inflammatory cytokines.

    PubMed

    Nadeem, Amina; Mumtaz, Sadaf; Naveed, Abdul Khaliq; Aslam, Muhammad; Siddiqui, Arif; Lodhi, Ghulam Mustafa; Ahmad, Tausif

    2015-05-15

    Inflammation plays a significant role in the etiology of type 2 diabetes mellitus (T2DM). The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury, oxidative stress and beta cell apoptosis in T2DM. Among the recognized markers are interleukin (IL)-6, IL-1, IL-10, IL-18, tissue necrosis factor-alpha (TNF-α), C-reactive protein, resistin, adiponectin, tissue plasminogen activator, fibrinogen and heptoglobins. Diabetes mellitus has firm genetic and very strong environmental influence; exhibiting a polygenic mode of inheritance. Many single nucleotide polymorphisms (SNPs) in various genes including those of pro and anti-inflammatory cytokines have been reported as a risk for T2DM. Not all the SNPs have been confirmed by unifying results in different studies and wide variations have been reported in various ethnic groups. The inter-ethnic variations can be explained by the fact that gene expression may be regulated by gene-gene, gene-environment and gene-nutrient interactions. This review highlights the impact of these interactions on determining the role of single nucleotide polymorphism of IL-6, TNF-α, resistin and adiponectin in pathogenesis of T2DM. PMID:25987962

  4. Gene-gene, gene-environment, gene-nutrient interactions and single nucleotide polymorphisms of inflammatory cytokines

    PubMed Central

    Nadeem, Amina; Mumtaz, Sadaf; Naveed, Abdul Khaliq; Aslam, Muhammad; Siddiqui, Arif; Lodhi, Ghulam Mustafa; Ahmad, Tausif

    2015-01-01

    Inflammation plays a significant role in the etiology of type 2 diabetes mellitus (T2DM). The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury, oxidative stress and beta cell apoptosis in T2DM. Among the recognized markers are interleukin (IL)-6, IL-1, IL-10, IL-18, tissue necrosis factor-alpha (TNF-α), C-reactive protein, resistin, adiponectin, tissue plasminogen activator, fibrinogen and heptoglobins. Diabetes mellitus has firm genetic and very strong environmental influence; exhibiting a polygenic mode of inheritance. Many single nucleotide polymorphisms (SNPs) in various genes including those of pro and anti-inflammatory cytokines have been reported as a risk for T2DM. Not all the SNPs have been confirmed by unifying results in different studies and wide variations have been reported in various ethnic groups. The inter-ethnic variations can be explained by the fact that gene expression may be regulated by gene-gene, gene-environment and gene-nutrient interactions. This review highlights the impact of these interactions on determining the role of single nucleotide polymorphism of IL-6, TNF-α, resistin and adiponectin in pathogenesis of T2DM. PMID:25987962

  5. Placental adiponectin gene DNA methylation levels are associated with mothers' blood glucose concentration.

    PubMed

    Bouchard, Luigi; Hivert, Marie-France; Guay, Simon-Pierre; St-Pierre, Julie; Perron, Patrice; Brisson, Diane

    2012-05-01

    Growing evidence suggests that epigenetic profile changes occurring during fetal development in response to in utero environment variations could be one of the mechanisms involved in the early determinants of adult chronic diseases. In this study, we tested whether maternal glycemic status is associated with the adiponectin gene (ADIPOQ) DNA methylation profile in placenta tissue, in maternal circulating blood cells, and in cord blood cells. We found that lower DNA methylation levels in the promoter of ADIPOQ on the fetal side of the placenta were correlated with higher maternal glucose levels during the second trimester of pregnancy (2-h glucose after the oral glucose tolerance test; r(s) ≤ -0.21, P < 0.05). Lower DNA methylation levels on the maternal side of the placenta were associated with higher insulin resistance index (homeostasis model assessment of insulin resistance) during the second and third trimesters of pregnancy (r(s) ≤ -0.27, P < 0.05). Finally, lower DNA methylation levels were associated with higher maternal circulating adiponectin levels throughout pregnancy (r(s) ≤ -0.26, P < 0.05). In conclusion, the ADIPOQ DNA methylation profile was associated with maternal glucose status and with maternal circulating adiponectin concentration. Because adiponectin is suspected to have insulin-sensitizing proprieties, these epigenetic adaptations have the potential to induce sustained glucose metabolism changes in the mother and offspring later in life. PMID:22396200

  6. Association of Atherosclerotic Peripheral Arterial Disease with Adiponectin Genes SNP+45 and SNP+276: A Case-Control Study

    PubMed Central

    Gherman, Claudia D.; Bolboacă, Sorana D.

    2013-01-01

    Objectives. We hypothesized that adiponectin gene SNP+45 (rs2241766) and SNP+276 (rs1501299) would be associated with atherosclerotic peripheral arterial disease (PAD). Furthermore, the association between circulating adiponectin levels, fetuin-A, and tumoral necrosis factor-alpha (TNF-α) in patients with atherosclerotic peripheral arterial disease was investigated. Method. Several blood parameters (such as adiponectin, fetuin-A, and TNF-α) were measured in 346 patients, 226 with atherosclerotic peripheral arterial disease (PAD) and 120 without symptomatic PAD (non-PAD). Two common SNPs of the ADIPOQ gene represented by +45T/G 2 and +276G/T were also investigated. Results. Adiponectin concentrations showed lower circulating levels in the PAD patients compared to non-PAD patients (P < 0.001). Decreasing adiponectin concentration was associated with increasing serum levels of fetuin-A in the PAD patients. None of the investigated adiponectin SNPs proved to be associated with the subjects' susceptibility to PAD (P > 0.05). Conclusion. The results of our study demonstrated that neither adiponectin SNP+45 nor SNP+276 is associated with the risk of PAD. PMID:23819115

  7. Genetic polymorphisms in obesity-related genes and endometrial cancer risk

    PubMed Central

    Chen, Xiaoli; Xiang, Yong-Bing; Long, Ji-Rong; Cai, Hui; Cai, Qiuyin; Cheng, Jiarong; Wen, Wanqing; Gao, Yu-Tang; Zheng, Wei; Shu, Xiao-Ou

    2011-01-01

    Background Obesity is associated with circulating levels of adiponectin and leptin and endometrial cancer risk. Little is known about whether single nucleotide polymorphisms (SNPs) in the genes that encode adiponectin (ADIPOQ), leptin (LEP), adiponectin receptor 1 (ADIPOR1), adiponectin receptor 2 (ADIPOR2), and leptin receptor (LEPR) are associated with endometrial cancer. Methods We selected 87 tagging SNPs to capture common genetic variants in these five genes. These SNPs were evaluated in 1,028 endometrial cancer cases and 1,932 community controls recruited from Chinese women. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Results Three of the 10 SNPs evaluated in the ADIPOQ gene were significantly associated with reduced cancer risk. The OR for women homozygous for the minor allele (A/A) for rs3774262 was 0.68 (95% CI: 0.48-0.97) compared with women homozygous for the major allele (G/G). Similar results were found for SNPs rs1063539 and rs12629945 in ADIPOQ, which were in linkage disequilibrium with rs3774262. These associations became non-significant after Bonferroni correction was applied. Controls with the minor allele A at rs3774262 had lower weight, waist circumference, hip circumference, and BMI than controls with the major allele G (all P<0.05). Women homozygous for the minor allele (T/T) of rs2071045 in the LEP gene also had significantly lower risk (OR=0.70 (0.54-0.90)) than women homozygous for the major allele (C/C). No other SNPs in the LEP, ADIPOR1, ADIPOR2, or LEPR genes were found to be associated with cancer risk. Conclusions Although a chance finding cannot be ruled out, the consistency of findings for gene-endometrial cancer risk and gene-obesity measurements suggests that genetic polymorphisms in the ADIPOQ genes may play a role in endometrial cancer development. PMID:22038736

  8. Gene polymorphisms and chronic obstructive pulmonary disease

    PubMed Central

    Wu, Xiaodan; Yuan, Bowei; López, Elena; Bai, Chunxue; Wang, Xiangdong

    2014-01-01

    The genetic component was suggested to contribute to the development of chronic obstructive pulmonary disease (COPD), a major and growing public health burden. The present review aims to characterize the evidence that gene polymorphisms contribute to the aetiology of COPD and related traits, and explore the potential relationship between certain gene polymorphisms and COPD susceptibility, severity, lung function, phenotypes, or drug effects, even though limited results from related studies lacked consistency. Most of these studies were association studies, rather than confirmatory studies. More large-sized and strictly controlled studies are needed to prove the relationship between gene polymorphisms and the reviewed traits. More importantly, prospective confirmatory studies beyond initial association studies will be necessary to evaluate true relationships between gene polymorphisms and COPD and help individualized treatment for patients with COPD. PMID:24256364

  9. Gene molecular analysis and Adiponectin expression in professional Water Polo players.

    PubMed

    Nigro, Ersilia; Sangiorgio, Dino; Scudiero, Olga; Monaco, Maria Ludovica; Polito, Rita; Villone, Giovanni; Daniele, Aurora

    2016-05-01

    Metabolic Syndrome prevalence has reaching epidemic proportions worldwide. Adiponectin (Acrp30), and in particular its High Molecular Weight (HMW) oligomers, contributes to enhance insulin sensitivity and to reduce inflammation levels. Physical exercise improves body's biochemical balance and metabolism resulting effective in prevention of metabolic diseases. Whether improvement of metabolic features mediated by physical exercise is associated with changes in Acrp30 serum composition is not yet clarified. In the present study, we investigated total Acrp30 expression, its oligomeric status and genetic variants in adiponectin gene (ACDC) in twenty-two professional Water Polo (WP) Players and 40 age- and sex-matched controls. Anthropometric, metabolic parameters and total Acrp30 were assessed; Acrp30 oligomeric profile was characterized by Western blot as well as by FPLC analysis. ACDC gene was analyzed by direct-sequencing analysis. Significant elevated body mass index, aspartate aminotransferase and lactate dehydrogenase levels and, conversely, significantly lower concentrations of total and cholesterol low density lipoprotein were present in WP players. No significant difference was found in total Acrp30 and/or HMW oligomers. Interestingly, in WP players, a direct relationship between total Acrp30 and monocytes as well as an inverse relationship between total Acrp30 and AST levels were found. ACDC screening revealed previously described SNPs. In conclusion, our study confirms the long-term beneficial effects of high physical training on metabolism and suggests that they are not associated with Acrp30 and/or HMW oligomers changes. Moreover, the correlation of Acrp30 with monocytes in WP athletes could represent a mechanism by which Acrp30 participates in exercise-induced anti-inflammatory functions and/or cardiovascular health. PMID:26970705

  10. Adiponectin, a downstream target gene of peroxisome proliferator-activated receptor {gamma}, controls hepatitis B virus replication

    SciTech Connect

    Yoon, Sarah; Jung, Jaesung; Kim, Taeyeung; Park, Sun; Chwae, Yong-Joon; Shin, Ho-Joon; Kim, Kyongmin

    2011-01-20

    In this study, HepG2-hepatitis B virus (HBV)-stable cells that did not overexpress HBx and HBx-deficient mutant-transfected cells were analyzed for their expression of HBV-induced, upregulated adipogenic and lipogenic genes. The mRNAs of CCAAT enhancer binding protein {alpha} (C/EBP{alpha}), peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}), adiponectin, liver X receptor {alpha} (LXR{alpha}), sterol regulatory element binding protein 1c (SREBP1c), and fatty acid synthase (FAS) were expressed at higher levels in HepG2-HBV and lamivudine-treated stable cells and HBx-deficient mutant-transfected cells than in the HepG2 cells. Lamivudine treatment reduced the mRNA levels of PPAR{gamma} and C/EBP{alpha}. Conversely, HBV replication was upregulated by adiponectin and PPAR{gamma} agonist rosiglitazone treatments and was downregulated by adiponectin siRNAs. Collectively, our results demonstrate that HBV replication and/or protein expression, even in the absence of HBx, upregulated adipogenic or lipogenic genes, and that the control of adiponectin might prove useful as a therapeutic modality for the treatment of chronic hepatitis B.

  11. [Relationship of MTHFR gene polymorphisms with infertility].

    PubMed

    Guo, Kai-min; Tian, Run-hui; Wang, Hong-liang

    2016-02-01

    The folate metabolic pathway plays important roles in cellular physiology by participating in nucleotide synthesis, DNA repair and methylation, and maintenance and stability of the genome. Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme involved in folate metabolism. Polymorphisms of MTHFR may change the level of homocysteine and affect DNA synthesis and methylation, leading to an increased oxidative stress and disturbed methylation reactions and consequently affecting reproductive function. This article presents an overview on MTHFR gene polymorphisms, proposing that multicentered, large-sample and long-term prospective studies are needed to reveal the relationship between MTHFR gene polymorphisms and infertility. PMID:26939404

  12. Glycidamide genotoxicity modulated by Caspases genes polymorphisms.

    PubMed

    de Lima, João Pereira; Silva, Susana N; Rueff, José; Pingarilho, Marta

    2016-08-01

    Acrylamide (AA) is amongst acknowledged carcinogenic dietary factors. Its DNA-reactive metabolite is glycidamide (GA). The present study intended to correlate the role of key polymorphic genes of apoptosis (CASP7, CASP8, CASP9, CASP10, LTA and TNFRSF1B) with biomarkers of effect of DNA damage, namely the sister chromatid exchange assay (SCE) and the comet assay in whole blood cells exposed to GA. The aim was to assess as a proof of concept the role that pro-apoptotic effector proteins might have in the yields of genotoxic effects when those effector proteins are coded by polymorphic genes. Whole blood from a small group of volunteers was exposed to GA to assess DNA damage and the volunteers were genotyped for polymorphic genes related to apoptosis pathways. A relation between the induction of SCE and several variants of the polymorphism CASP8 rs1035142 G>T was observed. Also, a relation between the % tail DNA and the CASP10 I522L polymorphism was found. Furthermore, associations between % tail DNA and several SNP-SNP interactions of CASP8 and CASP10 were found. A possible correlation between DNA damage and the genetic susceptibility, bestowed by polymorphic genes in the apoptosis inducing pathways was verified. PMID:27062911

  13. The Adiponectin Variants Contribute to the Genetic Background of Type 2 Diabetes in Turkish Population.

    PubMed

    Arikoglu, Hilal; Ozdemir, Hulya; Kaya, Dudu Erkoc; Ipekci, Suleyman Hilmi; Arslan, Ahmet; Kayis, Seyit Ali; Gonen, Mustafa Sait

    2013-10-26

    Adiponectin, an adipose tissue specific protein encoded by the Adiponectin gene, modulates insulin sensitivity and plays an important role in regulating energy homeostasis. Many studies have shown that single nucleotide polymorphisms (SNPs) in the Adiponectin gene are associated with low plasma adiponectin levels, insulin resistance and an increased risk of type 2 diabetes mellitus. The aim of the present study was to evaluate the contribution of the Adiponectin gene polymorphisms in genetic background of type 2 diabetes in a Turkish population. In total, 169 unrelated and non-obese diabetic patients and 119 age- and BMI-matched non-diabetic individuals with no family history of diabetes were enrolled in this study. We detected a significant association between type 2 diabetes and two SNPs: SNP -11391G>A, which is located in the promoter region of the Adiponectin gene, and SNP +276G>T, which is found in intron 2 of the gene (P<0.05). The silence SNP G15G (+45T>G) in exon 1 and SNP +349A>G in intron 2 also showed a weak association with type 2 diabetes (P=0.06 and P=0.07, respectively), while SNPs -3971A>G in intron 1 and Y111H, R112C and H241P in exon 3 showed no association (P>0.05). In conclusion, these findings suggest that Adiponectin gene polymorphisms might be effective on susceptibility for type 2 diabetes development which emerged from the interactions between multiple genes, variants and environmental factors. PMID:24513330

  14. Adiponectin stimulates IL-8 production by rheumatoid synovial fibroblasts

    SciTech Connect

    Kitahara, Kanako; Kusunoki, Natsuko; Kakiuchi, Terutaka; Suguro, Toru; Kawai, Shinichi

    2009-01-09

    The adipokines are linked not only to metabolic regulation, but also to immune responses. Adiponectin, but not leptin or resistin induced interleukin-8 production from rheumatoid synovial fibroblasts (RSF). The culture supernatant of RSF treated with adiponectin induced chemotaxis, although adiponectin itself had no such effect. Addition of antibody against adiponectin, and inhibition of adiponectin receptor gene decreased adiponectin-induced IL-8 production. Nuclear translocation of nuclear factor-kappa B was increased by adiponectin. The induction of interleukin-8 was inhibited by mitogen-activated protein kinase inhibitors. These findings suggest that adiponectin contributes to the pathogenesis of rheumatoid arthritis.

  15. Single nucleotide polymorphisms in caprine calpastatin gene.

    PubMed

    Sharma, R; Maitra, A; Pandey, A K; Singh, L V; Mishra, B P

    2013-04-01

    The calpains and calpastatin (CAST) make up a major cytosolic proteolytic system, the calpain-calpastatin system, found in mammalian tissues. The relative levels of the components of the calpain-calpastatin system determine the extent of meat tenderization during postmortem storage. Calpastatin (CAST) is a protein inhibitor of the ubiquitous calcium-dependent proteases-micro-calpain and m-calpain. Polymorphisms in the bovine, ovine and pig CAST gene have been associated with meat tenderness but little is known about how caprine CAST gene may affect goat meat quality traits. In this study we selected different parts of the CAST gene: 1) that have been previously reported to be polymorphic, intron 5 and 12 and 3'UTR; 2) first time explored (exon 3, 7 and 8 and part of intron 7 and 8) to investigate polymorphic status of caprine CAST gene. Using comparative sequencing ten novel SN Ps located in exon 3 and intron 5, 7 and 8 were identified. Previously reported SNPs in intron 5, 3'UTR and intron 12 were absent. Sequence analysis revealed a non synonymous amino acid variation in exon 3, which would result in Lys/Arg substitution in the corresponding protein sequence. Considerable variation was detected in intronic regions. Twenty-four InDel were also recognized in intronic regions (15) and 3'UTR (9). All the sequences shared high homology with published bovine and ovine sequences. Three PCR-RFLP loci have been established for further analyzing genetic polymorphism in indigenous goats. PMID:23866627

  16. The extensive polymorphism of KIR genes

    PubMed Central

    Middleton, Derek; Gonzelez, Faviel

    2010-01-01

    The functions of human natural killer (NK) cells are controlled by diverse families of antigen receptors. Prominent among these are the killer cell immunoglobulin-like receptors (KIR), a family of genes clustered in one of the most variable regions of the human genome. Within this review we discuss the vast polymorphism of the KIR gene complex which rivals that of the human leucocyte antigen (HLA) complex. There are several aspects to this polymorphism. Initially there is presence/absence of individual KIR genes, with four of these genes, termed framework genes, being present in all individuals tested to date, except on those very occasional instances when the gene has been deleted. Within each gene, alleles are present at different frequencies. We provide details of a new website that enables convenient searching for data on KIR gene, allele and genotype frequencies in different populations and show how these frequencies vary in different worldwide populations and the high probability of individuals differing in their KIR repertoire when both gene and allele polymorphism is considered. The KIR genes present in an individual may be classified into A and/or B haplotypes, which respectively have a more inhibitory role or a more activating role on the function of the NK cell. Family studies have been used to ascertain the make-up of these haplotypes, inclusion of allele typing enabling determination of whether one or two copies of a particular gene is present. In addition to genetic diversification the KIR gene complex shows differences at the functional level with different alleles having different protein expression levels and different avidity with their HLA ligand. PMID:20028428

  17. Association of Apolipoprotein B and Adiponectin Receptor 1 Genes with Carcass, Bone Integrity and Performance Traits in a Paternal Broiler Line.

    PubMed

    da Cruz, Valdecy Aparecida Rocha; Schenkel, Flávio Schramm; Savegnago, Rodrigo Pelicioni; Grupioni, Natalia Vinhal; Stafuzza, Nedenia Bonvino; Sargolzaei, Mehdi; Ibelli, Adriana Mércia Guaratini; Peixoto, Jane de Oliveira; Ledur, Mônica Corrêa; Munari, Danísio Prado

    2015-01-01

    Apolipoprotein B (APOB) and Adiponectin Receptor 1 (ADIPOR1) are related to the regulation of feed intake, fat metabolism and protein deposition and are candidate genes for genomic studies in birds. In this study, associations of two single nucleotide polymorphisms (SNPs) g.102A>T (APOB) and g.729C>T (ADIPOR1) with carcass, bone integrity and performance traits in broilers were investigated. Genotyping was performed on a paternal line of 1,454 broilers. The SNP detection was carried out by PCR-RFLP technique using the restriction enzymes HhaI for the SNP g.729C>T and MslI for the SNP g.102A>T. The association analyses of the two SNPs with 85 traits were performed using the restricted maximum likelihood (REML) and Generalized Quasi-Likelihood Score (GQLS) methods. For REML the model included the random additive genetic effect of animal and fixed effects of sex, hatch and SNP genotypes. In the GQLS method, a logistic regression was used to associate the genotypes with phenotypes adjusted for fixed effects of sex and hatch. The SNP g.729C>T in the ADIPOR1 gene was associated with thickness of the femur and breast skin yield. Thus, the ADIPOR1 gene seems implicated in the metabolism and/or fat deposition and bone integrity in broilers. PMID:26322976

  18. Association of Apolipoprotein B and Adiponectin Receptor 1 Genes with Carcass, Bone Integrity and Performance Traits in a Paternal Broiler Line

    PubMed Central

    da Cruz, Valdecy Aparecida Rocha; Schenkel, Flávio Schramm; Savegnago, Rodrigo Pelicioni; Grupioni, Natalia Vinhal; Stafuzza, Nedenia Bonvino; Sargolzaei, Mehdi; Ibelli, Adriana Mércia Guaratini; Peixoto, Jane de Oliveira; Ledur, Mônica Corrêa; Munari, Danísio Prado

    2015-01-01

    Apolipoprotein B (APOB) and Adiponectin Receptor 1 (ADIPOR1) are related to the regulation of feed intake, fat metabolism and protein deposition and are candidate genes for genomic studies in birds. In this study, associations of two single nucleotide polymorphisms (SNPs) g.102A>T (APOB) and g.729C>T (ADIPOR1) with carcass, bone integrity and performance traits in broilers were investigated. Genotyping was performed on a paternal line of 1,454 broilers. The SNP detection was carried out by PCR-RFLP technique using the restriction enzymes HhaI for the SNP g.729C>T and MslI for the SNP g.102A>T. The association analyses of the two SNPs with 85 traits were performed using the restricted maximum likelihood (REML) and Generalized Quasi-Likelihood Score (GQLS) methods. For REML the model included the random additive genetic effect of animal and fixed effects of sex, hatch and SNP genotypes. In the GQLS method, a logistic regression was used to associate the genotypes with phenotypes adjusted for fixed effects of sex and hatch. The SNP g.729C>T in the ADIPOR1 gene was associated with thickness of the femur and breast skin yield. Thus, the ADIPOR1 gene seems implicated in the metabolism and/or fat deposition and bone integrity in broilers. PMID:26322976

  19. IL-10 gene polymorphism and herpesvirus infections.

    PubMed

    Hurme, M; Haanpää, M; Nurmikko, T; Wang, X-Y; Virta, M; Pessi, T; Kilpinen, S; Hulkkonen, J; Helminen, M

    2003-01-01

    Genetics has an important role in resistance to various infections and it also may modify the clinical picture of an infectious disease. Here, we briefly review our recent data demonstrating that the polymorphism of the IL-10 gene is associated with resistance to some common herpesviruses and, additionally, that this same gene is involved in the regulation of the severity of the infection and in the reactivation process. PMID:12627487

  20. Combined delivery of the adiponectin gene and rosiglitazone using cationic lipid emulsions.

    PubMed

    Davaa, Enkhzaya; Kang, Bong-Seok; Han, Joo-Hui; Lee, Sang-Eun; Ng, Choon Lian; Myung, Chang-Seon; Park, Jeong-Sook

    2015-04-10

    For the combined delivery of an insulin-sensitizing adipokine; i.e., the ADN gene, and the potent PPARγ agonist rosiglitazone, cationic lipid emulsions were formulated using the cationic lipid DOTAP, helper lipid DOPE, castor oil, Tween 20 and Tween 80. The effect of drug loading on the physicochemical characteristics of the cationic emulsion/DNA complexes was investigated. Complex formation between the cationic emulsion and negatively charged plasmid DNA was confirmed and protection from DNase was observed. The in vitro transfection efficiency and cytotoxicity were evaluated in HepG2 cells. The particle sizes of the cationic emulsion/DNA complex were in the range 230-540 nm and those of the rosiglitazone-loaded cationic emulsion/DNA complex were in the range 220-340 nm. Gel retardation of the complexes was observed when the complexation weight ratios of the cationic lipid to plasmid DNA exceeded 4:1 for both the drug-free and rosiglitazone-loaded complexes. Both complexes stabilized plasmid DNA against DNase. The ADN expression level increased dose-dependently when cells were transfected with the cationic emulsion/DNA complexes. The rosiglitazone-loaded cationic emulsion/DNA complexes showed higher cellular uptake in HepG2 cells depending on the rosiglitazone loading, but not depending on the type of plasmid DNA type such as pVAX/ADN, pCAG/ADN, or pVAX. The drug-loaded cationic emulsion/plasmid DNA complexes were less cytotoxic than free rosiglitazone. Therefore, a cationic emulsion could potentially serve as a co-delivery system for rosiglitazone and the adiponectin gene. PMID:25681724

  1. Innate Immune Gene Polymorphisms in Tuberculosis

    PubMed Central

    Sadee, Wolfgang

    2012-01-01

    Tuberculosis (TB) is a leading cause worldwide of human mortality attributable to a single infectious agent. Recent studies targeting candidate genes and “case-control” association have revealed numerous polymorphisms implicated in host susceptibility to TB. Here, we review current progress in the understanding of causative polymorphisms in host innate immune genes associated with TB pathogenesis. We discuss genes encoding several types of proteins: macrophage receptors, such as the mannose receptor (MR, CD206), dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN, CD209), Dectin-1, Toll-like receptors (TLRs), complement receptor 3 (CR3, CD11b/CD18), nucleotide oligomerization domain 1 (NOD1) and NOD2, CD14, P2X7, and the vitamin D nuclear receptor (VDR); soluble C-type lectins, such as surfactant protein-A (SP-A), SP-D, and mannose-binding lectin (MBL); phagocyte cytokines, such as tumor necrosis factor (TNF), interleukin-1β (IL-1β), IL-6, IL-10, IL-12, and IL-18; chemokines, such as IL-8, monocyte chemoattractant protein 1 (MCP-1), RANTES, and CXCL10; and other important innate immune molecules, such as inducible nitric oxide synthase (iNOS) and solute carrier protein 11A1 (SLC11A1). Polymorphisms in these genes have been variably associated with susceptibility to TB among different populations. This apparent variability is probably accounted for by evolutionary selection pressure as a result of long-term host-pathogen interactions in certain regions or populations and, in part, by lack of proper study design and limited knowledge of molecular and functional effects of the implicated genetic variants. Finally, we discuss genomic technologies that hold promise for resolving questions regarding the evolutionary paths of the human genome, functional effects of polymorphisms, and corollary impacts of adaptation on human health, ultimately leading to novel approaches to controlling TB. PMID:22825450

  2. Glucosyltransferase gene polymorphism among Streptococcus mutans strains.

    PubMed Central

    Chia, J S; Hsu, T Y; Teng, L J; Chen, J Y; Hahn, L J; Yang, C S

    1991-01-01

    Genetic polymorphisms in genes coding for the glucosyltransferases were detected among Streptococcus mutans serotype c strains by Southern blot analysis with DNA probes located within the gtfB gene (H. Aoki, T. Shiroza, M. Hayakawa, S. Sato, and H. K. Kuramitsu, Infect. Immun. 53:587-594, 1986). Restriction endonucleases were used to examine genomic DNAs isolated from serotype a to h strains. The variations were readily detected among 33 strains of serotype c by EcoRI and PstI restriction enzyme digestions. Serotypes e and f, which are genetically similar to serotype c, also had comparable polymorphism; however, serotypes a, b, d, g, and h did not hybridize to the same DNA probes in parallel experiments. Further analysis of enzymatic activities for glucan synthesis and sucrose-dependent adherence revealed no significant differences among the serotype c strains. Our results suggested that genetic polymorphisms existing in S. mutans serotype c strains may reflect a complexity in genes coding for the glucosyltransferases, which are produced ubiquitously in members of the S. mutans group. Images PMID:1826894

  3. The prevention and treatment of hypoadiponectinemia-associated human diseases by up-regulation of plasma adiponectin.

    PubMed

    Hossain, Md Murad; Mukheem, Abdul; Kamarul, Tunku

    2015-08-15

    Hypoadiponectinemia is characterized by low plasma adiponectin levels that can be caused by genetic factors, such as single nucleotide polymorphisms (SNPs) and mutations in the adiponectin gene or by visceral fat deposition/obesity. Reports have suggested that hypoadiponectinemia is associated with dyslipidemia, hypertension, hyperuricemia, metabolic syndrome, atherosclerosis, type 2 diabetes mellitus and various cardiovascular diseases. Previous studies have highlighted several potential strategies to up-regulate adiponectin secretion and function, including visceral fat reduction through diet therapy and exercise, administration of exogenous adiponectin, treatment with peroxisome proliferator-activating receptor gamma (PPARγ) agonists (e.g., thiazolidinediones (TZDs)) and ligands (e.g., bezafibrate and fenofibrate) or the blocking of the renin-angiotensin system. Likewise, the up-regulation of the expression and stimulation of adiponectin receptors by using adiponectin receptor agonists would be an effective method to treat obesity-related conditions. Notably, adiponectin is an abundantly expressed bioactive protein that also exhibits a wide spectrum of biological properties, such as insulin-sensitizing, anti-diabetic, anti-inflammatory and anti-atherosclerotic activities. Although targeting adiponectin and its receptors has been useful for treating diabetes and other metabolic-related diseases in experimental studies, current drug development based on adiponectin/adiponectin receptors for clinical applications is scarce, and there is a lack of available clinical trial data. This comprehensive review discusses the strategies that are presently being pursued to harness the potential of adiponectin up-regulation. In addition, we examined the current status of drug development and its potential for clinical applications. PMID:25818192

  4. Androgen receptor gene polymorphism in zebra species

    PubMed Central

    Ito, Hideyuki; Langenhorst, Tanya; Ogden, Rob; Inoue-Murayama, Miho

    2015-01-01

    Androgen receptor genes (AR) have been found to have associations with reproductive development, behavioral traits, and disorders in humans. However, the influence of similar genetic effects on the behavior of other animals is scarce. We examined the loci AR glutamine repeat (ARQ) in 44 Grevy's zebras, 23 plains zebras, and three mountain zebras, and compared them with those of domesticated horses. We observed polymorphism among zebra species and between zebra and horse. As androgens such as testosterone influence aggressiveness, AR polymorphism among equid species may be associated with differences in levels of aggression and tameness. Our findings indicate that it would be useful to conduct further studies focusing on the potential association between AR and personality traits, and to understand domestication of equid species. PMID:26236645

  5. Differential Associations between CDH13 Genotypes, Adiponectin Levels, and Circulating Levels of Cellular Adhesive Molecules

    PubMed Central

    Teng, Ming-Sheng; Wu, Semon; Hsu, Lung-An; Chou, Hsin-Hua; Ko, Yu-Lin

    2015-01-01

    CDH13 gene variants with lower adiponectin levels are paradoxically associated with a more favorable metabolic profile. We investigated the statistical association between CDH13 locus variants and adiponectin levels by examining 12 circulating inflammation marker levels and adiposity status in 530 Han Chinese people in Taiwan. After adjustments for clinical covariates, adiponectin levels were positively associated with soluble vascular cell adhesion molecule-1 (sVCAM1) levels and negatively associated with adiposity status and levels of C-reactive protein (CRP), soluble E-selectin (sE-selectin), and soluble intercellular adhesion molecule-1 (sICAM1). In addition, minor alleles of the CDH13 rs12051272 polymorphism were found to have lower adiponectin levels and higher CRP, sE-selectin, sICAM1, and sVCAM1 levels as well as higher body mass indices and waist circumferences in participants (all P < 0.05). In a subgroup analysis stratified by sex, significant associations between CDH13 genotypes and sE-selectin levels occurred only in men (P = 3.9 × 10−4 and interaction P = 0.005). CDH13 locus variants and adiponectin levels are associated with circulating levels of cellular adhesion molecules and adiposity status in a differential manner that interacts with sex. These results provide further evidence for the crucial role of adiponectin levels and CDH13 gene variants in immune-mediated and inflammatory diseases. PMID:26600672

  6. Interleukin-1 gene polymorphisms and toxoplasmic retinochoroiditis

    PubMed Central

    Moreira, Paula R.; Costa, Germano C.; Dutra, Walderez O.; Oréfice, Fernando; Teixeira, Antônio L.

    2008-01-01

    Purpose It has been proposed that cytokine gene polymorphisms can predispose individuals to disease by enhancing inflammatory processes. Considering the relevance of interleukin-1 (IL-1) in the pathogenesis of toxoplasmic retinochoroiditis (TR), we investigated whether IL1A −889 C/T and IL1B +3954C/T promoter polymorphisms are associated with TR in humans. Methods We performed a cross-sectional study that involved 100 Brazilian TR patients and 100 age- and gender-matched control subjects. Genomic DNA was obtained from oral swabs of all participants and amplified using polymerase chain reaction (PCR) with specific primers flanking the locus −889 of IL1A and +3954 of IL1B. PCR products were submitted to digestion and analyzed by PAGE to distinguish C and T alleles. Results There was no significant difference in the genotype or allele distributions of the IL1A −889 C/T and IL1B +3954C/T polymorphisms in patients with TR when compared with controls. However, in a subgroup analysis, the frequency of genotype and allele distributions of IL1A −889 C/T differed significantly between TR patients with and without recurrent episodes. Conclusion This study suggests that the genotypes related with a high production of IL-1a may be associated with the recurrence of TR. PMID:18941541

  7. Gene Polymorphism Studies in a Teaching Laboratory

    NASA Astrophysics Data System (ADS)

    Shultz, Jeffry

    2009-02-01

    I present a laboratory procedure for illustrating transcription, post-transcriptional modification, gene conservation, and comparative genetics for use in undergraduate biology education. Students are individually assigned genes in a targeted biochemical pathway, for which they design and test polymerase chain reaction (PCR) primers. In this example, students used genes annotated for the steroid biosynthesis pathway in soybean. The authoritative Kyoto encyclopedia of genes and genomes (KEGG) interactive database and other online resources were used to design primers based first on soybean expressed sequence tags (ESTs), then on ESTs from an alternate organism if soybean sequence was unavailable. Students designed a total of 50 gene-based primer pairs (37 soybean, 13 alternative) and tested these for polymorphism state and similarity between two soybean and two pea lines. Student assessment was based on acquisition of laboratory skills and successful project completion. This simple procedure illustrates conservation of genes and is not limited to soybean or pea. Cost per student estimates are included, along with a detailed protocol and flow diagram of the procedure.

  8. MMP-3 gene polymorphisms and Osteosarcoma.

    PubMed

    Adiguzel, Mustafa; Horozoglu, Cem; Kilicoglu, Onder; Ozger, Harzem; Acar, Leyla; Ergen, Arzu

    2016-03-01

    Osteosarcoma (OSA) is the most common adolescence cancer among all primary bone tumors next only to multiplemyeloma. It has a substantially worse prognosis and ability to metastasize to lung. MMPs (matrix metalloproteinases) are among the major proteases that take part in regulation of ECM (extracellular matrix). MMPs play an active role in the formation of the osteoid tissue, rich in collagens and other ECM proteoglycans. They also take part in pro-osteoclast, osteoclast, osteoblast, and osteoid formation. Many members of the MMP gene family have been linked to human cancers. It has been shown that MMPs particularly play a role in the tumor's acquisition of an invasive and metastatic character. In our study, the E45K and T102T polymorphisms of MMP-3 were studied using the PCR-RFLP method in 135 Turkish subjects (54 subjects with osteosarcoma and 81 healthy controls). We found that frequencies of E45K G allele (p:0,010, χ²:6,710, OR:1,429, 95% Cl: 1,019-1,858) and AG genotype (p:0,001, χ²:14,753, OR:2,32, 95% Cl: 1,491-3,626) were elevated in patients compared to controls. Besides, there was a significant difference in.E45K AA genotype between study groups (p:0,004, χ²:8,182, OR: 2,929, 95% Cl: 1,38-6,19). There were no significant differences between any genotypes or allele in the control and patient groups for MMP-3 T102T polymorphism. Our findings indicate that the G allele and AG genotype of MMP-3 E45K polymorphism is associated with increased risk of osteosarcoma in adolescent population of Turkey. PMID:27145630

  9. [Polymorphic loci and polymorphism analysis of short tandem repeats within XNP gene].

    PubMed

    Liu, Qi-Ji; Gong, Yao-Qin; Guo, Chen-Hong; Chen, Bing-Xi; Li, Jiang-Xia; Guo, Yi-Shou

    2002-01-01

    To select polymorphic short tandem repeat markers within X-linked nuclear protein (XNP) gene, genomic clones which contain XNP gene were recognized by homologous analysis with XNP cDNA. By comparing the cDNA with genomic DNA, non-exonic sequences were identified, and short tandem repeats were selected from non-exonic sequences by using BCM search Launcher. Polymorphisms of the short tandem repeats in Chinese population were evaluated by PCR amplification and PAGE. Five short tandem repeats were identified from XNP gene, two of which were polymorphic. Four and 11 alleles were observed in Chinese population for XNPSTR1 and XNPSTR4, respectively. Heterozygosities were 47% for XNPSTR1 and 70% for XNPSTR4. XNPSTR1 and XNPSTR4 localized within 3' end and intron 10, respectively. Two polymorphic short tandem repeats have been identified within XNP gene and will be useful for linkage analysis and gene diagnosis of XNP gene. PMID:12182071

  10. Gene Polymorphisms and Pharmacogenetics in Rheumatoid Arthritis

    PubMed Central

    Rego-Pérez, Ignacio; Fernández-Moreno, Mercedes; Blanco, Francisco J

    2008-01-01

    Rheumatoid arthritis (RA) is a systemic, chronic and inflammatory disease of unknown etiology with genetic predisposition. The advent of new biological agents, as well as the more traditional disease-modifying antirheumatic drugs, has resulted in highly efficient therapies for reducing the symptoms and signs of RA; however, not all patients show the same level of response in disease progression to these therapies. These variations suggest that RA patients may have different genetic regulatory mechanisms. The extensive polymorphisms revealed in non-coding gene-regulatory regions in the immune system, as well as genetic variations in drug-metabolizing enzymes, suggest that this type of variation is of functional and evolutionary importance and may provide clues for developing new therapeutic strategies. Pharmacogenetics is a rapidly advancing area of research that holds the promise that therapies will soon be tailored to an individual patient’s genetic profile. PMID:19506728

  11. Impact of Food Restriction on the Expression of the Adiponectin System and Genes in the Hypothalamic-Pituitary-Ovarian Axis of Pre-Pubertal Ewes.

    PubMed

    Wang, R; Kuang, M; Nie, H; Bai, W; Sun, L; Wang, F; Mao, D; Wang, Z

    2016-10-01

    Adiponectin, a cytokine secreted typically by adipocytes, has been implicated as a molecular switch between female reproduction and energy balance. The present study was undertaken to investigate the expression of adiponectin system and patterns of genes in the hypothalamic-pituitary-ovary (HPO) axis of food-restricted pre-pubertal ewes. Eighteen 2-month-old female ewes were assigned to 3 groups after a pre-feeding ad libitum for 10 days (six in each group): the control group (C), the low-food-restricted group (LR) and the high-food-restricted group (HR), which were fed with 100%, 70% and 50% of ad libitum food intake, respectively. The hypothalamus, pituitary, ovary and serum were collected after food restriction for 2 months. Results by ELISA showed that food restriction increased serum adiponectin concentrations. Quantitative real-time PCR showed that the gene transcriptions for adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2) were enhanced in the hypothalamic-pituitary-ovarian (HPO) axis, while KISS-1/GPR-54 and gonadotropin-releasing hormone (GnRH) in the hypothalamus and luteinizing hormone β-subunit (LHβ) and follicle-stimulating hormone β-subunit (FSHβ) in the pituitary were reduced after food restriction. Immunohistochemistry results demonstrated that AdipoR1 localized in the oocytes of follicles in the ovary. These results suggest that the alterations in the expression of adiponectin and its receptors in response to food restriction might negatively influence the HPO axis. PMID:27405252

  12. The effects of paternal high-fat diet exposure on offspring metabolism with epigenetic changes in the mouse adiponectin and leptin gene promoters.

    PubMed

    Masuyama, Hisashi; Mitsui, Takashi; Eguchi, Takeshi; Tamada, Shoko; Hiramatsu, Yuji

    2016-07-01

    Recent studies have demonstrated that epigenetic changes resulting from malnutrition might play important roles in transgenerational links with metabolic diseases. Previously, we observed that exposure to a high-fat diet (HFD) in utero caused a metabolic syndrome-like phenomenon through epigenetic modifications of the adiponectin and leptin genes that persisted for multiple generations. Recent etiological studies indicated that paternal BMI had effects on offspring BMI that were independent of but additive to maternal BMI effects. Thus, we examined whether paternal HFD-induced obesity affected the metabolic status of offspring through epigenetic changes in the adiponectin and leptin genes. Additionally, we investigated whether a normal diet during subsequent generations abolished the epigenetic changes associated with paternal HFD exposure before conception. We observed the effects of paternal HFD exposure before conception over multiple generations on offspring metabolic traits, including weight and fat gain, glucose intolerance, hypertriglyceridemia, abnormal adipocytokine levels, hypertension, and adiponectin and leptin gene expression and epigenetic changes. Normal diet consumption by male offspring during the subsequent generation following paternal HFD exposure diminished whereas consumption for two generations completely abolished the effect of paternal HFD exposure on metabolic traits and adipocytokine promoter epigenetic changes in the offspring. The effects of paternal HFD exposure on offspring were relatively weaker than those following HFD exposure in utero. However, paternal HFD exposure had an additive metabolic effect for two generations, suggesting that both paternal and maternal nutrition might affect offspring metabolism through epigenetic modifications of adipocytokine genes for multiple generations. PMID:27245335

  13. A gene feature enumeration approach for describing HLA allele polymorphism.

    PubMed

    Mack, Steven J

    2015-12-01

    HLA genotyping via next generation sequencing (NGS) poses challenges for the use of HLA allele names to analyze and discuss sequence polymorphism. NGS will identify many new synonymous and non-coding HLA sequence variants. Allele names identify the types of nucleotide polymorphism that define an allele (non-synonymous, synonymous and non-coding changes), but do not describe how polymorphism is distributed among the individual features (the flanking untranslated regions, exons and introns) of a gene. Further, HLA alleles cannot be named in the absence of antigen-recognition domain (ARD) encoding exons. Here, a system for describing HLA polymorphism in terms of HLA gene features (GFs) is proposed. This system enumerates the unique nucleotide sequences for each GF in an HLA gene, and records these in a GF enumeration notation that allows both more granular dissection of allele-level HLA polymorphism and the discussion and analysis of GFs in the absence of ARD-encoding exon sequences. PMID:26416087

  14. Polymorphisms of the chicken antiviral MX gene.

    PubMed

    Watanabe, T

    2007-01-01

    The Mx gene was originally found in laboratory mice in an infection experiment using influenza virus (Lindermann, 1962). Almost all of the mouse strains in that experiment died from the infection, and only the A2G strain had resistance to the virus. This resistant character was shown to be inherited as a single autosomal dominant trait (Lindermann et al., 1963; Lindermann, 1964; Haller et al., 1979). A congenic mouse strain was established by introducing the Mx+ allele of the A2G resistant strain into the Mx- sensitive inbred strain BALB/c (Staeheli et al., 1984). By immunizing parental BALB/c mice with extracts of interferon (IFN)-treated cultured cells from congenic BALB/c-Mx+ mice, a specific antibody against Mx protein was obtained (Horisberger et al., 1983; Staeheli et al., 1985). The Mx protein was detected in the nucleus of IFN-alpha/beta-treated mouse cells by immunofluorescence using the anti-Mx antibody (Dreiding et al., 1985). Thereafter, by using the antibody as an indicator, cDNA encoding the Mx protein was cloned from a cDNA library constructed from IFN-treated cells of congenic BALB/c-Mx+ mice (Staeheli et al., 1986a). IFN-treated Mx+ mouse cells contained a 3.5-kb Mx mRNA in the Northern blot, while Mx- cells failed to express the transcript. The functional Mx+ gene from an A2G mouse was found to contain 14 exons and encode 631 amino acids. The Mx- allelic mouse strains were found to be missing sequence of exons 9 through 11 or to contain a point mutation that converts lysine at position 389 to a stop codon (Staeheli et al., 1988). If these polymorphisms of the Mx gene could be detected in domestic animals, it would be possible to produce breeds that show resistance to infectious diseases. PMID:17675880

  15. Association between Tryptophan Hydroxylase 2 Gene Polymorphism and Completed Suicide

    ERIC Educational Resources Information Center

    Fudalej, Sylwia; Ilgen, Mark; Fudalej, Marcin; Kostrzewa, Grazyna; Barry, Kristen; Wojnar, Marcin; Krajewski, Pawel; Blow, Frederic; Ploski, Rafal

    2010-01-01

    The association between suicide and a single nucleotide polymorphism (rs1386483) was examined in the recently identified tryptophan hydroxylase 2 (TPH2) gene. Blood samples of 143 suicide victims and 162 age- and sex-matched controls were examined. The frequency of the TT genotype in the TPH2 polymorphism was higher in suicide victims than in…

  16. Polymorphisms in Autophagy Genes and Susceptibility to Tuberculosis

    PubMed Central

    Alisjahbana, Bachti; Sahiratmadja, Edhyana; Parwati, Ida; Oosting, Marije; Plantinga, Theo S.; Joosten, Leo A. B.; Netea, Mihai G.; Ottenhoff, Tom H. M.; van de Vosse, Esther; van Crevel, Reinout

    2012-01-01

    Recent data suggest that autophagy is important for intracellular killing of Mycobacterium tuberculosis, and polymorphisms in the autophagy gene IRGM have been linked with susceptibility to tuberculosis (TB) among African-Americans, and with TB caused by particular M. tuberculosis genotypes in Ghana. We compared 22 polymorphisms of 14 autophagy genes between 1022 Indonesian TB patients and 952 matched controls, and between patients infected with different M. tuberculosis genotypes, as determined by spoligotyping. The same autophagy polymorphisms were studied in correlation with ex-vivo production of TNF, IL-1β, IL-6, IL-8, IFN-γ and IL-17 in healthy volunteers. No association was found between TB and polymorphisms in the genes ATG10, ATG16L2, ATG2B, ATG5, ATG9B, IRGM, LAMP1, LAMP3, P2RX7, WIPI1, MTOR and ATG4C. Associations were found between polymorphisms in LAMP1 (p = 0.02) and MTOR (p = 0.02) and infection with the successful M. tuberculosis Beijing genotype. The polymorphisms examined were not associated with M. tuberculosis induced cytokines, except for a polymorphism in ATG10, which was linked with IL-8 production (p = 0.04). All associations found lost statistical significance after correction for multiple testing. This first examination of a broad set of polymorphisms in autophagy genes fails to show a clear association with TB, with M. tuberculosis Beijing genotype infection or with ex-vivo pro-inflammatory cytokine production. PMID:22879892

  17. Polymorphisms and genes associated with puberty in heifers.

    PubMed

    Fortes, Marina R S; Nguyen, Loan To; Porto Neto, Laercio R; Reverter, Antonio; Moore, Stephen S; Lehnert, Sigrid A; Thomas, Milton G

    2016-07-01

    Puberty onset is a multifactorial process influenced by genetic determinants and environmental conditions, especially nutritional status. Genes, genetic variations, and regulatory networks compose the molecular basis of achieving puberty. In this article, we reviewed the discovery of multiple polymorphisms and genes associated with heifer puberty phenotypes and discuss the opportunities to use this evolving knowledge of genetic determinants for breeding early pubertal Bos indicus-influenced cattle. The discovery of polymorphisms and genes was mainly achieved through candidate gene studies, quantitative trait loci analyses, genome-wide association studies, and recently, global gene expression studies (transcriptome). These studies are recapitulated and summarized in the current review. PMID:27238439

  18. Genetic variants in IGF-I, IGF-II, IGFBP-3, and adiponectin genes and colon cancer risk in African Americans and Whites

    PubMed Central

    Keku, Temitope O.; Vidal, Adriana; Oliver, Shannon; Hoyo, Catherine; Hall, Ingrid J.; Omofoye, Seun; McDoom, Maya; Worley, Kendra; Galanko, Joseph; Sandler, Robert S.; Millikan, Robert

    2014-01-01

    Purpose Evaluating genetic susceptibility may clarify effects of known environmental factors and also identify individuals at high risk. We evaluated the association of four insulin-related pathway gene polymorphisms in insulin-like growth factor-1 (IGF-I) (CA)n repeat, insulin-like growth factor-2 (IGF-II) (rs680), insulin-like growth factor binding protein-3 (IGFBP-3) (rs2854744), and adiponectin (APM1 rs1501299) with colon cancer risk, as well as relationships with circulating IGF-I, IGF-II, IGFBP-3, and C-peptide in a population-based study. Methods Participants were African Americans (231cases, 306 controls) and Whites (297 cases, 530 controls). Consenting subjects provided blood specimens, and lifestyle/diet information. Genotyping for all genes except IGF-I was performed by the 5′-exonuclease (Taqman) assay. The IGF-I (CA)n repeat was assayed by PCR, and fragment analysis. Circulating proteins were measured by enzyme immunoassays. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. Results The IGF-I (CA)19 repeat was higher in White controls (50%) than African American controls (31%). Whites homozygous for the IGF-I (CA)19 repeat had a nearly two fold increase in risk of colon cancer (OR=1.77; 95%CI=1.15–2.73), but not African Americans (OR= 0.73, 95%CI 0.50–1.51). We observed an inverse association between the IGF-II Apa1 A-variant and colon cancer risk (OR= 0.49, 95%CI 0.28–0.88) in Whites only. Carrying the IGFBP-3 variant alleles was associated with lower IGFBP-3 protein levels, a difference most pronounced in Whites (p- trend < 0.05). Conclusions These results support an association between insulin pathway-related genes and elevated colon cancer risk in Whites but not in African Americans. PMID:22565227

  19. A comprehensive analysis of adiponectin QTLs using SNP association, SNP cis-effects on peripheral blood gene expression and gene expression correlation identified novel metabolic syndrome (MetS) genes with potential role in carcinogenesis and systemic inflammation

    PubMed Central

    2013-01-01

    Background Metabolic syndrome (MetS) is an aberration associated with increased risk for cancer and inflammation. Adiponectin, an adipocyte-produced abundant protein hormone, has countering effect on the diabetogenic and atherogenic components of MetS. Plasma levels of adiponectin are negatively correlated with onset of cancer and cancer patient mortality. We previously performed microsatellite linkage analyses using adiponectin as a surrogate marker and revealed two QTLs on chr5 (5p14) and chr14 (14q13). Methods Using individuals from 85 extended families that contributed to the linkage and who were measured for 42 clinical and biologic MetS phenotypes, we tested QTL-based SNP associations, peripheral white blood cell (PWBC) gene expression, and the effects of cis-acting SNPs on gene expression to discover genomic elements that could affect the pathophysiology and complications of MetS. Results Adiponectin levels were found to be highly intercorrelated phenotypically with the majority of MetS traits. QTL-specific haplotype-tagging SNPs associated with MetS phenotypes were annotated to 14 genes whose function could influence MetS biology as well as oncogenesis or inflammation. These were mechanistically categorized into four groups: cell-cell adhesion and mobility, signal transduction, transcription and protein sorting. Four genes were highly prioritized: cadherin 18 (CDH18), myosin X (MYO10), anchor protein 6 of AMPK (AKAP6), and neuronal PAS domain protein 3 (NPAS3). PWBC expression was detectable only for the following genes with multi-organ or with multi-function properties: NPAS3, MARCH6, MYO10 and FBXL7. Strong evidence of cis-effects on the expression of MYO10 in PWBC was found with SNPs clustered near the gene’s transcription start site. MYO10 expression in PWBC was marginally correlated with body composition (p= 0.065) and adipokine levels in the periphery (p = 0.064). Variants of genes AKAP6, NPAS3, MARCH6 and FBXL7 have been previously reported to be

  20. Hepatitis-related hepatocellular carcinoma: Insights into cytokine gene polymorphisms.

    PubMed

    Dondeti, Mahmoud Fathy; El-Maadawy, Eman Anwar; Talaat, Roba Mohamed

    2016-08-14

    Hepatocellular carcinoma (HCC) is a primary liver cancer, which is one of the most prevalent cancers among humans. Many factors are involved in the liver carcinogenesis as lifestyle and environmental factors. Hepatitis virus infections are now recognized as the chief etiology of HCC; however, the precise mechanism is still enigmatic till now. The inflammation triggered by the cytokine-mediated immune response, was reported to be the closest factor of HCC development. Cytokines are immunoregulatory proteins produced by immune cells, functioning as orchestrators of the immune response. Genes of cytokines and their receptors are known to be polymorphic, which give rise to variations in their genes. These variations have a great impact on the expression levels of the secreted cytokines. Therefore, cytokine gene polymorphisms are involved in the molecular mechanisms of several diseases. This piece of work aims to shed much light on the role of cytokine gene polymorphisms as genetic host factor in hepatitis related HCC. PMID:27570418

  1. Hepatitis-related hepatocellular carcinoma: Insights into cytokine gene polymorphisms

    PubMed Central

    Dondeti, Mahmoud Fathy; El-Maadawy, Eman Anwar; Talaat, Roba Mohamed

    2016-01-01

    Hepatocellular carcinoma (HCC) is a primary liver cancer, which is one of the most prevalent cancers among humans. Many factors are involved in the liver carcinogenesis as lifestyle and environmental factors. Hepatitis virus infections are now recognized as the chief etiology of HCC; however, the precise mechanism is still enigmatic till now. The inflammation triggered by the cytokine-mediated immune response, was reported to be the closest factor of HCC development. Cytokines are immunoregulatory proteins produced by immune cells, functioning as orchestrators of the immune response. Genes of cytokines and their receptors are known to be polymorphic, which give rise to variations in their genes. These variations have a great impact on the expression levels of the secreted cytokines. Therefore, cytokine gene polymorphisms are involved in the molecular mechanisms of several diseases. This piece of work aims to shed much light on the role of cytokine gene polymorphisms as genetic host factor in hepatitis related HCC. PMID:27570418

  2. Melanoma risk is associated with vitamin D receptor gene polymorphisms.

    PubMed

    Zeljic, Katarina; Kandolf-Sekulovic, Lidija; Supic, Gordana; Pejovic, Janko; Novakovic, Marijan; Mijuskovic, Zeljko; Magic, Zvonko

    2014-06-01

    Previous studies have reported that vitamin D receptor (VDR) gene polymorphisms are associated with the occurrence of various cancers, including melanoma. The aim of the current study was to investigate the association of VDR gene polymorphisms with melanoma risk, clinicopathological characteristics, and vitamin D levels. The study group included 117 patients (84 patients with superficial spreading melanoma and 33 patients with nodular melanoma). The control group included 122 sex-matched and age-matched healthy-blood donors of the same ethnicity. VDR gene polymorphisms FokI, EcoRV, TaqI, and ApaI were genotyped by real-time PCR. In 60 patients, the total 25-hydroxyvitamin D levels were evaluated in serum samples by direct chemiluminescence. Associations among parameters were considered to be significant if the P value was less than 0.05. Significant differences in the frequencies of VDR genotypes were observed between cases and the control group for FokI and TaqI polymorphisms (P<0.0001; P=0.005, respectively). Heterozygous Ff as well as mutant FF genotypes of the FokI polymorphism were associated with increased melanoma risk compared with the wild-type form [odds ratio (OR)=3.035, P=0.003; OR=9.276, P<0.0001, respectively]. A significantly increased melanoma risk was observed for the heterozygous Tt (OR=2.302, P=0.011) and the mutated variant tt (OR=3.697, P=0.003) of the TaqI polymorphism in comparison with the wild-type genotype. None of the polymorphisms studied was associated with clinicopathological characteristics and vitamin D serum level. Our results suggest that FokI and TaqI polymorphisms in the VDR gene may be considered as potential biomarkers for melanoma susceptibility. Low vitamin D levels in melanoma patients indicate the need for vitamin D supplementation. PMID:24638155

  3. [BCL1 POLYMORPHISM OF GLUCOCORTICOID RECEPTOR GENE AND RESPIRATORY DISEASES].

    PubMed

    Prystupa, L N; Garbuzova, V Yu; Kmyta, V V

    2015-01-01

    The article analyses the results of investigating the connection between BCL1-polymorphism of glucocorticoid receptor gene and respiratory diseases. Its role in increasing sensitivity to glucocorticoids is proved here. The authors investigated the association of Bcl1 polymorphism with predisposition to bronchial asthma, chronic obstructive pulmonary disease, with the nicotine addiction degree and with progressing disorders of pulmonary function in cystic fibrosis. PMID:26118026

  4. The effect of adiponectin on osteonectin gene expression by oxidized low density lipoprotein-treated vascular smooth muscle cells.

    PubMed

    Niknam, Sara; Ghatreh-Samani, Keihan; Farrokhi, Effat

    2015-01-01

    Osteonectin is a bone- associated protein involved in vascular calcification. Adiponectin may protect against cardiovascular disease but possible effects on vascular calcification have been poorly studied. The aim of this study was to investigate the modulatory effect of adiponectin on oxidized low density lipoprotein (oxLDL)- induced expression of osteonectin in human aorta vascular smooth muscle cells (HA/VSMCs). HA/VSMCs were cultured in F12K media and then treated with oxLDL (100 µg/mL) in the presence or absence of adoponectin (5 µg/mL) for 24 and 48 hours. mRNA expression and protein level of osteonectin were determined by quantitative real-time PCR and western blot analysis, respectively. After exposure to oxLDL, osteonectin expression increased 1.62 ± 0.23- and 6.62 ± 0.48-fold after 24 and 48 hours respectively compared to the control. Adiponectin increased oxLDL- induced osteonectin expression in a time-dependent manner after 24 and 48 hours (3.24 ± 0.39- and 24.93 ± 2.15-fold, respectively). Western blotting confirmed that osteonectin protein was upregulated by adiponectin.Our data suggest that OxLDL might cause the increase of osteonectin expression both at mRNA and protein level. This upregulation is intensified by adiponectin. PMID:25815284

  5. The Effect of Adiponectin on Osteonectin Gene Expression by Oxidized Low Density Lipoprotein-Treated Vascular Smooth Muscle Cells

    PubMed Central

    Niknam, Sara; Ghatreh-Samani, Keihan; Farrokhi, Effat

    2015-01-01

    Osteonectin is a bone- associated protein involved in vascular calcification. Adiponectin may protect against cardiovascular disease but possible effects on vascular calcification have been poorly studied. The aim of this study was to investigate the modulatory effect of adiponectin on oxidized low density lipoprotein (oxLDL)- induced expression of osteonectin in human aorta vascular smooth muscle cells (HA/VSMCs). HA/VSMCs were cultured in F12K media and then treated with oxLDL (100 µg/mL) in the presence or absence of adoponectin (5 µg/mL) for 24 and 48 hours. mRNA expression and protein level of osteonectin were determined by quantitative real-time PCR and western blot analysis, respectively. After exposure to oxLDL, osteonectin expression increased 1.62 ± 0.23- and 6.62 ± 0.48-fold after 24 and 48 hours respectively compared to the control. Adiponectin increased oxLDL- induced osteonectin expression in a time-dependent manner after 24 and 48 hours (3.24 ± 0.39- and 24.93 ± 2.15-fold, respectively). Western blotting confirmed that osteonectin protein was upregulated by adiponectin.Our data suggest that OxLDL might cause the increase of osteonectin expression both at mRNA and protein level. This upregulation is intensified by adiponectin. PMID:25815284

  6. Central adiponectin acutely improves glucose tolerance in male mice.

    PubMed

    Koch, Christiane E; Lowe, Chrishanthi; Legler, Karen; Benzler, Jonas; Boucsein, Alisa; Böttiger, Gregor; Grattan, David R; Williams, Lynda M; Tups, Alexander

    2014-05-01

    Adiponectin, an adipocyte-derived hormone, regulates glucose and lipid metabolism. It is also antiinflammatory. During obesity, adiponectin levels and sensitivity are reduced. Whereas the action of adiponectin in the periphery is well established the neuroendocrine role of adiponectin is largely unknown. To address this we analyzed the expression of adiponectin and the 2 adiponectin receptors (AdipoR1 and AdipoR2) in response to fasting and to diet-induced and genetic obesity. We also investigated the acute impact of adiponectin on central regulation of glucose homeostasis. Adiponectin (1 μg) was injected intracerebroventricularly (ICV), and glucose tolerance tests were performed in dietary and genetic obese mice. Finally, the influence of ICV adiponectin administration on central signaling cascades regulating glucose homeostasis and on markers of hypothalamic inflammation was assessed. Gene expression of adiponectin was down-regulated whereas AdipoR1 was up-regulated in the arcuate nucleus of fasted mice. High-fat (HF) feeding increased AdipoR1 and AdipoR2 gene expression in this region. In mice on a HF diet and in leptin-deficient mice acute ICV adiponectin improved glucose tolerance 60 minutes after injection, whereas normoglycemia in control mice was unaffected. ICV adiponectin increased pAKT, decreased phospho-AMP-activated protein kinase, and did not change phospho-signal transducer and activator of transcription 3 immunoreactivity. In HF-fed mice, ICV adiponectin reversed parameters of hypothalamic inflammation and insulin resistance as determined by the number of phospho-glycogen synthase kinase 3 β(Ser9) and phospho-c-Jun N-terminal kinase (Thr183/Tyr185) immunoreactive cells in the arcuate nucleus and ventromedial hypothalamus. This study demonstrates that the insulin-sensitizing properties of adiponectin are at least partially based on a neuroendocrine mechanism that involves centrally synthesized adiponectin. PMID:24564394

  7. Adiponectin in childhood.

    PubMed

    Jeffery, Alison N; Murphy, Michael J; Metcalf, Brad S; Hosking, Joanne; Voss, Linda D; English, Patrick; Sattar, Naveed; Wilkin, Terence J

    2008-01-01

    Adiponectin, a hormone produced and secreted by adipocytes, is present in circulation in high circulating concentrations, suggesting an important physiological role. An indirect regulator of glucose metabolism, adiponectin increases insulin sensitivity, improves glucose tolerance and inhibits inflammation. Plasma adiponectin relates inversely to adiposity and, importantly, reflects the sequelae of accumulation of excess adiposity. The role of adiponectin in adults has been explored in detail. Studies in children are now available and, given the increasing rates of childhood obesity, it is important to establish the role of adiponectin in mediating insulin resistance and cardiovascular disease in this age group. This paper reviews the regulation of adiponectin, its effect on body mass, glucose metabolism and cardiovascular risk in infants, children and adolescents. It demonstrates clear links between adiponectin and features of the metabolic syndrome in obese children and adolescents. However, adiponectin's role as a predictor of metabolic dysfunction in healthy, normal-weight youngsters is less clear. PMID:19086185

  8. Gene-gene interaction of erythropoietin gene polymorphisms and diabetic retinopathy in Chinese Han.

    PubMed

    Fan, YanFei; Fu, Yin-Yu; Chen, Zhi; Hu, Yuan-Yuan; Shen, Jie

    2016-08-01

    The aim of this study was to investigate the association of three single nucleotide polymorphisms in the erythropoietin gene polymorphisms with diabetic retinopathy and additional role of gene-gene interaction on diabetic retinopathy risk. A total of 1193 patients (579 men, 614 women) with type 2 diabetes mellitus were selected, including 397 diabetic retinopathy patients and 796 controls (type 2 diabetes mellitus patients without diabetic retinopathy); the mean age of all participants was 56.7 ± 13.9 years. Three single nucleotide polymorphisms were selected: rs507392, rs1617640, and rs551238. The t-test was used for comparison of erythropoietin protein level erythropoietin levels in patients having different erythropoietin genotypes. Logistic regression model was used to examine the association between three single nucleotide polymorphisms and diabetic retinopathy. Odds ratio (OR) and 95% confident interval (95% CI) were calculated. Generalized multifactor dimensionality reduction was employed to analyze the impact of interaction among three single nucleotide polymorphisms on CVD risk. After covariates adjustment, the carriers of homozygous mutant of three single nucleotide polymorphisms have higher diabetic retinopathy risk than those with wild-type homozygotes, OR (95% CI) were 2.04 (1.12-2.35), 1.87 (1.10-2.41) and 1.15 (1.06-1.76), respectively. Generalized multifactor dimensionality reduction model indicated a significant three-locus model (p = 0.0010) involving rs507392, rs1617640, and rs551238. Overall, the three-locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 60.72%. Subjects with TC or CC-TG or GG-AC or CC genotype have the highest diabetic retinopathy risk. In conclusion, our results support an important association of rs507392, rs1617640 and rs551238 minor allele of erythropoietin with increased diabetic retinopathy risk, and additional interaction among three single nucleotide polymorphisms. PMID

  9. Effect of adiponectin on the steroidogenic acute regulatory protein, P450 side chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase gene expression, progesterone and androstenedione production by the porcine uterus during early pregnancy.

    PubMed

    Smolinska, N; Dobrzyn, K; Kiezun, M; Szeszko, K; Maleszka, A; Kaminski, T

    2016-06-01

    Adiponectin and its receptors are expressed in the human and porcine uterus and this endocrine system has important role in the regulation of reproductive processes. The expression of steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (HSD3B1) were observed in the human and porcine uterus during the oestrous cycle and pregnancy. The de novo synthesis of steroids in the uterus might be a crucial factor for effective implantation and maintenance of pregnancy. We hypothesized that adiponectin modulates the expression of key enzymes in the synthesis of the steroids: StAR, P450 side chain cleavage enzyme (CYP11A1) and HSD3B1, as well as progesterone (P4) and androstenedione (A4) secretion by the porcine uterus. Endometrial and myometrial explants harvested from gilts (n = 5) on days 10 to 11, 12 to 13, 15 to 16 and 27 to 28 of pregnancy and on days 10 to 11 of the oestrous cycle were cultured in vitro in the presence of adiponectin (1, 10 μg/ml), adiponectin with insulin (10 ng/ml) and insulin alone (10 ng/ml). Gene expression was examined by real-time PCR, and the secretion of the steroids was determined by radioimmunoassay. The content of StAR, CYP11A1 and HSD3B1 mRNAs and the secretion of P4 and A4 was modulated by adiponectin in endometrial and myometrial tissue explants during early pregnancy and the oestrous cycle. In this action adiponectin interacted with insulin. Insulin itself also regulated the steroidogenic activity of the porcine uterus. ere we reported, for the first time, the expression of CYP11A1 genes in the porcine endometrium and myometrium. Our novel findings indicate that adiponectin affects basal and insulin-stimulated expression of key steroidogenic genes and production of steroid hormones by the porcine uterus during maternal recognition of pregnancy and implantation. PMID:27512005

  10. Association Between IL-10 Gene Polymorphism and Diabetic Retinopathy

    PubMed Central

    Dong, Hongtao; Li, Qiuming; Wang, Menghua; Wan, Guangming

    2015-01-01

    Background Genetic and environmental factors both play important roles in the occurrence and progression of diabetic retinopathy (DR). IL-10 592 gene polymorphism is associated with diabetes pathogenesis. This study analyzed the relationship between IL-10 gene promoter-592 loci polymorphism (SNP) in a diabetic model rats with DR. Material/Methods Streptozotocin (STZ) was injected through the tail vein to establish a diabetic rat model. The rats were randomly divided into 2 groups for 3 months’ feeding, including 100 rats in the diabetes-positive control group and 100 rats only injected with citric acid buffer as the blank control group. Fundus fluorescein angiography (FFA) was used to observe retinal vascular changes. Polymerase chain reaction-restriction fragment polymorphisms assay (PCR-RFLP) was used to detect IL-10 gene promoter-592 loci polymorphism in DNA samples. Enzyme-linked immunosorbent assay (ELISA) was performed to test serum IL-10 concentration. Results Serum IL-10 level in DR rats was 33.18±5.0 pg/mL and in the control rats it was 53.33±4.16 pg/mL in (P<0.01). Diabetes susceptibility with IL-10-592 genotype frequency and gene frequency analysis showed that IL-10-592 genotype frequency and allele frequency were significantly different in the DR group compared with the control group (P<0.01). Conclusions IL-10 592 polymorphism was associated with DR susceptibility, suggesting that the gene polymorphism might be a risk factor for DR. PMID:26492380

  11. Polymorphism of the DNA Base Excision Repair Genes in Keratoconus

    PubMed Central

    Wojcik, Katarzyna A.; Synowiec, Ewelina; Sobierajczyk, Katarzyna; Izdebska, Justyna; Blasiak, Janusz; Szaflik, Jerzy; Szaflik, Jacek P.

    2014-01-01

    Keratoconus (KC) is a degenerative corneal disorder for which the exact pathogenesis is not yet known. Oxidative stress is reported to be associated with this disease. The stress may damage corneal biomolecules, including DNA, and such damage is primarily removed by base excision repair (BER). Variation in genes encoding BER components may influence the effectiveness of corneal cells to cope with oxidative stress. In the present work we genotyped 5 polymorphisms of 4 BER genes in 284 patients and 353 controls. The A/A genotype of the c.–1370T>A polymorphism of the DNA polymerase γ (POLG) gene was associated with increased occurrence of KC, while the A/T genotype was associated with decreased occurrence of KC. The A/G genotype and the A allele of the c.1196A>G polymorphism of the X-ray repair cross-complementing group 1 (XRCC1) were associated with increased, and the G/G genotype and the G allele, with decreased KC occurrence. Also, the C/T and T as well as C/C genotypes and alleles of the c.580C>T polymorphism of the same gene displayed relationship with KC occurrence. Neither the g.46438521G>C polymorphism of the Nei endonuclease VIII-like 1 (NEIL1) nor the c.2285T>C polymorphism of the poly(ADP-ribose) polymerase-1 (PARP-1) was associated with KC. In conclusion, the variability of the XRCC1 and POLG genes may play a role in KC pathogenesis and determine the risk of this disease. PMID:25356504

  12. Relationship of MTHFR gene polymorphisms with renal and cardiac disease

    PubMed Central

    Trovato, Francesca M; Catalano, Daniela; Ragusa, Angela; Martines, G Fabio; Pirri, Clara; Buccheri, Maria Antonietta; Di Nora, Concetta; Trovato, Guglielmo M

    2015-01-01

    AIM: To investigate the effects of different methylenetetrahydrofolate reductase (MTHFR) 677C>T gene polymorphism and hyperhomocysteinemia for the development of renal failure and cardiovascular events, which are controversial. METHODS: We challenged the relationship, if any, of MTHFR 677C>T and MTHFR 1298A>C polymorphisms with renal and heart function. The present article is a reappraisal of these concepts, investigating within a larger population, and including a subgroup of dialysis patients, if the two most common MTHFR polymorphisms, C677T and A1298C, as homozygous, heterozygous or with a compound heterozygous state, show different association with chronic renal failure requiring hemodialysis. MTHFR polymorphism could be a favorable evolutionary factor, i.e., a protective factor for many ominous conditions, like cancer and renal failure. A similar finding was reported in fatty liver disease in which it is suggested that MTHFR polymorphisms could have maintained and maintain their persistence by an heterozygosis advantage mechanism. We studied a total of 630 Italian Caucasian subject aged 54.60 ± 16.35 years, addressing to the increased hazard of hemodialysis, if any, according to the studied MTHFR genetic polymorphisms. RESULTS: A favorable association with normal renal function of MTHFR polymorphisms, and notably of MTHFR C677T is present independently of the negative effects of left ventricular hypertrophy, increased Intra-Renal arterial Resistance and hyperparathyroidism. CONCLUSION: MTHFR gene polymorphisms could have a protective role on renal function as suggested by their lower frequency among our dialysis patients in end-stage renal failure; differently, the association with left ventricular hypertrophy and reduced left ventricular relaxation suggest some type of indirect, or concurrent mechanism. PMID:25664255

  13. Relationship between TBX20 gene polymorphism and congenital heart disease.

    PubMed

    Yang, X F; Zhang, Y F; Zhao, C F; Liu, M M; Si, J P; Fang, Y F; Xing, W W; Wang, F L

    2016-01-01

    Congenital heart disease in children is a type of birth defect. Previous studies have suggested that the transcription factor, TBX20, is involved in the occurrence and development of congenital heart disease in children; however, the specific regulatory mechanisms are yet to be evaluated. Hence, this study aimed to evaluate the relationship between the TBX20 polymorphism and the occurrence and development of congenital heart disease. The TBX20 gene sequence was obtained from the NCBI database and the polymorphic locus candidate was predicted. Thereafter, the specific gene primers were designed for the restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) of DNA extracted from the blood of 80 patients with congenital heart disease and 80 controls. The results of the PCR were subjected to correlation analysis to identify the differences between the amplicons and to determine the relationship between the TBX20 gene polymorphism and congenital heart disease. One of the single nucleotide polymorphic locus was found to be rs3999950: c.774T>C (Ala265Ala). The TC genotype frequency in the patients was higher than that in the controls, similar to that for the C locus. The odds ratio of the TC genotypes was above 1, indicating that the presence of the TC genotype increases the incidence of congenital heart diseases. Thus, rs3999950 may be associated with congenital heart disease, and TBX20 may predispose children to the defect. PMID:27323105

  14. Genetic study of eight AKT1 gene polymorphisms and their interaction with DRD2 gene polymorphisms in tardive dyskinesia.

    PubMed

    Zai, Clement C; Romano-Silva, Marco A; Hwang, Rudi; Zai, Gwyneth C; Deluca, Vincenzo; Müller, Daniel J; King, Nicole; Voineskos, Aristotle N; Meltzer, Herbert Y; Lieberman, Jeffrey A; Potkin, Steven G; Remington, Gary; Kennedy, James L

    2008-12-01

    Tardive dyskinesia (TD) is a motor adverse effect of chronic antipsychotic medication. It has been suggested to involve dopamine neurotransmission system changes. AKT1 acts downstream of the D(2) receptor that is blocked by all antipsychotics to some degree. The AKT1 gene has not been investigated in TD. We examined eight polymorphisms spanning the AKT1 gene and their association with TD in our schizophrenia sample of 193 Caucasians, 76 of which with TD. AKT1 polymorphisms and haplotypes were not significantly associated with TD. However, we detected a significant interaction between rs6275 of DRD2 and rs3730358 of AKT1 (p<1 x 10(-5)). PMID:18838251

  15. PEROXIDASE GENE POLYMORPHISM IN BUFFALOGRASS AND OTHER GRASSES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant peroxidases are a family of related proteins possessing highly conserved domains. Degenerate oligonucleotide primers based on these conserved domains can be used to amplify DNA sequences coding for peroxidases from plants with unsequenced genomes. Polymorphisms in peroxidase genes among buffa...

  16. MEL gene polymorphism in the genus Saccharomyces.

    PubMed Central

    Turakainen, H; Aho, S; Korhola, M

    1993-01-01

    In Saccharomyces spp. the ability to use melibiose depends on the presence of a MEL gene encoding alpha-galactosidase. We used two cloned MEL genes as probes to characterize the physical structure and chromosomal location of the MEL genes in several industrial and natural Mel+ strains of Saccharomyces cerevisiae, Saccharomyces pastorianus, and Saccharomyces bayanus. Electrokaryotyping showed that all of the S. pastorianus strains and most of the S. bayanus strains studied had one MEL locus. The MEL gene in S. bayanus strains was similar but not identical to the S. pastorianus MEL gene. Mel+ S. cerevisiae strains had one to seven loci containing MEL sequences. The MEL genes of these strains could be divided into two categories on the basis of hybridization to MEL1, one group exhibiting strong hybridization to MEL1 and the other group exhibiting weak hybridization to MEL1. In S. pastorianus and S. bayanus strains, the MEL gene was expressed as a single 1.5-kb transcript, and the expression was galactose inducible. In some S. cerevisiae strains, the MEL genes were expressed even without induction at fairly high levels. Expression was usually further induced by galactose. In two strains, CBS 5378 and CBS 4903, expression of the MEL genes was at the same level without induction as it was in most other strains with induction. In all S. cerevisiae strains, irrespective of the number of MEL genes, mRNA of only one size (1.6 kb) was observed. Images PMID:8396384

  17. Gene polymorphisms of fibrinolytic enzymes in coal workers' pneumoconiosis

    SciTech Connect

    Chang, L.C.; Tseng, J.C.; Hua, C.C.; Liu, Y.C.; Shieh, W.B.; Wu, H.P.

    2006-03-15

    The authors assessed the gene polymorphisms of missense C/T polymorphism in exon 6 of the urokinase-plasminogen activator (PLAU) gene (PLAU P141L), A/u-repeat in intron 8 of the tissue-type plasminogen activator (PLAT) gene (PLAT TPA25 Alu insertion), and 4G/5G in the promoter region of the serine proteinase inhibitor, clade E (SERPINE) or plasminogen activator inhibitor type 1 gene (SERPINE1 -675 4G/5G) in 153 healthy volunteers and 154 retired coal miners with coal miners' pneumoconiosis (CWP). The CWP subjects included 94 individuals with simple pneumoconiosis and 60 individuals with progressive massive fibrosis presenting with worse pulmonary function. The distributions of genotypes of these three genes did not differ between the control and CWP subjects or between subjects with simple pneumoconiosis and those with progressive massive fibrosis. However, by assessing duration of work and its interaction with genotypes by means of logistic regression, the authors found the missense C/T polymorphism in exon 6 of the PLAU gene to be an effect modifier of the association between work duration and the development of progressive massive fibrosis.

  18. Gene Polymorphism Studies in a Teaching Laboratory

    ERIC Educational Resources Information Center

    Shultz, Jeffry

    2009-01-01

    I present a laboratory procedure for illustrating transcription, post-transcriptional modification, gene conservation, and comparative genetics for use in undergraduate biology education. Students are individually assigned genes in a targeted biochemical pathway, for which they design and test polymerase chain reaction (PCR) primers. In this…

  19. Mutations and a polymorphism in the tuberin gene

    SciTech Connect

    Northup, H.; Rodriguez, J.A.; Au, K.S.; Rodriguez, E.

    1994-09-01

    Two deletions and a polymorphism have been identified in the recently described tuberin gene. The tuberin gene (designated TSC2) when mutated causes tuberous sclerosis complex (TSC). Fifty-three affected individuals (30 from families with multiple affected and 23 isolated cases) were screened with the tuberin cDNA for gross deletions or rearrangements. Both deletions were found in families with multiple affected members (family designations: HOU-5 and HOU-22). The approximate size of the deletion in HOU-5 is ten kilobases and eliminates a BamHI restriction site. The deletion includes a portion of the 5{prime} half of the tuberin cDNA. The deletion in HOU-22 occurs in the 3{prime} half of the gene. The deletions are being further characterized. A HindIII restriction site polymorphism was detected by a 0.5 kilobase probe from the 5{prime} coding region of the tuberin gene in an individual from a family linked to chromosome 9 (posterior probability of linkage 93%). The polymorphism did not segregate with TSC in the family. The family had previously been shown to give negative results with multiple markers on chromosome 16. The polymorphism was also seen in one individual among a panel of 20 randomly selected unaffected individuals. Thirty-five additional affected probands (five from families and 30 isolated cases) are being tested with the tuberin cDNA. Testing for subtle mutations is our panel of 80 affected probands is underway utilizing SSCP. Additional mutations or polymorphisms detected will be reported. The tuberin cDNA was a kind gift of The European Chromosome 16 Tuberous Sclerosis Consortium.

  20. Association between serotonin transporter gene polymorphism and recurrent aphthous stomatitis

    PubMed Central

    Manchanda, Aastha; Iyengar, Asha R.; Patil, Seema

    2016-01-01

    Background: Anxiety-related traits have been attributed to sequence variability in the genes coding for serotonin transmission in  the brain. Two alleles, termed long (L) and short (S) differing by 44 base pairs, are found in a polymorphism identified in the promoter region of serotonin transporter gene. The presence of the short allele  and SS and LS genotypes is found to be associated with the reduced expression of this gene decreasing the uptake of serotonin in the brain leading to various anxiety-related traits. Recurrent aphthous stomatitis (RAS) is an oral mucosal disease with varied etiology including the presence of stress, anxiety, and genetic influences. The present study aimed to determine this serotonin transporter gene polymorphism in patients with RAS and compare it with normal individuals. Materials and Methods: This study included 20 subjects with various forms of RAS and 20 normal healthy age- and gender-matched individuals. Desquamated oral mucosal cells were collected for DNA extraction and subjected to polymerase chain reaction for studying insertion/deletion in the 5-HTT gene-linked polymorphic region. Cross tabulations followed by Chi-square tests were performed to compare the significance of findings, P < 0.05 was considered statistically significant. Results: The LS genotype was the most common genotype found in the subjects with aphthous stomatitis (60%) and controls (40%). The total percentage of LS and SS genotypes and the frequency of S allele were found to be higher in the subjects with aphthous stomatitis as compared to the control group although a statistically significant correlation could not be established, P = 0.144 and 0.371, respectively. Conclusion: Within the limitations of this study, occurrence of RAS was not found to be associated with polymorphic promoter region in serotonin transporter gene. PMID:27274339

  1. Lactotransferrin Gene Polymorphism Associated with Caries Experience.

    PubMed

    Doetzer, Andrea D; Brancher, João A; Pecharki, Giovana D; Schlipf, Nina; Werneck, Renata; Mira, Marcelo T; Riess, Olaf; Bauer, Peter; Trevilatto, Paula Cristina

    2015-01-01

    Dental caries is a common multifactorial disease, resulting from the interaction of biofilm, cariogenic diet and host response over time. Lactotransferrin (LTF) is a main salivary glycoprotein, which modulates the host immune-inflammatory and antibacterial response. Although a genetic component for caries outcome has been identified, little is known over the genetic aspects underlying its susceptibility. Thus, the aim of this study was to investigate the association between LTF polymorphisms and caries susceptibility. Six hundred seventy seven 12-year-old students were selected: 346 with (DMFT ≥ 1) and 331 without caries experience (DMFT = 0). Also, individuals concentrating higher levels of disease (polarization group, DMFT ≥ 2, n = 253) were tested against those with DMFT ≤ 1 (n = 424). Along with clinical parameters, three representative LTF tag SNPs (rs6441989, rs2073495, rs11716497) were genotyped and the results were evaluated using univariate and multivariate analyses. Allele A for tag SNP rs6441989 was found to be significantly less frequent in the polarization group, conferring a protective effect against caries experience [AA + AG × GG (OR: 0.710, 95% CI: 0.514-0.980, p = 0.045)], and remained significantly associated with caries protection in the presence of gingivitis (p = 0.020) and plaque (p = 0.035). These results might contribute to the understanding of the genetic control of caries susceptibility in humans. PMID:25998152

  2. Maternal adiponectin controls milk composition to prevent neonatal inflammation.

    PubMed

    Jin, Zixue; Du, Yang; Schwaid, Adam G; Asterholm, Ingrid W; Scherer, Philipp E; Saghatelian, Alan; Wan, Yihong

    2015-04-01

    Adiponectin is an important adipokine. Increasing evidence suggests that altered adiponectin levels are linked with metabolic and inflammatory disorders. Here we report an important yet previously unrecognized function of adiponectin in lactation by which maternal adiponectin determines the inflammatory status in the nursing neonates. Surprisingly, both maternal adiponectin overexpression in the transgenic mice and maternal adiponectin deletion in the knockout mice lead to systemic inflammation in the pups, manifested as transient hair loss. However, distinct mechanisms are involved. Adiponectin deficiency triggers leukocyte infiltration and production of inflammatory cytokines in the lactating mammary gland. In contrast, adiponectin overabundance increases lipid accumulation in the lactating mammary gland, resulting in excessive long-chain saturated fatty acids in milk. Interestingly, in both cases, the inflammation and alopecia in the pups can be rescued by Toll-like receptor (TLR)-2/4 deletion because TLR2/4 double-knockout pups are resistant. Mechanistically, long-chain saturated fatty acid activation of inflammatory genes is TLR2/4 dependent and can be potentiated by proinflammatory cytokines, indicating that the inflammatory stimuli in both scenarios functionally converge by activating the TLR2/4 signaling. Therefore, our findings reveal adiponectin as a dosage-dependent regulator of lactation homeostasis and milk quality that critically controls inflammation in the nursing neonates. Furthermore, these results suggest that inflammatory infantile disorders may result from maternal adiponectin dysregulation that can be treated by TLR2/4 inhibition. PMID:25590242

  3. Assessment of CASP gene polymorphisms in periodontal disease.

    PubMed

    Kang, S W; Kim, S K; Chung, J H; Ban, J Y

    2015-01-01

    Caspases (CASP) are intracellular proteases that play roles as mediators of apoptosis. Activation of caspase 3 is enhanced in chronic periodontitis. Thus, we hypothesized that single nucleotide polymorphisms (SNPs) of CASP genes might be associated with this condition in the Korean population. To investigate whether such polymorphisms might be involved in the development of periodontal disease, 51 patients and 33 control subjects were assessed. A total of 201 CASP gene SNPs were analyzed with genotypes being determined using and Axiom(TM) genome-wide human assay. SNPStats and SPSS 18.0 were used for the analysis of genetic data and logistic regression models were utilized to evaluate odds ratios, 95% confidence intervals, and P values. Of the 201 SNPs, only three (rs12108497, rs4647602, and rs113420705, all in the CASP3 gene) were significantly associated with chronic periodontitis (P < 0.05). The minor allele frequencies of these SNPs were higher in the patient group than in the control group. In addition, the TC and GT haplotypes formed by rs4647602 and rs113420705 were found to be associated with chronic this disease (TC haplotype, P = 0.0039; GT haplotype, P = 0.002). These results suggest that CASP3 gene polymorphisms may be associated with susceptibility to periodontal disease in the Korean population. PMID:26782454

  4. High proportions of deleterious polymorphisms in constrained human genes.

    PubMed

    Subramanian, Sankar

    2011-01-01

    Previous studies on human mitochondrial genomes showed that the ratio of intra-specific diversities at nonsynonymous-to-synonymous positions was two to ten times higher than the ratio of interspecific divergences at these positions, suggesting an excess of slightly deleterious nonsynonymous polymorphisms. However, such an overabundance of nonsynonymous single nucleotide polymorphisms (SNPs) was not found in human nuclear genomes. Here, genome-wide estimates using >14,000 human-chimp nuclear genes and 1 million SNPs from four human genomes showed a significant proportion of deleterious nonsynonymous SNPs (∼ 15%). Importantly, this study reveals a negative correlation between the magnitude of selection pressure and the proportion of deleterious SNPs on human genes. The proportion of deleterious amino acid replacement polymorphisms is 3.5 times higher in genes under high purifying selection compared with that in less constrained genes (28% vs. 8%). These results are explained by differences in the extent of contribution of mildly deleterious mutations to diversity and substitution. PMID:20974690

  5. The interleukin-1 family gene polymorphisms and Graves' disease.

    PubMed

    Khalilzadeh, O; Anvari, M; Esteghamati, A; Momen-Heravi, F; Mahmoudi, M; Rashidi, A; Amiri, H M; Ranjbar, M; Tabataba-Vakili, S; Amirzargar, A

    2010-09-01

    Genetic factors, including cytokine gene polymorphisms, are potential contributors to the pathogenesis of the Graves' disease (GD). We attempted in this study to determine the association between GD and the following polymorphisms in the interleukin-1 (IL-1) family genes: IL-1alpha (-889C/T), IL-1ss (-511C/T), IL-1ss (+3962C/T), IL-1R (Pst-1 1970C/T) and IL-1RA (Mspa-I 11100C/T). We studied 107 patients with an established diagnosis of GD and 140 healthy controls. Cytokine typing was performed by the polymerase chain reaction with sequence-specific primers assay. Genotype distributions among patients were in Hardy-Weinberg equilibrium for all polymorphisms. The frequency of the IL-1alpha -889T allele was significantly higher in patients than in controls (51.9% vs. 31.6%, OR=2.33, 95% CI=1.61-3.38; p<0.0001). The IL-1RA Msp-I 11100C allele was significantly more frequent in patients than in controls (50.0% vs. 22.9%, OR=3.38, 95% CI=2.29-4.97, p<0.0001). No significant associations were found for other polymorphisms. Although the IL-1 family has well-known roles in GD pathogenesis, the contributions of their genetic variations to the disease are unclear. In this study, we documented a highly significant association between GD and polymorphism in IL-1alpha and IL-1RA genes. Further studies in other populations are necessary to confirm our results. PMID:20400062

  6. Impact of ESR1 Gene Polymorphisms on Migraine Susceptibility

    PubMed Central

    Li, Li; Liu, Ruozhuo; Dong, Zhao; Wang, Xiaolin; Yu, Shengyuan

    2015-01-01

    Abstract An increasing number of studies have explored genetic associations between the functionally important polymorphisms in estrogen receptor 1 (ESR1) gene and migraine susceptibility. The previously reported associations have nevertheless been inconsistent. The present work incorporating the published data derived from 8 publications was performed to assess the impact of these polymorphisms on incident migraine. Strength of the genetic risk was estimated by means of an odds ratio along with the 95% confidence interval (OR and 95% CI). From the results, we found individuals who harbored the 325-GG genotype, compared with those harboring the CC genotype or CG and CC combined genotypes, had almost 50% greater risk of migraine. The same genetic models showed notable associations in subgroups of Caucasians and migraine with aura (MA). For 594G>A, a moderately increased risk of migraine was seen under AG versus GG. The AA + AG versus GG model, however, showed a borderline association with migraine. Subgroup analyses according to ethnicity and subtype of migraine provided statistical evidence of significantly increased risk of migraine in Caucasians and of a marginal association with MA, respectively. Both 325C>G and 594G>A polymorphisms showed no major effects either in males or in females. Based on the statistical data, we conclude some of the ESR1 gene polymorphisms may have major contributions to the pathogenesis of migraine in Caucasian populations. PMID:26334887

  7. The role of MBL2 gene polymorphism in sepsis incidence

    PubMed Central

    Liu, Lei; Ning, Bo

    2015-01-01

    Aim: This case-control study was aimed to explore the role of mannose-binding lectin 2 (MBL2) gene rs1800450 polymorphism (codon 54 A/B, G230A) in the development of sepsis in Han Chinese. Methods: MBL2 rs1800450 polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). MBL serum level was detected by enzyme-linked immunosorbent assay (ELISA). Associations between rs1800450 and sepsis susceptibility was detected by Chi-square test and represented by odds ratios (ORs) and 95% confidence intervals (CIs). Correlation of rs1800450 genotypes and MBL serum level was assessed using t test. Result: Variant A allele frequency was significantly observed in cases than that in controls, indicating a significant association with the susceptibility of sepsis (OR = 1.979, 95% CI = 1.200-3.262). GA genotype also relate to the onset of sepsis (OR = 2.090, 95% CI = 1.163-3.753). MBL serum concentrations were significantly different between case and control groups (P<0.001). Meanwhile, variant allele carriers had lower serum level compared with wild homozygous (P<0.001). Conclusion: Variant A allele in MBL2 gene rs1800450 polymorphism might increase the risk of sepsis via decrease the MBL serum level. PMID:26823854

  8. Folate: metabolism, genes, polymorphisms and the associated diseases.

    PubMed

    Nazki, Fakhira Hassan; Sameer, Aga Syed; Ganaie, Bashir Ahmad

    2014-01-01

    Folate being an important vitamin of B Complex group in our diet plays an important role not only in the synthesis of DNA but also in the maintenance of methylation reactions in the cells. Folate metabolism is influenced by several processes especially its dietary intake and the polymorphisms of the associated genes involved. Aberrant folate metabolism, therefore, affects both methylation as well as the DNA synthesis processes, both of which have been implicated in the development of various diseases. This paper reviews the current knowledge of the processes involved in folate metabolism and consequences of deviant folate metabolism, particular emphasis is given to the polymorphic genes which have been implicated in the development of various diseases in humans, like vascular diseases, Down's syndrome, neural tube defects, psychiatric disorders and cancers. PMID:24091066

  9. In silico Evaluation of Nonsynonymous Single Nucleotide Polymorphisms in the ADIPOQ Gene Associated with Diabetes, Obesity, and Inflammation

    PubMed Central

    Narayana Swamy, A; Valasala, Harika; Kamma, Sreenivasulu

    2015-01-01

    Background: The human ADIPOQ gene encodes adiponectin protein hormone, which is involved in regulating glucose levels as well as fatty acid breakdown. It is exclusively produced by adipose tissue and abundantly present in the circulation, with concentration of around 0.01% of total serum proteins, with important effect on metabolism. Methods: Most deleterious nonsynonymous single nucleotide polymorphisms in the coding region of the ADIPOQ gene were investigated using SNP databases, and detected nonsynonymous variants were analyzed in silico from the standpoint of relevant protein function and stability by using SIFT, PolyPhen-2, PROVEAN and MUpro, I-Mutant2.0 tools, respectively. Result: A total of 58 nonsynonymous SNPs consisting of 55 missense variations, 3 nonsense variations were found in the ADIPOQ gene. Next, 14 of the 55 missense variants were predicted to be damaging or deleterious by three different software programs (PolyPhen-2, SIFT, and PROVEAN), and 38 of them were predicted to be less stable (I-Mutant 2.0 and MUpro software). Totally, 10 variants out of 55 missense variants were predicted to be both deleterious and reduce protein stability. Additionally, 3 nonsense variants were predicted to produce a truncated ADIPOQ protein. RMSD and total energy were calculated for 4 nsSNPs out of 10 nsSNPs which were both deleterious and showed a decrease in protein stability. Conclusion: rs144526209 has high root-mean-square deviation (RMSD) and lower total energy value compared to the native modeled structure. It was concluded that this nsSNP, potentially functional and polymorphic in the ADIPOQ gene, might be associated with diabetes, obesity, and inflammation. PMID:26306152

  10. Genetic polymorphisms of cytokine genes in type 2 diabetes mellitus

    PubMed Central

    Banerjee, Monisha; Saxena, Madhukar

    2014-01-01

    Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia, dyslipidemia, stroke and several other complications. Various groups all over the world are relentlessly working out the possible role of a vast number of genes associated with type 2 diabetes (T2DM). Inflammation is an important outcome of any kind of imbalance in the body and is therefore an indicator of several diseases, including T2DM. Various ethnic populations around the world show different levels of variations in single nucleotide polymorphisms (SNPs). The present review was undertaken to explore the association of cytokine gene polymorphisms with T2DM in populations of different ethnicities. This will lead to the understanding of the role of cytokine genes in T2DM risk and development. Association studies of genotypes of SNPs present in cytokine genes will help to identify risk haplotype(s) for disease susceptibility by developing prognostic markers and alter treatment strategies for T2DM and related complications. This will enable individuals at risk to take prior precautionary measures and avoid or delay the onset of the disease. Future challenges will be to understand the genotypic interactions between SNPs in one cytokine gene or several genes at different loci and study their association with T2DM. PMID:25126395

  11. ADIPOQ Polymorphisms, Monounsaturated Fatty Acids, and Obesity Risk: The GOLDN Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: To explore whether dietary fat modulates the association of genetic variations at ADIPOQ locus with obesity traits in White US subjects. Methods and Procedures: we genotyped two promoter single nucleotide polymorphisms (SNPs) at adiponectin gene, -11391G>A and -1137C>G, in 1083 participan...

  12. The smaller human VH gene families display remarkably little polymorphism.

    PubMed Central

    Sanz, I; Kelly, P; Williams, C; Scholl, S; Tucker, P; Capra, J D

    1989-01-01

    We report the nucleotide sequence of 30 distinct human VH gene segments from the VHIV, VHV and VHVI gene families. When these sequences were compared to previously published sequences from these smaller human VH families a surprisingly low level of polymorphism was noted. Two VHIV gene segments from unrelated individuals were identical to two previously published VHIV sequences. Five VHV sequences were identical and seven VHVI gene segments were identical. Where differences were found between the sequences, allele specific oligonucleotide probes were used to verify the germline nature of the change and to test for segregation in several large kindreds. These data provide evidence that at least some human VH gene segments are remarkably stable. Images PMID:2511001

  13. Association between apolipoprotein E gene polymorphism and depression.

    PubMed

    Feng, Fang; Lu, Shan-Shan; Hu, Cai-Yun; Gong, Feng-Feng; Qian, Zhen-Zhong; Yang, Hui-Yun; Wu, Yi-Le; Zhao, Yuan-Yuan; Bi, Peng; Sun, Ye-Huan

    2015-08-01

    We performed an updated meta-analysis to obtain a more precise estimation of the relationship between apolipoprotein E (ApoE) gene polymorphism and susceptibility to depression, as previous reports have been inconsistent. Twenty studies with 2286 depression patients and 3845 controls were included. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to assess the association between ApoE gene polymorphism and depression using a random effects model. Results showed a significant association between ApoE gene polymorphism and susceptibility to depression in the overall population (ε2/ε3 genotype versus ε3/ε3: OR 0.76, 95% CI 0.59-0.99). Subgroup analyses indicated an association in the Caucasian population (ε2 allele versus ε3: OR 0.75, 95% CI 0.58-0.97) as well as in late-life depression (LLD) patients (ε3/ε4 genotype versus ε3/ε3: OR 1.34, 95% CI 1.07-1.68, and ε4 allele versus ε3: OR 1.30, 95% CI 1.06-1.59). We concluded that the ε2/ε3 genotype likely provided a protective effect against depression in the overall population and the ε2 allele acted as a protective factor for depression in the Caucasian population while the ε4 allele and ε3/ε4 genotype were associated with an increased risk of depression in the LLD subjects. PMID:25979253

  14. Adiponectin--its role in metabolism and beyond.

    PubMed

    Stefan, N; Stumvoll, M

    2002-09-01

    Adiponectin is a recently identified adipose tissue-derived protein (adipocytokine) with important metabolic effects. It is exclusively expressed in adipose tissue and released into the circulation. Adiponectin expression and/or secretion is increased by insulin like growth factor-1 and ionomycin, and decreased by tumor necrosis factor-alpha, glucocorticoids, beta-adrenergic agonists and cAMP. Data for insulin are somewhat inconclusive. Moreover, adiponectin expression and secretion are increased by activators of peroxisome proliferator-activated receptor (PPAR)-gamma. Besides inhibiting inflammatory pathways, recombinant adiponectin increases insulin sensitivity and improves glucose tolerance in various animal models. This insulin-sensitizing effect appears to be mostly attributable to enhanced suppression of glucose production, but beneficial effects on muscle cannot be excluded. In humans, plasma adiponectin concentrations exceed those of any other hormone by a thousand times; they decrease with obesity and are positively associated with whole-body insulin sensitivity. Therefore, low adiponectin may contribute to the decrease in whole-body insulin sensitivity that accompanies obesity. Furthermore, there is increasing evidence that genetic variants in the adiponectin gene itself and/or in genes encoding adiponectin-regulatory proteins--such as PPAR-gamma--may be associated with hypoadiponectinemia, insulin resistance and type 2 diabetes. This suggests that adiponectin may reflect PPAR-gamma activity in vivo. Finally, reversal or alleviation of hypoadiponectinemia may represent a target for development of drugs improving insulin sensitivity and glucose tolerance. PMID:12384822

  15. Urinary Adiponectin Excretion

    PubMed Central

    von Eynatten, Maximilian; Liu, Dan; Hock, Cornelia; Oikonomou, Dimitrios; Baumann, Marcus; Allolio, Bruno; Korosoglou, Grigorios; Morcos, Michael; Campean, Valentina; Amann, Kerstin; Lutz, Jens; Heemann, Uwe; Nawroth, Peter P.; Bierhaus, Angelika; Humpert, Per M.

    2009-01-01

    OBJECTIVE Markers reliably identifying vascular damage and risk in diabetic patients are rare, and reports on associations of serum adiponectin with macrovascular disease have been inconsistent. In contrast to existing data on serum adiponectin, this study assesses whether urinary adiponectin excretion might represent a more consistent vascular damage marker in type 2 diabetes. RESEARCH DESIGN AND METHODS Adiponectin distribution in human kidney biopsies was assessed by immunohistochemistry, and urinary adiponectin isoforms were characterized by Western blot analysis. Total urinary adiponectin excretion rate was measured in 156 patients with type 2 diabetes who had a history of diabetic nephropathy and 40 healthy control subjects using enzyme-linked immunosorbent assay. Atherosclerotic burden was assessed by common carotid artery intima-media-thickness (IMT). RESULTS A homogenous staining of adiponectin was found on the endothelial surface of glomerular capillaries and intrarenal arterioles in nondiabetic kidneys, whereas staining was decreased in diabetic nephropathy. Low-molecular adiponectin isoforms (∼30–70 kDa) were detected in urine by Western blot analysis. Urinary adiponectin was significantly increased in type 2 diabetes (7.68 ± 14.26 vs. control subjects: 2.91 ± 3.85 μg/g creatinine, P = 0.008). Among type 2 diabetic patients, adiponectinuria was associated with IMT (r = 0.479, P < 0.001) and proved to be a powerful independent predictor of IMT (β = 0.360, P < 0.001) in multivariable regression analyses. In a risk prediction model including variables of the UK Prospective Diabetes Study coronary heart disease risk engine urinary adiponectin, but not the albumin excretion rate, added significant value for the prediction of increased IMT (P = 0.007). CONCLUSIONS Quantification of urinary adiponectin excretion appears to be an independent indicator of vascular damage potentially identifying an increased risk for vascular events. PMID:19509019

  16. [Polymorphism of LW blood group gene in Chinese population].

    PubMed

    Su, Yu-Qing; Yu, Qiong; Liu, Xu; Liang, Yan-Lian; Wei, Tian-Li

    2008-06-01

    In order to study the polymorphism of Landsteiner-Wiener (LW) blood group gene in Chinese population, peripheral blood samples anticoagulated with EDTA from 160 unrelated volunteer blood donors were randomly collected, and genomic DNA were extracted. 160 DNA samples were analyzed for exon 1 of LW gene by direct DNA sequencing, and detected for LWa/LWb allele by improved PCR-SSP genotyping. The results showed that all LW allele in 160 donors were LWa homozygous, and the LWa allele occurred commonly. In conclusion, LWa allele occurs with incidence of 100% of donors in this study, while LWb allele has not been found in Chinese population. PMID:18549656

  17. Do polymorphisms in chemosensory genes matter for human ingestive behavior?

    PubMed Central

    Hayes, John E.; Feeney, Emma L.; Allen, Alissa L.

    2013-01-01

    In the last decade, basic research in chemoreceptor genetics and neurobiology have revolutionized our understanding of individual differences in chemosensation. From an evolutionary perspective, chemosensory variations appear to have arisen in response to different living environments, generally in the avoidance of toxins and to better detect vital food sources. Today, it is often assumed that these differences may drive variable food preferences and choices, with downstream effects on health and wellness. A growing body of evidence indicates chemosensory variation is far more complex than previously believed. However, just because a genetic polymorphism results in altered receptor function in cultured cells or even behavioral phenotypes in the laboratory, this variation may not be sufficient to influence food choice in free living humans. Still, there is ample evidence to indicate allelic variation in TAS2R38 predicts variation in bitterness of synthetic pharmaceuticals (e.g., propylthiouracil) and natural plant compounds (e.g., goitrin), and this variation associates with differential intake of alcohol and vegetables. Further, this is only one of 25 unique bitter taste genes (TAS2Rs) in humans, and emerging evidence suggests other TAS2Rs may also contain polymorphisms that a functional with respect to ingestive behavior. For example, TAS2R16 polymorphisms are linked to the bitterness of naturally occurring plant compounds and alcoholic beverage intake, a TAS2R19 polymorphism predicts differences in quinine bitterness and grapefruit bitterness and liking, and TAS2R31 polymorphisms associate with differential bitterness of plant compounds like aristolochic acid and the sulfonyl amide sweeteners saccharin and acesulfame-K. More critically with respect to food choices, these polymorphisms may vary independently from each other within and across individuals, meaning a monolithic one-size-fits-all approach to bitterness needs to be abandoned. Nor are genetic

  18. Do polymorphisms in chemosensory genes matter for human ingestive behavior?

    PubMed

    Hayes, John E; Feeney, Emma L; Allen, Alissa L

    2013-12-01

    In the last decade, basic research in chemoreceptor genetics and neurobiology have revolutionized our understanding of individual differences in chemosensation. From an evolutionary perspective, chemosensory variations appear to have arisen in response to different living environments, generally in the avoidance of toxins and to better detect vital food sources. Today, it is often assumed that these differences may drive variable food preferences and choices, with downstream effects on health and wellness. A growing body of evidence indicates chemosensory variation is far more complex than previously believed. However, just because a genetic polymorphism results in altered receptor function in cultured cells or even behavioral phenotypes in the laboratory, this variation may not be sufficient to influence food choice in free living humans. Still, there is ample evidence to indicate allelic variation in TAS2R38 predicts variation in bitterness of synthetic pharmaceuticals (e.g., propylthiouracil) and natural plant compounds (e.g., goitrin), and this variation associates with differential intake of alcohol and vegetables. Further, this is only one of 25 unique bitter taste genes (TAS2Rs) in humans, and emerging evidence suggests other TAS2Rs may also contain polymorphisms that a functional with respect to ingestive behavior. For example, TAS2R16 polymorphisms are linked to the bitterness of naturally occurring plant compounds and alcoholic beverage intake, a TAS2R19 polymorphism predicts differences in quinine bitterness and grapefruit bitterness and liking, and TAS2R31 polymorphisms associate with differential bitterness of plant compounds like aristolochic acid and the sulfonyl amide sweeteners saccharin and acesulfame-K. More critically with respect to food choices, these polymorphisms may vary independently from each other within and across individuals, meaning a monolithic one-size-fits-all approach to bitterness needs to be abandoned. Nor are genetic

  19. Association between ERCC5 gene polymorphisms and gastric cancer risk.

    PubMed

    Guo, B W; Yang, L; Zhao, R; Hao, S Z

    2016-01-01

    We investigate the role of ERCC5 gene polymorphisms (rs17655 and rs751402) in the development of gastric cancer in a Chinese population. A total of 142 gastric cancer patients whose diagnoses were confirmed by pathology, and 274 control subjects were recruited from Tangshan Gongren Hospital between March 2013 and March 2015. Genotyping of ERCC5 rs17655 and rs751402 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism. Compared with the control subjects, we found that gastric cancer patients were more likely to be older, smoke tobacco, drink alcohol, and suffer from Helicobacter pylori infection. Using a chi-square test, a significant difference was observed in the distribution ofERCC5 rs751402 genotypes between patient and control groups (chi-square = 7.79, P = 0.02). In addition, unconditional multiple logistic regression analysis revealed that the AA genotype of rs751402 significantly increased gastric cancer risk compared to the GG genotype [odds ratio (OR) = 2.61, 95%CI = 1.23-5.49; P = 0.005]. Moreover, we found that the AA genotype correlated with elevated risk of gastric cancer when compared to the GG+AG genotype under a recessive model (OR = 2.21, 95%CI = 1.11-4.39; P = 0.01). In conclusion, we suggest that the ERCC5 rs751402 polymorphism is associated with development of gastric cancer. PMID:27323183

  20. Leptin receptor gene polymorphisms in severely pre-eclamptic women.

    PubMed

    Rigó, János; Szendei, György; Rosta, Klára; Fekete, Andrea; Bögi, Krisztina; Molvarec, Attila; Rónai, Zsolt; Vér, Agota

    2006-09-01

    Variants of the leptin receptor gene (LEPR) may modulate the effect of elevated serum leptin levels in pre-eclampsia. The aim of our study was to evaluate the LEPR gene polymorphisms Lys109Arg (A109G) and Gln223Arg (A223G) in severely pre-eclamptic women. In a case-control study, we analyzed blood samples from 124 severely pre-eclamptic patients and 107 healthy control women by the polymerase chain reaction-restriction fragment length polymorphism method. The Pearson chi2 test was used to estimate odds ratios (OR) and 95% confidence intervals (CI). The association was adjusted for maternal age, pre-pregnancy body mass index and primiparity with logistic regression analysis. Pregnant women with the LEPR 223G allele (223A/G or 223G/G genotype) had almost double the risk of developing severe pre-eclampsia compared with patients with the 223A/A genotype (adjusted OR = 1.92, 95% CI: 1.07-3.41). Genotype variants of LEPR A109G alone did not affect the risk of severe pre-eclampsia. Haplotype estimation of A109G and A223G polymorphisms of the LEPR gene revealed that the G-A haplotype versus other pooled haplotypes was significantly less common in the pre-eclamptic group (p < 0.01), while the G-G haplotype versus others was overrepresented among severely pre-eclamptic patients (p < 0.01), compared with controls. In conclusion, our data indicate that LEPR A223G polymorphism may individually modify the risk of severe pre-eclampsia. PMID:17071538

  1. Uncoupling protein 2 gene polymorphisms are associated with obesity

    PubMed Central

    2012-01-01

    Background Uncoupling protein 2 (UCP2) gene polymorphisms have been reported as genetic risk factors for obesity and type 2 diabetes mellitus (T2DM). We examined the association of commonly observed UCP2 G(−866)A (rs659366) and Ala55Val (C > T) (rs660339) single nucleotide polymorphisms (SNPs) with obesity, high fasting plasma glucose, and serum lipids in a Balinese population. Methods A total of 603 participants (278 urban and 325 rural subjects) were recruited from Bali Island, Indonesia. Fasting plasma glucose (FPG), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were measured. Obesity was determined based on WHO classifications for adult Asians. Participants were genotyped for G(−866)A and Ala55Val polymorphisms of the UCP2 gene. Results Obesity prevalence was higher in urban subjects (51%) as compared to rural subjects (23%). The genotype, minor allele (MAF), and heterozygosity frequencies were similar between urban and rural subjects for both SNPs. All genotype frequencies were in Hardy-Weinberg equilibrium. A combined analysis of genotypes and environment revealed that the urban subjects carrying the A/A genotype of the G(−866)A SNP have higher BMI than the rural subjects with the same genotype. Since the two SNPs showed strong linkage disequilibrium (D’ = 0.946, r2 = 0.657), a haplotype analysis was performed. We found that the AT haplotype was associated with high BMI only when the urban environment was taken into account. Conclusions We have demonstrated the importance of environmental settings in studying the influence of the common UCP2 gene polymorphisms in the development of obesity in a Balinese population. PMID:22533685

  2. Gene--gene interaction among cytokine polymorphisms influence susceptibility to aggressive periodontitis.

    PubMed

    Scapoli, C; Mamolini, E; Carrieri, A; Guarnelli, M E; Annunziata, M; Guida, L; Romano, F; Aimetti, M; Trombelli, L

    2011-09-01

    Aggressive periodontitis (AgP) is a multifactorial disease. The distinctive aspect of periodontitis is that this disease must deal with a large number of genes interacting with one another and forming complex networks. Thus, it is reasonable to expect that gene-gene interaction may have a crucial role. Therefore, we carried out a pilot case-control study to identify the association of candidate epistatic interactions between genetic risk factors and susceptibility to AgP, by using both conventional parametric analyses and a higher order interactions model, based on the nonparametric Multifactor Dimensionality Reduction algorithm. We analyzed 122 AgP patients and 246 appropriate periodontally healthy individuals, and genotyped 28 polymorphisms, located within 14 candidate genes, chosen among the principal genetic variants pointed out from literature and having a role in inflammation and immunity. Our analyses provided significant evidence for gene--gene interactions in the development of AgP, in particular, present results: (a) indicate a possible role of two new polymorphisms, within SEPS1 and TNFRSF1B genes, in determining host individual susceptibility to AgP; (b) confirm the potential association between of IL-6 and Fc γ- receptor polymorphisms and the disease; (c) exclude an essential contribution of IL-1 cluster gene polymorphisms to AgP in our Caucasian-Italian population. PMID:21593780

  3. Atlantic cod (Gadus morhua) hemoglobin genes: multiplicity and polymorphism

    PubMed Central

    Borza, Tudor; Stone, Cynthia; Gamperl, A Kurt; Bowman, Sharen

    2009-01-01

    Background Hemoglobin (Hb) polymorphism, assessed by protein gel electrophoresis, has been used almost exclusively to characterize the genetic structure of Atlantic cod (Gadus morhua) populations and to establish correlations with phenotypic traits such as Hb oxygen binding capacity, temperature tolerance and growth characteristics. The genetic system used to explain the results of gel electrophoresis entails the presence of one polymorphic locus with two major alleles (HbI-1; HbI-2). However, vertebrates have more than one gene encoding Hbs and recent studies have reported that more than one Hb gene is present in Atlantic cod. These observations prompted us to re-evaluate the number of Hb genes expressed in Atlantic cod, and to perform an in depth search for polymorphisms that might produce relevant phenotypes for breeding programs. Results Analysis of Expressed Sequence Tags (ESTs) led to the identification of nine distinct Hb transcripts; four corresponding to the α Hb gene family and five to the β Hb gene family. To gain insights about the Hb genes encoding these transcripts, genomic sequence data was generated from heterozygous (HbI-1/2) parents and fifteen progeny; five of each HbI type, i.e., HbI-1/1, HbI-1/2 and HbI-2/2. β Hb genes displayed more polymorphism than α Hb genes. Two major allele types (β1A and β1B) that differ by two linked non-synonymous substitutions (Met55Val and Lys62Ala) were found in the β1 Hb gene, and the distribution of these β1A and β1B alleles among individuals was congruent with that of the HbI-1 and HbI-2 alleles determined by protein gel electrophoresis. RT-PCR and Q-PCR analysis of the nine Hb genes indicates that all genes are expressed in adult fish, but their level of expression varies greatly; higher expression of almost all Hb genes was found in individuals displaying the HbI-2/2 electrophoretic type. Conclusion This study indicates that more Hb genes are present and expressed in adult Atlantic cod than previously

  4. Vitamin D receptor gene polymorphisms in breast cancer.

    PubMed

    Buyru, Nur; Tezol, Ayda; Yosunkaya-Fenerci, Elif; Dalay, Nejat

    2003-12-31

    Breast cancer is the leading cause of cancer death among women around the world and its incidence is annually increasing. The vitamin D receptor (VDR) gene is a member of the nuclear receptor superfamily, which is expressed in breast tissue and known to modulate the rate of cell proliferation. Association between the VDR gene polymorphisms and cancer development has been suggested by several studies. However, the relationship between VDR polymorphisms and breast cancer is controversial and has not been confirmed by all studies. The purpose of this study was to investigate the genotype frequencies and association of the VDR Bsm I and Taq I polymorphisms with breast cancer in Turkish patients. In this study, 78 patients with breast cancer and 27 healthy individuals were enrolled. The prevalence of the VDR Taq I and Bsm I alleles and the genotype frequencies in patients with breast cancer was similar to that in the normal population. Our data indicate that no significant differences exist between the patients and control subjects. PMID:14749534

  5. CC chemokine receptor 5 gene polymorphisms in beryllium disease.

    PubMed

    Sato, H; Silveira, L; Spagnolo, P; Gillespie, M; Gottschall, E B; Welsh, K I; du Bois, R M; Newman, L S; Maier, L A

    2010-08-01

    CC chemokine receptor 5 (CCR5) is expressed on type-1 T-helper cells, which are involved in the pathogenesis of the granulomatous lung disease chronic beryllium disease (CBD). CCR5 gene (CCR5) polymorphisms are associated with sarcoidosis severity. The present study explores associations between CCR5 polymorphisms and CBD and its disease progression. Eight CCR5 polymorphisms were genotyped in CBD (n = 88), beryllium sensitisation (BeS; n = 86) and beryllium-exposed nondiseased controls (n = 173) using PCR with sequence-specific primers. Pulmonary function and bronchoalveolar lavage data were examined for associations with genotypes. There were no significant differences in genotype and allele frequency between CBD, BeS individuals and controls. In CBD, associations were found with decline in forced expiratory volume in 1 s and forced vital capacity and the CCR5 -3458 thymidine (T)T genotype (p<0.0001), and an increase in alveolar-arterial oxygen tension difference at rest (p = 0.003) and at maximum exercise (p = 0.01) and the -5663 adenine allele. Increased bronchoalveolar lavage lymphocyte numbers were associated with CCR5 -2459 guanine/-2135T (p = 0.01) only in the combined CBD and BeS group. This is the first study showing that CCR5 polymorphisms are associated with worsening pulmonary function over time in CBD, suggesting that CCR5 is important in the progression of pulmonary function in CBD. Further studies would be useful to clarify the mechanism whereby CCR5 polymorphisms affect progression of CBD. PMID:20075058

  6. Association of TLR and TREM-1 gene polymorphisms with atherosclerosis severity in a Russian population

    PubMed Central

    Kutikhin, Anton G.; Ponasenko, Anastasia V.; Khutornaya, Maria V.; Yuzhalin, Arseniy E.; Zhidkova, Irina I.; Salakhov, Ramil R.; Golovkin, Alexey S.; Barbarash, Olga L.; Barbarash, Leonid S.

    2016-01-01

    Local vascular immune response is primarily initiated via Toll-like receptors (TLRs) and triggering receptor expressed on myeloid cells-1 (TREM-1). We previously showed that certain TLR and TREM-1 gene polymorphisms are associated with coronary artery disease (CAD). Therefore, we hypothesized that these gene polymorphisms are associated with atherosclerosis severity. This study included 292 consecutive patients with CAD who were admitted to the Research Institute for Complex Issues of Cardiovascular Diseases (Kemerovo, Russian Federation) during 2011–2012. Sample genotyping was performed in 96-well format using the TaqMan SNP genotyping assay. We found that C/C genotype of the rs3804099 polymorphism within TLR2 gene and T/T genotype of the rs4711668 polymorphism within TREM-1 gene were significantly associated with severe coronary atherosclerosis while C allele of the rs5743551 polymorphism within TLR1 gene, A/G genotype of the rs4986790 polymorphism and C/T genotype of the rs4986791 polymorphism within TLR4 gene, and C allele of the rs3775073 polymorphism within TLR6 gene were significantly associated with severe noncoronary atherosclerosis. However, A/A genotype of the rs5743810 polymorphism within TLR6 gene was significantly associated with mild noncoronary atherosclerosis. We conclude that certain TLR and TREM-1 gene polymorphisms are significantly associated with atherosclerosis severity in a Russian population. PMID:27200266

  7. Association of TLR and TREM-1 gene polymorphisms with atherosclerosis severity in a Russian population.

    PubMed

    Kutikhin, Anton G; Ponasenko, Anastasia V; Khutornaya, Maria V; Yuzhalin, Arseniy E; Zhidkova, Irina I; Salakhov, Ramil R; Golovkin, Alexey S; Barbarash, Olga L; Barbarash, Leonid S

    2016-09-01

    Local vascular immune response is primarily initiated via Toll-like receptors (TLRs) and triggering receptor expressed on myeloid cells-1 (TREM-1). We previously showed that certain TLR and TREM-1 gene polymorphisms are associated with coronary artery disease (CAD). Therefore, we hypothesized that these gene polymorphisms are associated with atherosclerosis severity. This study included 292 consecutive patients with CAD who were admitted to the Research Institute for Complex Issues of Cardiovascular Diseases (Kemerovo, Russian Federation) during 2011-2012. Sample genotyping was performed in 96-well format using the TaqMan SNP genotyping assay. We found that C/C genotype of the rs3804099 polymorphism within TLR2 gene and T/T genotype of the rs4711668 polymorphism within TREM-1 gene were significantly associated with severe coronary atherosclerosis while C allele of the rs5743551 polymorphism within TLR1 gene, A/G genotype of the rs4986790 polymorphism and C/T genotype of the rs4986791 polymorphism within TLR4 gene, and C allele of the rs3775073 polymorphism within TLR6 gene were significantly associated with severe noncoronary atherosclerosis. However, A/A genotype of the rs5743810 polymorphism within TLR6 gene was significantly associated with mild noncoronary atherosclerosis. We conclude that certain TLR and TREM-1 gene polymorphisms are significantly associated with atherosclerosis severity in a Russian population. PMID:27200266

  8. Gene polymorphisms associated with non-alcoholic fatty liver disease and coronary artery disease: a concise review.

    PubMed

    Li, Xiao-Lin; Sui, Jian-Qing; Lu, Lin-Lin; Zhang, Nan-Nan; Xu, Xin; Dong, Quan-Yong; Xin, Yong-Ning; Xuan, Shi-Ying

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease which represents a wide spectrum of hepatic damage. Several studies have reported that NAFLD is a strong independent risk factor for coronary artery disease (CAD). And patients with NAFLD are at higher risk and suggested undergoperiodic cardiovascular risk assessment. Cardiovascular disease (CVD) is responsible for the main cause of death in patients with NAFLD, and is mostly influenced by genetic factors. Both NAFLD and CAD are heterogeneous disease. Common pathways involved in the pathogenesis of NAFLD and CAD includes insulin resistance (IR), atherogenic dyslipidemia, subclinical inflammation, oxidative stress, etc. Genomic characteristics of these two diseases have been widely studied, further research about the association of these two diseases draws attention. The gene polymorphisms of adiponectin-encoding gene (ADIPOQ), leptin receptor (LEPR), apolipoprotein C3 (APOC3), peroxisome proliferator-activated receptors (PPAR), sterol regulatory elementbinding proteins (SREBP), transmembrane 6 superfamily member 2 (TM6SF2), microsomal triglyceride transfer protein (MTTP), tumor necrosis factors-alpha (TNF-α) and manganese superoxide dismutase (MnSOD) have been reported to be related to NAFLD and CAD. In this review, we aimed to provide an overview of recent insights into the genetic basis of NAFLD and CAD. PMID:26965314

  9. Latitude-correlated genetic polymorphisms: selection or gene flow?

    PubMed

    Ciminelli, B M; Jodice, C; Scozzari, R; Corbo, R M; Nahum, M; Pompei, F; Santachiara-Benerecetti, S A; Santolamazza, C; Morpurgo, G P; Modiano, G

    2000-08-01

    Latitude-correlated polymorphisms can be due to either selection-driven evolution or gene flow. To discriminate between them, we propose an approach that studies subpopulations springing from a single population that have lived for generations at different latitudes and have had a low genetic admixture. These requirements are fulfilled to a large extent by Ashkenazi and Sephardi Jews. The original population lived at a latitude of 35 degrees N, where the Sephardis still live. The Ashkenazis, however, moved to a latitude of 50 degrees N, starting about 10 centuries ago. The present study examines 3 latitude-correlated polymorphisms: PGP, PGM1, and AHSG. We found that PGP*2 and AHSG*2 alleles most likely underwent selection-driven evolution, but that PGM1*ts allele was not similarly affected. Since temperature might have been considered a reasonable selective factor, we also studied a population living at >800 m above sea level from Aosta Valley (Italy). PMID:11048786

  10. Candidate gene polymorphisms for behavioural adaptations during urbanization in blackbirds.

    PubMed

    Mueller, J C; Partecke, J; Hatchwell, B J; Gaston, K J; Evans, K L

    2013-07-01

    Successful urban colonization by formerly rural species represents an ideal situation in which to study adaptation to novel environments. We address this issue using candidate genes for behavioural traits that are expected to play a role in such colonization events. We identified and genotyped 16 polymorphisms in candidate genes for circadian rhythms, harm avoidance and migratory and exploratory behaviour in 12 paired urban and rural populations of the blackbird Turdus merula across the Western Palaearctic. An exonic microsatellite in the SERT gene, a candidate gene for harm avoidance behaviour, exhibited a highly significant association with habitat type in an analysis conducted across all populations. Genetic divergence at this locus was consistent in 10 of the 12 population pairs; this contrasts with previously reported stochastic genetic divergence between these populations at random markers. Our results indicate that behavioural traits related to harm avoidance and associated with the SERT polymorphism experience selection pressures during most blackbird urbanization events. These events thus appear to be influenced by homogeneous adaptive processes in addition to previously reported demographic founder events. PMID:23495914

  11. Association between the vitamin D receptor gene polymorphism and osteoporosis

    PubMed Central

    Wu, Ju; Shang, De-Peng; Yang, Sheng; Fu, Da-Peng; Ling, Hao-Yi; Hou, Shuang-Shuang; Lu, Jian-Min

    2016-01-01

    The influence of the vitamin D receptor (VDR) gene for the risk of osteoporosis remains to be elucidated. The aim of the present study was to understand the distribution of various single-nucleotide polymorphisms (SNPs) within the VDR gene and its association with the risk of osteoporosis. In total, 378 subjects without a genetic relationship were recruited to the study between January 2013 and July 2015. The subjects were divided into three groups, which were the normal (n=234), osteoporosis (n=65) and osteoporosis with osteoporotic fracture (n=79) groups. Three pertinent SNPs of the VDR gene rs17879735 (ApaI, Allele A/a, SNP C>A) were examined with polymerase chain reaction-restriction fragment length polymorphism. The bone mineral density (BMD) of the lumbar spine (L2-L4), femoral neck, Ward's and Tro was measured using dual-energy X-ray absorptiometry. The distributions of genotype frequencies aa, AA and Aa were 48.68, 42.86 and 8.46%, separately. Following analysis of each site, BMD, body mass index (BMI) and age, BMD for each site was negatively correlated with age (P<0.01) and positively correlated with BMI (P<0.01). Correction analysis revealed that there were significant differences in the Ward's triangle BMD among each genotype (P<0.05), in which the aa genotype exhibited the lower BMD (P<0.05). No significant difference was identified among the different genotypes in the occurrence of osteoporosis with osteoporotic fracture (P>0.05). In conclusion, these indicated that the VDR gene ApaI polymorphisms had an important role in the osteoporosis risk. PMID:27446548

  12. Correlations Between Leptin Gene Polymorphisms 223 A/G, 1019 G/A, 492 G/C, 976 C/A, and Anthropometrical and Biochemical Parameters in Children With Obesity

    PubMed Central

    Mărginean, Cristina Oana; Mărginean, Claudiu; Voidăzan, Septimiu; Meliţ, Lorena; Crauciuc, Andrei; Duicu, Carmen; Bănescu, Claudia

    2016-01-01

    Abstract The aim of this study was to establish the manner in which the LEPR 223, 1019, 492, and 976 gene polymorphisms influence child obesity. We performed a prospective case-control study on 264 hospitalized children from Romania (Nutrichild study) whom we divided into 2 groups: Group I —143 controls and Group II—121 obese children. The 2 groups were evaluated regarding the anthropometry (MUAC, TST, H/L, hip, and abdominal circumference), paraclinical results (protein, leptin, adiponectin, TNF alfa, IL 6, IL 8, VEGF, protein, albumin) and LEPR 223, 1019, 492, and 976 gene polymorphisms. We noticed that the most frequent genotypes in obese children were AG+GG for LEPR 223 gene (P = 0.0001) and GA+AA for LEPR 1019 gene (P = 0.0001), whereas LEPR 492 and LEPR 976 gene polymorphisms did not correlate with obesity. MUAC, TST, H/L, leptin, and adiponectin were correlated with the GG genotype of the LEPR 223 gene, whereas the AG genotype correlated with TNF alpha and serum IL 8. Hip and abdominal perimeters were higher in LEPR 1019 AA genotype carriers, whereas TNF alpha and IL 6 correlated with the GG genotype of the same gene. Obesity did not correlate with protein serum levels. We observed that obesity is more frequent in children with LEPR 223 AG+GG and LEPR 1019 GA+AA genotypes. In obese children LEPR 223/492/1019 AG/GG/GA, GG/GG/GA and AA/GG/GA combined genotypes are more frequent. PMID:27015185

  13. The importance of MDR1 gene polymorphisms for tacrolimus dosage.

    PubMed

    Kravljaca, Milica; Perovic, Vladimir; Pravica, Vera; Brkovic, Voin; Milinkovic, Marija; Lausevic, Mirjana; Naumovic, Radomir

    2016-02-15

    Polymorphisms of the multi drug resistance (MDR1) gene cause variability in P-glycoprotein mediated metabolism of tacrolimus. The aim of this study was to examine the relationship between MDR1 gene single nucleotide polymorphisms (SNPs) and their haplotypes with dosage of tacrolimus in kidney transplant recipients who were cytochrome (CYP) 3A5*3 homozygotes. This study included 91 kidney transplant recipients followed two years after transplantation. Detection and analysis of MDR1 gene polymorphisms in positions C1236T, G2677T/A and C3435T were performed using PCR method. Patients with variant alleles for SNPs G2677T/A and C3435T required higher doses of tacrolimus and had a lower level/dose (L/D) ratio than patients with wild alleles or heterozygotes. That difference was the most obvious for SNP G2677T/A where TT homozygotes required significantly higher doses of tacrolimus during whole follow-up. Their L/D was significantly lower in the first month after transplantation. Recipients with CTT/TTT haplotype also had lower L/D than those with CGC/TTT and CGC/CGC, significantly in the 10th and 20th days after transplantation respectively (p<0.05). Our results demonstrate that TT homozygotes at positions G2677T/A and C3435T required a higher tacrolimus dose than those with wild alleles or heterozygotes. It may be helpful in the prevention of tacrolimus nephrotoxicity early after transplantation. PMID:26705892

  14. TNFα gene polymorphisms in the pathogenesis of acne vulgaris.

    PubMed

    Szabó, Kornélia; Tax, Gábor; Teodorescu-Brinzeu, Dragos; Koreck, Andrea; Kemény, Lajos

    2011-01-01

    Inflammation plays an important role in acne pathogenesis, and pro-inflammatory cytokines are key factors in these events. Tumor necrosis factor alpha (TNFα) is a central molecule coded by a gene that shows high level of genetic polymorphisms especially in its promoter region. Single nucleotide polymorphisms (SNPs) of the TNFα gene have been shown to be associated with an increased risk to develop chronic inflammatory diseases. In order to find out if known TNFα regulatory SNPs (-1031T>C, -857C>T, -863C>A, -308G>A, -238G>A) have a role in the development of the inflammatory reactions in acne vulgaris, we analyzed our genomic collection in a retrospective case-control study using the PCR-RFLP method, and we compared the resulting genotype and allele frequencies. There were no significant differences in the observed genotype or allele frequencies between the control and acne group in case of the -1031, -863, -238 SNPs; however, the TNFα -857 minor T allele was found to act as a protective factor in our study population in acne, and a higher occurrence of the minor -308 A allele in female acne patients was also noted. Genetic variants of the TNFα gene may affect the risk of acne vulgaris. Our results can help to elucidate the molecular events leading to acne development. PMID:20386917

  15. The Joint Effects of Body Mass Index and MAOA Gene Polymorphism on Depressive Symptoms.

    PubMed

    Liu, Yangyang

    2015-07-01

    The objective of the present study was to examine the joint effects of the body mass index and the MAOA gene polymorphism on depressive symptoms. In two independent Chinese samples, we measured adolescents' depressive symptoms and body mass index and collected their DNA. The results indicated that the main effects of the MAOA gene polymorphism on depressive symptoms were significant. However, the main effects of body mass index and the interaction of the MAOA gene polymorphism and body mass index on depressive symptoms were not significant. By using Chinese adolescents, this study confirmed that the MAOA gene polymorphism directly influenced adolescents' depressive symptoms. PMID:26207137

  16. The Joint Effects of Body Mass Index and MAOA Gene Polymorphism on Depressive Symptoms

    PubMed Central

    2015-01-01

    The objective of the present study was to examine the joint effects of the body mass index and the MAOA gene polymorphism on depressive symptoms. In two independent Chinese samples, we measured adolescents' depressive symptoms and body mass index and collected their DNA. The results indicated that the main effects of the MAOA gene polymorphism on depressive symptoms were significant. However, the main effects of body mass index and the interaction of the MAOA gene polymorphism and body mass index on depressive symptoms were not significant. By using Chinese adolescents, this study confirmed that the MAOA gene polymorphism directly influenced adolescents' depressive symptoms. PMID:26207137

  17. Hodgkin Lymphoma Risk: Role of Genetic Polymorphisms and Gene-Gene Interactions in DNA repair pathways

    PubMed Central

    Monroy, Claudia M.; Cortes, Andrea C.; Lopez, Mirtha; Rourke, Elizabeth; Etzel, Carol J.; Younes, Anas; Strom, Sara S.; El-Zein, Randa

    2011-01-01

    DNA repair variants may play a potentially important role in an individual’s susceptibility to developing cancer. Numerous studies have reported the association between genetic single nucleotide polymorphisms (SNPs) in DNA repair genes and different types of hematologic cancers. However, to date, the effects of such SNPs on modulating Hodgkin Lymphoma (HL) risk have not yet been investigated. We hypothesized that gene-gene interaction between candidate genes in Direct Reversal, Nucleotide excision repair (NER), Base excision repair (BER) and Double strand break (DSB) pathways may contribute to susceptibility to HL. To test this hypothesis, we conducted a study on 200 HL cases and 220 controls to assess associations between HL risk and 21 functional SNPs in DNA repair genes. We evaluated potential gene-gene interactions and the association of multiple polymorphisms in a chromosome region using a multi-analytic strategy combining logistic regression, multi-factor dimensionality reduction and classification and regression tree approaches. We observed that, in combination, allelic variants in the XPC Ala499Val, NBN Glu185Gln, XRCC3 Thr241Me, XRCC1 Arg194Trp and XRCC1 399Gln polymorphisms modify the risk for developing HL. Moreover, the cumulative genetic risk score revealed a significant trend where the risk for developing HL increases as the number of adverse alleles in BER and DSB genes increase. These findings suggest that DNA repair variants in BER and DSB pathways may play an important role in the development of HL. PMID:21374732

  18. Polymorphism of the myostatin gene and its association with growth traits in chicken.

    PubMed

    Bhattacharya, T K; Chatterjee, R N

    2013-04-01

    An experiment was carried out on myostatin gene with the objectives of identification of polymorphism in the myostatin gene and estimation of the effect of polymorphism on growth traits in chickens. Single-stranded conformation polymorphism followed by sequencing was performed to reveal polymorphism of the gene. A total of 13 haplotypes were observed across 3 chicken lines (PB-1 and CB as broiler lines and IWI as the layer line). Myostatin haplogroups had a significant effect on BW at 28, 42, and 49 d of age in the PB-1 line. The significant association of haplogroups was observed with BW at d 14 and 49 in the CB line. In the IWI layer line, the myostatin gene was polymorphic but had no significant association with growth traits. It is concluded that the myostatin gene was polymorphic and had a significant effect on growth traits in broiler chickens. PMID:23472013

  19. Polymorphisms in mitochondrial genes and prostate cancer risk

    PubMed Central

    Wang, Liang; McDonnell, Shannon K.; Hebbring, Scott J.; Cunningham, Julie M.; Sauver, Jennifer St; Cerhan, James R.; Isaya, Grazia; Schaid, Daniel J.; Thibodeau, Stephen N.

    2009-01-01

    The mitochondrion, conventionally thought to be an organelle specific to energy metabolism, is in fact multi-functional and implicated in many diseases, including cancer. To evaluate whether mitochondria-related genes are associated with increased risk for prostate cancer, we genotyped 24 single nucleotide polymorphisms (SNPs) within the mitochondrial genome (mtSNPs) and 376 tagSNPs localized to 78 nuclear-encoded mitochondrial genes. The tagSNPs were selected to achieve ≥80% coverage based on linkage disequilibrium. We compared allele and haplotype frequencies in ~1000 prostate cancer cases with ~500 population controls. An association with prostate cancer was not detected for any of the mtSNPs individually or for 10 mitochondrial common haplotypes when evaluated using a global score statistic. For the nuclear-encoded genes, none of the tagSNPs were significantly associated with prostate cancer after adjusting for multiple testing. Nonetheless, we evaluated unadjusted p-values by comparing our results with those from the CGEMS phase I data set. Seven tagSNPs had unadjusted p-values ≤ 0.05 in both our data and in CGEMS (two SNPs were identical and five were in strong linkage disequilibrium with CGEMS SNPs). These seven SNPs (rs17184211, rs4147684, rs4233367, rs2070902, rs3829037, rs7830235, and rs1203213) are located in genes MTRR, NDUFA9, NDUFS2, NDUFB9 and COX7A2, respectively. Five of the seven SNPs were further included in the CGEMS phase II study, however, none of the findings for these were replicated. Overall, these results suggest that polymorphisms in the mitochondrial genome and those in the nuclear encoded mitochondrial genes evaluated are not substantial risk factors for prostate cancer. PMID:19064571

  20. Coeliac disease-associated polymorphisms influence thymic gene expression.

    PubMed

    Amundsen, S S; Viken, M K; Sollid, L M; Lie, B A

    2014-09-01

    Significant associations between coeliac disease (CD) and single nucleotide polymorphisms (SNPs) distributed over 40 genetic regions have been established. The majority of these SNPs are non-coding and 20 SNPs were, by expression quantitative trait loci (eQTL) analysis, found to harbour cis regulatory potential in peripheral blood mononuclear cells (PBMC). Almost all regions contain genes with an immunological relevant function, of which many act in the same biological pathways. One such pathway is T-cell development in the thymus, a pathway previously not explored in CD pathogenesis. The aim of our study was to explore the regulatory potential of the CD-associated SNPs (n=50) by eQTL analysis in thymic tissue from 42 subjects. In total, 43 nominal significant (P<0.05) eQTLs were found within 24 CD-associated chromosomal regions, corresponding to 27 expression-altering SNPs (eSNPs) and 40 probes (eProbes) that represents 39 unique genes (eGenes). Nine significant probe-SNP pairs (corresponding to 8 eSNPs and 7 eGenes) overlapped with previous findings in PBMC (rs12727642-PARK7, rs296547-DDX59, rs917997-IL18RAP, rs842647-AHSA2, rs13003464-AHSA2, rs6974491-ELMO1, rs2074404-NSF (two independent probes) and rs2298428-UBE2L3). When compared across more tissues, we found that 14 eQTLs could represent potentially novel thymus-specific eQTLs. This implies that CD risk polymorphisms could affect gene regulation in thymus. PMID:24871462

  1. Polymorphic variation as a driver of differential neuropeptide gene expression.

    PubMed

    Quinn, John P; Warburton, Alix; Myers, Paul; Savage, Abigail L; Bubb, Vivien J

    2013-12-01

    The regulation of neuropeptide gene expression and their receptors in a tissue specific and stimulus inducible manner will determine in part behaviour and physiology. This can be a dynamic process resulting from short term changes in response to the environment or long term modulation imposed by epigenetically determined mechanisms established during life experiences. The latter underpins what is termed 'nature and nurture, or 'gene×environment interactions'. Dynamic gene expression of neuropeptides or their receptors is a key component of signalling in the CNS and their inappropriate regulation is therefore a predicted target underpinning psychiatric disorders and neuropathological processes. Finding the regulatory domains within our genome which have the potential to direct gene expression is a difficult challenge as 98% of our genome is non-coding and, with the exception of proximal promoter regions, such elements can be quite distant from the gene that they regulate. This review will deal with how we can find such domains by addressing both the most conserved non-exonic regions in the genome using comparative genomics and the most recent or constantly evolving DNA such as repetitive DNA or retrotransposons. We shall also explore how polymorphic changes in such domains can be associated with CNS disorders by altering the appropriate gene expression patterns which maintain normal physiology. PMID:24210140

  2. Association between Polymorphisms in the TSHR Gene and Graves' Orbitopathy

    PubMed Central

    Jurecka-Lubieniecka, Beata; Ploski, Rafal; Kula, Dorota; Szymanski, Konrad; Bednarczuk, Tomasz; Ambroziak, Urszula; Hasse-Lazar, Kornelia; Hyla-Klekot, Lidia; Tukiendorf, Andrzej; Kolosza, Zofia; Jarzab, Barbara

    2014-01-01

    Background Graves' orbitopathy (GO) as well as Graves' disease (GD) hyperthyroidism originate from an autoimmune reaction against the common auto-antigen, thyroid-stimulating hormone receptor (TSHR). GO phenotype is associated with environmental risk factors, mainly nicotinism, as well as genetic risk factors which initiate an immunologic reaction. In some patients GO is observed before diagnosis of GD hyperthyroidism, while it can also be observed far after diagnosis. The intensity of GO symptoms varies greatly in these patients. Thus, the pathogenesis of GD and GO may correlate with different genetic backgrounds, which has been confirmed by studies of correlations between GO and polymorphisms in cytokines involved in orbit inflammation. The aim of our analysis was to assess genetic predisposition to GO in young patients (age of diagnosis ≤30 years of age), for whom environmental effects had less time to influence outcomes than in adults. Methods 768 GD patients were included in the study. 359 of them had clinically evident orbitopathy (NOSPECS ≥2). Patients were stratified by age at diagnosis. Association analyses were performed for genes with a known influence on development of GD - TSHR, HLA-DRB1, cytotoxic T-lymphocyte antigen 4 (CTLA4) and lymphoid protein tyrosine phosphatase (PTPN22). Results The rs179247 TSHR polymorphism was associated with GO in young patients only. In young GO-free patients, allele A was statistically more frequent and homozygous carriers had a considerable lower risk of disease incidence than patients with AG or GG genotypes. Those differences were not found in either elderly patients or the group analyzed as a whole. Conclusions Allele A of the rs179247 polymorphism in the TSHR gene is associated with lower risk of GO in young GD patients. PMID:25061884

  3. Bovine gene polymorphisms related to fat deposition and meat tenderness.

    PubMed

    Fortes, Marina R S; Curi, Rogério A; Chardulo, Luis Artur L; Silveira, Antonio C; Assumpção, Mayra E O D; Visintin, José Antonio; de Oliveira, Henrique N

    2009-01-01

    Leptin, thyroglobulin and diacylglycerol O-acyltransferase play important roles in fat metabolism. Fat deposition has an influence on meat quality and consumers' choice. The aim of this study was to determine allele and genotype frequencies of polymorphisms of the bovine genes, which encode leptin (LEP), thyroglobulin (TG) and diacylglycerol O-acyltransferase (DGAT1). A further objective was to establish the effects of these polymorphisms on meat characteristics. We genotyped 147 animals belonging to the Nelore (Bos indicus), Canchim (5/8 Bos taurus + 3/8 Bos indicus), Rubia Gallega X Nelore (1/2 Bos taurus + 1/2 Bos indicus), Brangus Three-way cross (9/16 Bos taurus + 7/16 Bos indicus) and Braunvieh Three-way cross (3/4 Bos taurus + 1/4 Bos indicus) breeds. Backfat thickness, total lipids, marbling score, ribeye area and shear force were fitted, using the General Linear Model (GLM) procedure of the SAS software. The least square means of genotypes and genetic groups were compared using Tukey's test. Allele frequencies vary among the genetic groups, depending on Bos indicus versus Bos taurus influence. The LEP polymorphism segregates in pure Bos indicus Nelore animals, which is a new finding. The T allele of TG is fixed in Nelore, and DGAT1 segregates in all groups, but the frequency of allele A is lower in Nelore animals. The results showed no association between the genotypes and traits studied, but a genetic group effect on these traits was found. So, the genetic background remains relevant for fat deposition and meat tenderness, but the gene markers developed for Bos taurus may be insufficient for Bos indicus. PMID:21637649

  4. Bovine gene polymorphisms related to fat deposition and meat tenderness

    PubMed Central

    2009-01-01

    Leptin, thyroglobulin and diacylglycerol O-acyltransferase play important roles in fat metabolism. Fat deposition has an influence on meat quality and consumers' choice. The aim of this study was to determine allele and genotype frequencies of polymorphisms of the bovine genes, which encode leptin (LEP), thyroglobulin (TG) and diacylglycerol O-acyltransferase (DGAT1). A further objective was to establish the effects of these polymorphisms on meat characteristics. We genotyped 147 animals belonging to the Nelore (Bos indicus), Canchim (5/8 Bos taurus + 3/8 Bos indicus), Rubia Gallega X Nelore (1/2 Bos taurus + 1/2 Bos indicus), Brangus Three-way cross (9/16 Bos taurus + 7/16 Bos indicus) and Braunvieh Three-way cross (3/4 Bos taurus + 1/4 Bos indicus) breeds. Backfat thickness, total lipids, marbling score, ribeye area and shear force were fitted, using the General Linear Model (GLM) procedure of the SAS software. The least square means of genotypes and genetic groups were compared using Tukey's test. Allele frequencies vary among the genetic groups, depending on Bos indicus versus Bos taurus influence. The LEP polymorphism segregates in pure Bos indicus Nelore animals, which is a new finding. The T allele of TG is fixed in Nelore, and DGAT1 segregates in all groups, but the frequency of allele A is lower in Nelore animals. The results showed no association between the genotypes and traits studied, but a genetic group effect on these traits was found. So, the genetic background remains relevant for fat deposition and meat tenderness, but the gene markers developed for Bos taurus may be insufficient for Bos indicus. PMID:21637649

  5. MicroRNA-421 Gene Polymorphism in Gastric Carcinoma.

    PubMed

    Jin, Xin; Yu, Nong

    2016-01-01

    BACKGROUND As a common malignant tumor, gastric carcinoma requires early diagnosis to improve treatment efficacy. MicroRNA (miR) molecules have highly conserved nucleotide sequences and can negatively regulate target gene expression at the translational level. miR-421 has been suggested to be related with gastric cancer occurrence. The gene polymorphism of miR-421, however, has not been reported. This study thus investigated the G/C polymorphism of miR-421 and its role in progression and prognosis of gastric cancer. MATERIAL AND METHODS A total of 96 gastric cancer patients were recruited in this study and tumor samples were collected from surgical resection. Single-nucleotide polymorphism (SNP) of miR-421 was determined by DNA sequencing for analyzing the correlation between lymph node metastasis and miR-421 genotypes. Logistic regression analysis was used to determine the relationship between genotype and risk factors of gastric cancer. Kaplan-Meier survival analysis was also performed to compare GG and GC carriers. RESULTS Differential expression patterns existed between gastric cancer tissues and normal gastric mucosa. Logistic regression analysis showed GC and GG genotypes were risk factors for gastric cancer. Patients with lymph node metastasis had higher GG genotype frequency compared to those without metastasis. In survival analysis, GG carriers had shorter survival time than GC carriers. Furthermore, GG genotype was correlated with tumor prognosis (p<0.05). CONCLUSIONS G allele of miR-421 is a risk factor for gastric cancer. GG genotype is correlated with lymph node metastasis and prognosis, indicating it is a risk factor for gastric cancer. PMID:27133200

  6. Review: adiponectin in retinopathy.

    PubMed

    Fu, Zhongjie; Gong, Yan; Löfqvist, Chatarina; Hellström, Ann; Smith, Lois E H

    2016-08-01

    Neovascular eye diseases are a major cause of blindness including retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration in which new vessel formation is driven by hypoxia or metabolic abnormalities affecting the fuel supply. White-adipose-tissue derived adipokines such as adiponectin modulate metabolic responses. Increasing evidence shows that lack of adiponectin may result in retinal neovascularization. Activation of the adiponectin pathway may in turn restore energy metabolism, to suppress the drive for compensatory but ultimately pathological neovessels of retinopathy. In this review, we will summarize our current knowledge of the role of adiponectin in eye diseases of premature infants, diabetic patients as well as the elderly. Further investigations in this field are likely to lead to new preventative approaches for these diseases. PMID:27155572

  7. The role of ERBB2 gene polymorphisms in leprosy susceptibility.

    PubMed

    Rêgo, Jamile Leão; Oliveira, Joyce Moura; Santana, Nadja de Lima; Machado, Paulo Roberto Lima; Castellucci, Léa Cristina

    2015-01-01

    Mycobacterium leprae infects skin and peripheral nerves causing deformities and disability. The M. leprae bacterium binds to ErbB2 on the Schwann cell surface causing demyelination and favoring spread of the bacilli and causing nerve injury. Polymorphisms at the ERBB2 gene were previously investigated as genetic risk factors for leprosy in two Brazilian populations but with inconsistent results. Herein we extend the analysis of ERBB2 variants to a third geographically distinct population in Brazil. Our results show that there is no association between the genotyped SNPs and the disease (p>0.05) in this population. A gene set or pathway analysis under the genomic region of ERBB2 will be necessary to clarify its regulation under M. leprae stimulus. PMID:25636184

  8. Phosphodiesterase 4D gene polymorphisms in sudden sensorineural hearing loss.

    PubMed

    Chien, Chen-Yu; Tai, Shu-Yu; Wang, Ling-Feng; Hsi, Edward; Chang, Ning-Chia; Wang, Hsun-Mo; Wu, Ming-Tsang; Ho, Kuen-Yao

    2016-09-01

    The phosphodiesterase 4D (PDE4D) gene has been reported as a risk gene for ischemic stroke. The vascular factors are between the hypothesized etiologies of sudden sensorineural hearing loss (SSNHL), and this genetic effect might be attributed for its role in SSNHL. We hypothesized that genetic variants of the PDE4D gene are associated with susceptibility to SSNHL. We conducted a case-control study with 362 SSNHL cases and 209 controls. Three single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan technology. Hardy-Weinberg equilibrium (HWE) was tested for each SNP, and genetic effects were evaluated according to three inheritance modes. We carried out sex-specific analysis to analyze the overall data. All three SNPs were in HWE. When subjects were stratified by sex, the genetic effect was only evident in females but not in males. The TT genotype of rs702553 exhibited an adjusted odds ratio (OR) of 3.83 (95 % confidence interval = 1.46-11.18) (p = 0.006) in female SSNHL. The TT genotype of SNP rs702553 was associated with female SSNHL under the recessive model (p = 0.004, OR 3.70). In multivariate logistic regression analysis, TT genotype of rs702553 was significantly associated with female SSNHL (p = 0.0043, OR 3.70). These results suggest that PDE4D gene polymorphisms influence the susceptibility for the development of SSNHL in the southern Taiwanese female population. PMID:26521189

  9. Polymorphism in the interferon-alpha gene family.

    PubMed Central

    Golovleva, I.; Kandefer-Szerszen, M.; Beckman, L.; Lundgren, E.

    1996-01-01

    A pronounced genetic polymorphism of the interferon type I gene family has been assumed on the basis of RFLP analysis of the genomic region as well as the large number of sequences published compared to the number of loci. However, IFNA2 is the only locus that has been carefully analyzed concerning gene frequency, and only naturally occurring rare alleles have been found. We have extended the studies on a variation of expressed sequences by studying the IFNA1, IFNA2, IFNA10, IFNA13, IFNA14, and IFNA17 genes. Genomic white-blood-cell DNA from a population sample of blood donors and from a family material were screened by single-nucleotide primer extension (allele-specific primer extension) of PCR fragments. Because of sequence similarities, in some cases "nested" PCR was used, and, when applicable, restriction analysis or control sequencing was performed. All individuals carried the interferon-alpha 1 and interferon-alpha 13 variants but not the LeIF D variant. At the IFNA2 and IFNA14 loci only one sequence variant was found, while in the IFNA10 and IFNA17 groups two alleles were detected in each group. The IFNA10 and IFNA17 alleles segregated in families and showed a close fit to the Hardy-Weinberg equilibrium. There was a significant linkage disequilibrium between IFNA10 and IFNA17 alleles. The fact that the extent of genetic polymorphism was lower than expected suggests that a majority of the previously described gene sequences represent nonpolymorphic rare mutants that may have arisen in tumor cell lines. Images Figure 1 Figure 2 Figure 3 PMID:8751858

  10. Association of VMAT2 gene polymorphisms with alcohol dependence.

    PubMed

    Fehr, Christoph; Sommerlad, Daniel; Sander, Thomas; Anghelescu, Ion; Dahmen, Norbert; Szegedi, Armin; Mueller, Christiana; Zill, Peter; Soyka, Michael; Preuss, Ulrich W

    2013-08-01

    Alcohol-related diseases cause significant harm in the western world. Up to 65 % of the phenotypic variance is genetically determined. Few candidate genes have been identified, comprising ADH4, ALDH2, COMT, CRHR1, DAT (SLC6A3), GABRA2 and MAOA. While abnormalities in the dopaminergic mesolimbic reward system are considered important mediators of alcoholism, studies analyzing variants of dopamine receptors showed conflicting results. Other modulators of the reward system are synaptosomal genes. Among candidate genes, polygenic variants of the Vesicular Monamine Transporter 2 (VMAT2) gene locus associated with alterations of drinking behavior were published. These variants comprise single nucleotide polymorphisms (SNPs) within the promoter region and the open reading frame. In this study, we confirm the association of VMAT2 SNP rs363387 (allelic association: p = 0.015) with alcohol dependence. This SNP defines several haplotypes including up to four SNPs (minimal p = 0.0045). In addition, numeric effects in the subgroups of males and patients with positive family history were found. We suggest that several rs363387 T-allele containing haplotypes increase the risk of alcohol dependence (OR 1.53), whereas G-allele containing haplotypes confer protection against alcohol dependence. Taken together, there is supporting evidence for a contribution of VMAT2 gene variants to phenotypes of alcohol dependence. PMID:23504072

  11. Genetic variants in adiponectin and blood pressure responses to dietary sodium or potassium interventions: a family-based association study.

    PubMed

    Chu, C; Wang, Y; Ren, K-Y; Yan, D-Y; Guo, T-S; Zheng, W-L; Yuan, Z-Y; Mu, J-J

    2016-09-01

    Previous studies have shown that genetic factors might have an important role in blood pressure (BP) responses to dietary salt or potassium intake. The aim of this study was to assess the association of common genetic variants of the adiponectin gene with BP responses to controlled dietary sodium or potassium interventions. Subjects (n=334) from 124 families in rural areas of Northern China were recruited. After a 3-day baseline observation, participants sequentially maintained a 7-day low-sodium diet (NaCl, 3 g per day; or sodium, 51.3 mmol per day), followed by a 7-day high-sodium diet (NaCl, 18 g per day; or sodium, 307.8 mmol per day) and a 7-day high-sodium plus potassium supplementation intervention (KCl, 4.5 g per day; or potassium, 60 mmol per day). A total of seven single nucleotide polymorphisms (SNPs) in the adiponectin gene were selected as the study sites. After adjustment for multiple testing, the adiponectin SNP rs16861205 was significantly associated with the diastolic BP (DBP) response to low-salt intervention, and the DBP and mean arterial pressure (MAP) responses to high-salt intervention (P=0.028, 0.023 and 0.027, respectively). SNP rs822394 was associated with the DBP and MAP responses to low-salt intervention and the DBP response to high-salt intervention (P=0.023, 0.030 and 0.033 respectively). Meanwhile, significant association also existed between SNP rs16861194 and the systolic BP response to potassium supplementation intervention (P=0.026). In addition, SNP rs822394 was significantly associated with basal DBP after adjustment for multiple testing (P=0.033). Our study indicated that the genetic polymorphisms in the adiponectin gene are significantly associated with BP responses to dietary sodium and potassium intake. PMID:27011258

  12. Genetic variants in adiponectin and blood pressure responses to dietary sodium or potassium interventions: a family-based association study

    PubMed Central

    Chu, C; Wang, Y; Ren, K-y; Yan, D-y; Guo, T-s; Zheng, W-l; Yuan, Z-y; Mu, J-j

    2016-01-01

    Previous studies have shown that genetic factors might have an important role in blood pressure (BP) responses to dietary salt or potassium intake. The aim of this study was to assess the association of common genetic variants of the adiponectin gene with BP responses to controlled dietary sodium or potassium interventions. Subjects (n=334) from 124 families in rural areas of Northern China were recruited. After a 3-day baseline observation, participants sequentially maintained a 7-day low-sodium diet (NaCl, 3 g per day; or sodium, 51.3 mmol per day), followed by a 7-day high-sodium diet (NaCl, 18 g per day; or sodium, 307.8 mmol per day) and a 7-day high-sodium plus potassium supplementation intervention (KCl, 4.5 g per day; or potassium, 60 mmol per day). A total of seven single nucleotide polymorphisms (SNPs) in the adiponectin gene were selected as the study sites. After adjustment for multiple testing, the adiponectin SNP rs16861205 was significantly associated with the diastolic BP (DBP) response to low-salt intervention, and the DBP and mean arterial pressure (MAP) responses to high-salt intervention (P=0.028, 0.023 and 0.027, respectively). SNP rs822394 was associated with the DBP and MAP responses to low-salt intervention and the DBP response to high-salt intervention (P=0.023, 0.030 and 0.033 respectively). Meanwhile, significant association also existed between SNP rs16861194 and the systolic BP response to potassium supplementation intervention (P=0.026). In addition, SNP rs822394 was significantly associated with basal DBP after adjustment for multiple testing (P=0.033). Our study indicated that the genetic polymorphisms in the adiponectin gene are significantly associated with BP responses to dietary sodium and potassium intake. PMID:27011258

  13. Sleep fragmentation during late gestation induces metabolic perturbations and epigenetic changes in adiponectin gene expression in male adult offspring mice.

    PubMed

    Khalyfa, Abdelnaby; Mutskov, Vesco; Carreras, Alba; Khalyfa, Ahamed A; Hakim, Fahed; Gozal, David

    2014-10-01

    Sleep fragmentation (SF) is a common condition among pregnant women, particularly during late gestation. Gestational perturbations promote the emergence of adiposity and metabolic disease risk in offspring, most likely through epigenetic modifications. Adiponectin (AdipoQ) expression inversely correlates with obesity and insulin resistance. The effects of SF during late gestation on metabolic function and AdipoQ expression in visceral white adipose tissue (VWAT) of offspring mice are unknown. Male offspring mice were assessed at 24 weeks after dams were exposed to SF or control sleep during late gestation. Increased food intake, body weight, VWAT mass, and insulin resistance, with reductions in AdipoQ expression in VWAT, emerged in SF offspring. Increased DNMT3a and -b and global DNA methylation and reduced histone acetyltransferase activity and TET1, -2, and -3 expression were detected in VWAT of SF offspring. Reductions in 5-hydroxymethylcytosine and H3K4m3 and an increase in DNA 5-methylcytosine and H3K9m2 in the promoter and enhancer regions of AdipoQ emerged in adipocytes from VWAT and correlated with AdipoQ expression. SF during late gestation induces epigenetic modifications in AdipoQ in male offspring mouse VWAT adipocytes along with a metabolic syndrome-like phenotype. Thus, altered gestational environments elicited by SF impose the emergence of adverse, long-lasting metabolic consequences in the next generation. PMID:24812424

  14. Gene polymorphisms and increased DNA damage in morbidly obese women.

    PubMed

    Luperini, B C O; Almeida, D C; Porto, M P; Marcondes, J P C; Prado, R P; Rasera, I; Oliveira, M R M; Salvadori, D M F

    2015-06-01

    Obesity is characterized by increased adipose tissue mass resulting from a chronic imbalance between energy intake and expenditure. Furthermore, there is a clearly defined relationship among fat mass expansion, chronic low-grade systemic inflammation and reactive oxygen species (ROS) generation; leading to ROS-related pathological events. In the past years, genome-wide association studies have generated convincing evidence associating genetic variation at multiple regions of the genome with traits that reflect obesity. Therefore, the present study aimed to evaluate the relationships among the gene polymorphisms ghrelin (GHRL-rs26802), ghrelin receptor (GHSR-rs572169), leptin (LEP-rs7799039), leptin receptor (LEPR-rs1137101) and fat mass and obesity-associated (FTO-rs9939609) and obesity. The relationships among these gene variants and the amount of DNA damage were also investigated. Three hundred Caucasian morbidly obese and 300 eutrophic (controls) women were recruited. In summary, the results demonstrated that the frequencies of the GHRL, GHSR, LEP and LEPR polymorphisms were not different between Brazilian white morbidly obese and eutrophic women. Exceptions were the AA-FTO genotype and allele A, which were significantly more frequent in obese women than in the controls (0.23% vs. 0.10%; 0.46 vs. 0.36, respectively), and the TT-FTO genotype and the T allele, which were less frequent in morbidly obese women (p<0.01). Furthermore, significant differences in the amount of genetic lesions associated with FTO variants were observed only in obese women. In conclusion, this study demonstrated that the analyzed SNPs were not closely associated with morbid obesity, suggesting they are not the major contributors to obesity. Therefore, our data indicated that these gene variants are not good biomarkers for predicting risk susceptibility for obesity, whereas ROS generated by the inflammatory status might be one of the causes of DNA damage in obese women, favoring

  15. Associations between polymorphisms in DNA repair genes and glioblastoma.

    PubMed

    McKean-Cowdin, Roberta; Barnholtz-Sloan, Jill; Inskip, Peter D; Ruder, Avima M; Butler, Maryann; Rajaraman, Preetha; Razavi, Pedram; Patoka, Joe; Wiencke, John K; Bondy, Melissa L; Wrensch, Margaret

    2009-04-01

    A pooled analysis was conducted to examine the association between select variants in DNA repair genes and glioblastoma multiforme, the most common and deadliest form of adult brain tumors. Genetic data for approximately 1,000 glioblastoma multiforme cases and 2,000 controls were combined from four centers in the United States that have conducted case-control studies on adult glioblastoma multiforme, including the National Cancer Institute, the National Institute for Occupational Safety and Health, the University of Texas M. D. Anderson Cancer Center, and the University of California at San Francisco. Twelve DNA repair single-nucleotide polymorphisms were selected for investigation in the pilot collaborative project. The C allele of the PARP1 rs1136410 variant was associated with a 20% reduction in risk for glioblastoma multiforme (odds ratio(CT or CC), 0.80; 95% confidence interval, 0.67-0.95). A 44% increase in risk for glioblastoma multiforme was found for individuals homozygous for the G allele of the PRKDC rs7003908 variant (odds ratio(GG), 1.44; 95% confidence interval, 1.13-1.84); there was a statistically significant trend (P = 0.009) with increasing number of G alleles. A significant, protective effect was found when three single-nucleotide polymorphisms (ERCC2 rs13181, ERCC1 rs3212986, and GLTSCR1 rs1035938) located near each other on chromosome 19 were modeled as a haplotype. The most common haplotype (AGC) was associated with a 23% reduction in risk (P = 0.03) compared with all other haplotypes combined. Few studies have reported on the associations between variants in DNA repair genes and brain tumors, and few specifically have examined their impact on glioblastoma multiforme. Our results suggest that common variation in DNA repair genes may be associated with risk for glioblastoma multiforme. PMID:19318434

  16. Serum amyloid A1: Structure, function and gene polymorphism.

    PubMed

    Sun, Lei; Ye, Richard D

    2016-05-25

    Inducible expression of serum amyloid A (SAA) is a hallmark of the acute-phase response, which is a conserved reaction of vertebrates to environmental challenges such as tissue injury, infection and surgery. Human SAA1 is encoded by one of the four SAA genes and is the best-characterized SAA protein. Initially known as a major precursor of amyloid A (AA), SAA1 has been found to play an important role in lipid metabolism and contributes to bacterial clearance, the regulation of inflammation and tumor pathogenesis. SAA1 has five polymorphic coding alleles (SAA1.1-SAA1.5) that encode distinct proteins with minor amino acid substitutions. Single nucleotide polymorphism (SNP) has been identified in both the coding and non-coding regions of human SAA1. Despite high levels of sequence homology among these variants, SAA1 polymorphisms have been reported as risk factors of cardiovascular diseases and several types of cancer. A recently solved crystal structure of SAA1.1 reveals a hexameric bundle with each of the SAA1 subunits assuming a 4-helix structure stabilized by the C-terminal tail. Analysis of the native SAA1.1 structure has led to the identification of a competing site for high-density lipoprotein (HDL) and heparin, thus providing the structural basis for a role of heparin and heparan sulfate in the conversion of SAA1 to AA. In this brief review, we compares human SAA1 with other forms of human and mouse SAAs, and discuss how structural and genetic studies of SAA1 have advanced our understanding of the physiological functions of the SAA proteins. PMID:26945629

  17. Pioglitazone stimulates AMP-activated protein kinase signalling and increases the expression of genes involved in adiponectin signalling, mitochondrial function and fat oxidation in human skeletal muscle in vivo: a randomised trial

    PubMed Central

    Sriwijitkamol, A.; Wajcberg, E.; Tantiwong, P.; Li, M.; Prentki, M.; Madiraju, M.; Jenkinson, C. P.; Cersosimo, E.; Musi, N.; DeFronzo, R. A.

    2016-01-01

    Aims/hypothesis The molecular mechanisms by which thiazolidinediones improve insulin sensitivity in type 2 diabetes are not fully understood. We hypothesised that pioglitazone would activate the adenosine 5′-monophosphate-activated protein kinase (AMPK) pathway and increase the expression of genes involved in adiponectin signalling, NEFA oxidation and mitochondrial function in human skeletal muscle. Methods A randomised, double-blind, parallel study was performed in 26 drug-naive type 2 diabetes patients treated with: (1) pioglitazone (n=14) or (2) aggressive nutritional therapy (n=12) to reduce HbA1c to levels observed in the pioglitazone-treated group. Participants were assigned randomly to treatment using a table of random numbers. Before and after 6 months, patients reported to the Clinical Research Center of the Texas Diabetes Institute for a vastus lateralis muscle biopsy followed by a 180 min euglycaemic–hyperinsulinaemic (80 mU m−2 min−1) clamp. Results All patients in the pioglitazone (n=14) or nutritional therapy (n=12) group were included in the analysis. Pioglitazone significantly increased plasma adiponectin concentration by 79% and reduced fasting plasma NEFA by 35% (both p<0.01). Following pioglitazone, insulin-stimulated glucose disposal increased by 30% (p<0.01), and muscle AMPK and acetyl-CoA carboxylase (ACC) phosphorylation increased by 38% and 53%, respectively (p<0.05). Pioglitazone increased mRNA levels for adiponectin receptor 1 and 2 genes (ADIPOR1, ADIPOR2), peroxisome proliferator-activated receptor gamma, coactivator 1 gene (PPARGC1) and multiple genes involved in mitochondrial function and fat oxidation. Despite a similar reduction in HbA1c and similar improvement in insulin sensitivity with nutritional therapy, there were no significant changes in muscle AMPK and ACC phosphorylation, or the expression of ADIPOR1, ADIPOR2, PPARGC1 and genes involved in mitochondrial function and fat oxidation. No adverse (or unexpected) effects

  18. Gene Expression and Polymorphism of Myostatin Gene and its Association with Growth Traits in Chicken.

    PubMed

    Dushyanth, K; Bhattacharya, T K; Shukla, R; Chatterjee, R N; Sitaramamma, T; Paswan, C; Guru Vishnu, P

    2016-10-01

    Myostatin is a member of TGF-β super family and is directly involved in regulation of body growth through limiting muscular growth. A study was carried out in three chicken lines to identify the polymorphism in the coding region of the myostatin gene through SSCP and DNA sequencing. A total of 12 haplotypes were observed in myostatin coding region of chicken. Significant associations between haplogroups with body weight at day 1, 14, 28, and 42 days, and carcass traits at 42 days were observed across the lines. It is concluded that the coding region of myostatin gene was polymorphic, with varied levels of expression among lines and had significant effects on growth traits. The expression of MSTN gene varied during embryonic and post hatch development stage. PMID:27565871

  19. Association between amygdala reactivity and a dopamine transporter gene polymorphism.

    PubMed

    Bergman, O; Åhs, F; Furmark, T; Appel, L; Linnman, C; Faria, V; Bani, M; Pich, E M; Bettica, P; Henningsson, S; Manuck, S B; Ferrell, R E; Nikolova, Y S; Hariri, A R; Fredrikson, M; Westberg, L; Eriksson, E

    2014-01-01

    Essential for detection of relevant external stimuli and for fear processing, the amygdala is under modulatory influence of dopamine (DA). The DA transporter (DAT) is of fundamental importance for the regulation of DA transmission by mediating reuptake inactivation of extracellular DA. This study examined if a common functional variable number tandem repeat polymorphism in the 3' untranslated region of the DAT gene (SLC6A3) influences amygdala function during the processing of aversive emotional stimuli. Amygdala reactivity was examined by comparing regional cerebral blood flow, measured with positron emission tomography and [(15)O]water, during exposure to angry and neutral faces, respectively, in a Swedish sample comprising 32 patients with social anxiety disorder and 17 healthy volunteers. In a separate US sample, comprising 85 healthy volunteers studied with blood oxygen level-dependent functional magnetic resonance imaging, amygdala reactivity was assessed by comparing the activity during exposure to threatening faces and neutral geometric shapes, respectively. In both the Swedish and the US sample, 9-repeat carriers displayed higher amygdala reactivity than 10-repeat homozygotes. The results suggest that this polymorphism contributes to individual variability in amygdala reactivity. PMID:25093598

  20. Association between amygdala reactivity and a dopamine transporter gene polymorphism

    PubMed Central

    Bergman, O; Åhs, F; Furmark, T; Appel, L; Linnman, C; Faria, V; Bani, M; Pich, E M; Bettica, P; Henningsson, S; Manuck, S B; Ferrell, R E; Nikolova, Y S; Hariri, A R; Fredrikson, M; Westberg, L; Eriksson, E

    2014-01-01

    Essential for detection of relevant external stimuli and for fear processing, the amygdala is under modulatory influence of dopamine (DA). The DA transporter (DAT) is of fundamental importance for the regulation of DA transmission by mediating reuptake inactivation of extracellular DA. This study examined if a common functional variable number tandem repeat polymorphism in the 3′ untranslated region of the DAT gene (SLC6A3) influences amygdala function during the processing of aversive emotional stimuli. Amygdala reactivity was examined by comparing regional cerebral blood flow, measured with positron emission tomography and [15O]water, during exposure to angry and neutral faces, respectively, in a Swedish sample comprising 32 patients with social anxiety disorder and 17 healthy volunteers. In a separate US sample, comprising 85 healthy volunteers studied with blood oxygen level-dependent functional magnetic resonance imaging, amygdala reactivity was assessed by comparing the activity during exposure to threatening faces and neutral geometric shapes, respectively. In both the Swedish and the US sample, 9-repeat carriers displayed higher amygdala reactivity than 10-repeat homozygotes. The results suggest that this polymorphism contributes to individual variability in amygdala reactivity. PMID:25093598

  1. Association of a transcription factor 21 gene polymorphism with hypertension

    PubMed Central

    FUJIMAKI, TETSUO; OGURI, MITSUTOSHI; HORIBE, HIDEKI; KATO, KIMIHIKO; MATSUOKA, REIKO; ABE, SHINTARO; TOKORO, FUMITAKA; ARAI, MASAZUMI; NODA, TOSHIYUKI; WATANABE, SACHIRO; YAMADA, YOSHIJI

    2015-01-01

    Various loci and genes that confer susceptibility to coronary artery disease (CAD) have been identified mainly in Caucasian populations by genome-wide association studies (GWASs). As hypertension is a major risk factor for CAD, certain polymorphisms may contribute to the genetic susceptibility to CAD through affecting the predisposition to hypertension. The aim of the present study was to examine a possible association of hypertension with 29 single-nucleotide polymorphisms (SNPs) previously identified by meta-analyses of GWASs as susceptibility loci for CAD. Study subjects comprised of 5,460 individuals (3,348 subjects with hypertension and 2,112 controls). The genotypes of SNPs were determined by the multiplex bead-based Luminex assay. The χ2 test revealed that genotype distributions and allele frequencies for rs12190287 of the transcription factor 21 gene (TCF21) and rs1122608 of the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 gene (SMARCA4) were significantly (P<0.05) associated with hypertension. Allele frequencies for rs9369640 of the phosphatase and actin regulator 1 gene (PHACTR1) and genotype distributions for rs599839 of the proline/serine-rich coiled-coil 1 gene (PSRC1) were also significantly associated with hypertension. Multivariable logistic regression analysis with adjustment for age, gender, body mass index and smoking status revealed that rs12190287 of TCF21 (P=0.0014; recessive model; odds ratio, 1.21) was significantly associated with hypertension, and the C allele represented a risk factor for this condition. Similar analyses revealed that rs1122608 of SMARCA4 (P=0.0305; dominant model; odds ratio, 0.86), rs9369640 of PHACTR1 (P=0.0119; dominant model; odds ratio, 0.82) and rs599839 of PSRC1 (P=0.0248; dominant model; odds ratio, 0.84) were also related to hypertension, with the minor T, C and G alleles, respectively, being protective against this condition. Thus, the present results

  2. Association of a transcription factor 21 gene polymorphism with hypertension.

    PubMed

    Fujimaki, Tetsuo; Oguri, Mitsutoshi; Horibe, Hideki; Kato, Kimihiko; Matsuoka, Reiko; Abe, Shintaro; Tokoro, Fumitaka; Arai, Masazumi; Noda, Toshiyuki; Watanabe, Sachiro; Yamada, Yoshiji

    2015-01-01

    Various loci and genes that confer susceptibility to coronary artery disease (CAD) have been identified mainly in Caucasian populations by genome-wide association studies (GWASs). As hypertension is a major risk factor for CAD, certain polymorphisms may contribute to the genetic susceptibility to CAD through affecting the predisposition to hypertension. The aim of the present study was to examine a possible association of hypertension with 29 single-nucleotide polymorphisms (SNPs) previously identified by meta-analyses of GWASs as susceptibility loci for CAD. Study subjects comprised of 5,460 individuals (3,348 subjects with hypertension and 2,112 controls). The genotypes of SNPs were determined by the multiplex bead-based Luminex assay. The χ(2) test revealed that genotype distributions and allele frequencies for rs12190287 of the transcription factor 21 gene (TCF21) and rs1122608 of the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 gene (SMARCA4) were significantly (P<0.05) associated with hypertension. Allele frequencies for rs9369640 of the phosphatase and actin regulator 1 gene (PHACTR1) and genotype distributions for rs599839 of the proline/serine-rich coiled-coil 1 gene (PSRC1) were also significantly associated with hypertension. Multivariable logistic regression analysis with adjustment for age, gender, body mass index and smoking status revealed that rs12190287 of TCF21 (P=0.0014; recessive model; odds ratio, 1.21) was significantly associated with hypertension, and the C allele represented a risk factor for this condition. Similar analyses revealed that rs1122608 of SMARCA4 (P=0.0305; dominant model; odds ratio, 0.86), rs9369640 of PHACTR1 (P=0.0119; dominant model; odds ratio, 0.82) and rs599839 of PSRC1 (P=0.0248; dominant model; odds ratio, 0.84) were also related to hypertension, with the minor T, C and G alleles, respectively, being protective against this condition. Thus, the present results

  3. A variety of gene polymorphisms associated with idiopathic granulomatous mastitis.

    PubMed

    Destek, Sebahattin; Gul, Vahit Onur; Ahioglu, Serkan

    2016-01-01

    Idiopathic granulomatous mastitis (IGM) is a rare and chronic inflammatory disorder. IGM mimics breast cancer regarding its clinical and radiological features. Etiology of IGM remains unclarified. Our patient was 37-year-old and 14 weeks pregnant. There was pain, redness and swelling in the right breast. The mass suggestive of malignancy was detected in sonography. Serum CA 125 and CA 15-3 levels were high. Genetic analysis was performed for the etiology. methylenetetrahydrofolate reductase (MTHFR) C 677 TT, β-fibrinogen-455 G>A, plasminogen activator inhibitor (PAI)-1 5 G/5 G, angiotensin-converting enzyme (ACE) I/D mutation was found. IGM was diagnosed by cor biopsy. An association was also reported between breast cancer and mutations in MTHFR-C 677 T, PAI-1, ACE genes. Genetic polymorphisms may involve in the development of IGM as it was seen in our case. Further studies should be conducted to better clarify this plausible association. PMID:27619324

  4. A variety of gene polymorphisms associated with idiopathic granulomatous mastitis

    PubMed Central

    Destek, Sebahattin; Gul, Vahit Onur; Ahioglu, Serkan

    2016-01-01

    Idiopathic granulomatous mastitis (IGM) is a rare and chronic inflammatory disorder. IGM mimics breast cancer regarding its clinical and radiological features. Etiology of IGM remains unclarified. Our patient was 37-year-old and 14 weeks pregnant. There was pain, redness and swelling in the right breast. The mass suggestive of malignancy was detected in sonography. Serum CA 125 and CA 15-3 levels were high. Genetic analysis was performed for the etiology. methylenetetrahydrofolate reductase (MTHFR) C 677 TT, β-fibrinogen-455 G>A, plasminogen activator inhibitor (PAI)-1 5 G/5 G, angiotensin-converting enzyme (ACE) I/D mutation was found. IGM was diagnosed by cor biopsy. An association was also reported between breast cancer and mutations in MTHFR-C 677 T, PAI-1, ACE genes. Genetic polymorphisms may involve in the development of IGM as it was seen in our case. Further studies should be conducted to better clarify this plausible association. PMID:27619324

  5. Single nucleotide polymorphisms of Kit gene in Chinese indigenous horses.

    PubMed

    Han, Haoyuan; Mao, Chunchun; Chen, Ningbo; Lan, Xianyong; Chen, Hong; Lei, Chuzhao; Dang, Ruihua

    2016-02-01

    Kit gene is a genetic determinant of horse white coat color which has been a highly valued trait in horses for at least 2,000 years. Single nucleotide polymorphisms (SNPs) in Kit are of importance due to their strong associations with melanoblast survival during embryonic development. In this study, a mutation analysis of all 21 Kit exons in 14 Chinese domestic horse breeds revealed six SNPs (g.91214T>G, g.143245T>G, g.164297C>T, g.170189C>T, g.171356C>G, and g.171471G>A), which located in 5'-UTR region, intron 6, exon 15, exon 20, intron 20, and exon 21 of the equine Kit gene, respectively. Subsequently, these six SNPs loci were genotyped in 632 Chinese horses by PCR-RFLP or direct sequencing. The six SNPs together defined 18 haplotypes, demonstrating abundant haplotype diversities in Chinese horses. All the mutant alleles and haplotypes were shared among different breeds. But fewer mutations were detected in horses from China than that from abroad, indicating that Chinese horses belong to a more ancient genetic pool. This study will provide fundamental genetic information for evaluating the genetic diversity of Kit gene in Chinese indigenous horse breeds. PMID:27348891

  6. Restriction fragment length polymorphisms associated with substance P gene

    SciTech Connect

    de Miguel, C.; Bonner, T.; Detera-Wadleigh, S.

    1987-05-01

    Substance P (SP) is an important neuropepetide detected in a variety of locations in the central nervous system. Variations in SP content or SP receptors in psychiatric disorders have been described. Using SP clones as probes the authors have found three restriction fragment length polymorphisms (RFLPs) in the SP gene. The RFLPs are generated by digestion of genomic DNA with the MspI, and RsaI and NcoI restriction endonucleases. The MspI RFLP is detected by two genomic clones mapping to the 5' end of the gene while the RsaI and NcoI rFLPs are both detected by two genomic clones on the 3' end and also by a full-length cDNA clone of the gene. All three RFLPs are characterized by two alleles. For the MspI RFLP the frequency of both alleles is similar, for the Rsa I and NcoI RFLP one of the alleles is significantly more abundant than the other. These RFLPs are now being used to determine whether any of the alleles correlate with either schizophrenia or affective disorder.

  7. KCNA5 gene polymorphism associate with idiopathic atrial fibrillation

    PubMed Central

    Tian, Li; Liu, Gang; Wang, Le; Zheng, Mingqi; Li, Yongjun

    2015-01-01

    Objective: To investigate the correlation between KCNA5 single nucleotide polymorphism (SNP) and idiopathic atrial fibrillation (IAF). Methods: A case-control study was conducted, including 282 cases of IAF patients and 300 cases of age and sex-matched normal controls; gene sequencing method was used to detect the distribution of KCNA5 SNP (rs3741930 and rs1056468) in the two groups. The IAF patients were divided into two groups based on the different genotypes of rs1056468 and rs3741930; differences in clinical parameters between the two groups of patients were compared. Results: For rs3741930, the CC, CT and TT genotype frequencies in the IAF group were 16.7%, 50.0%, and 33.3% respectively; C allele frequency in IAF group was 41.7%; in the normal control group, those were 10.0%, 49.3%, 40.7% and 34.7% respectively; CC genotype frequency and C allele frequency in IAF group were significantly higher compared with the control group (P=0.019, P=0.014). For rs1056468, the AA, AT and TT genotype frequencies in the IAF group were 44.3%, 48.6%, and 7.1% respectively; in 300 cases of normal controls, those were 38.7%, 50.7%, and 10.6% respectively; A allele frequency in IAF group was 68.6 %, and it was 64.0% in normal controls. There were no significant differences in genotype and allele frequencies between control and IAF groups (P>0.05). In IAF group, among different genotypes of rs1741930 and rs1056468, there were no significant differences in age, SBP, DBP, HR, LAD and LVEF (P>0.05). While the BMI in CC and CC+TT groups of rs3741930 locus were 26.9±2.3 Kg/m2 and 24.8±2.5 Kg/m2 respectively. There were statistical differences between the two groups (P=0.019). BMI in AA and AA+TT groups of rs1056468 locus were 24.9±2.7 Kg/m2 and 26.4±2.4 Kg/m2 respectively; There was statistically significant significance between the two groups (P=0.014). Conclusion: The single nucleotide polymorphism rs3741930 locus in KCNA5 gene was related to the risk of IAF; the population

  8. Large number of replacement polymorphisms in rapidly evolving genes of Drosophila. Implications for genome-wide surveys of DNA polymorphism.

    PubMed Central

    Schmid, K J; Nigro, L; Aquadro, C F; Tautz, D

    1999-01-01

    We present a survey of nucleotide polymorphism of three novel, rapidly evolving genes in populations of Drosophila melanogaster and D. simulans. Levels of silent polymorphism are comparable to other loci, but the number of replacement polymorphisms is higher than that in most other genes surveyed in D. melanogaster and D. simulans. Tests of neutrality fail to reject neutral evolution with one exception. This concerns a gene located in a region of high recombination rate in D. simulans and in a region of low recombination rate in D. melanogaster, due to an inversion. In the latter case it shows a very low number of polymorphisms, presumably due to selective sweeps in the region. Patterns of nucleotide polymorphism suggest that most substitutions are neutral or nearly neutral and that weak (positive and purifying) selection plays a significant role in the evolution of these genes. At all three loci, purifying selection of slightly deleterious replacement mutations appears to be more efficient in D. simulans than in D. melanogaster, presumably due to different effective population sizes. Our analysis suggests that current knowledge about genome-wide patterns of nucleotide polymorphism is far from complete with respect to the types and range of nucleotide substitutions and that further analysis of differences between local populations will be required to understand the forces more completely. We note that rapidly diverging and nearly neutrally evolving genes cannot be expected only in the genome of Drosophila, but are likely to occur in large numbers also in other organisms and that their function and evolution are little understood so far. PMID:10581279

  9. Detection of gene-anchored amplification polymorphism (GAAP) in the vicinity of plant mitochondrial genes.

    PubMed

    Loridon, K; Saumitou-Laprade, P

    2002-05-01

    A simple, semi-automatable method was established for assessing polymorphism in plant mitochondrial genome. A set of 41 mitochondrial markers based on the published Arabidopsis thaliana sequence was developed in Brassicaceae using a gene-anchored amplification polymorphism (GAAP) strategy. PCR primers were selected based on conserved coding regions of mitochondrial genes and used to amplify the corresponding 5' and/or 3' non-coding flanking regions in order to maximise sequence variability between haplotypes. The variations in fragment size were analysed on a LiCor DNA sequencer, but the methodology is compatible with various sequencing systems using denaturing polyacrylamide gels. One advantage of the method is that GAAP products can be directly sequenced (without any cloning steps) through labelled M13 consensus sequences. Mitochondrial GAAP loci gave clear and simple patterns (one or two bands) that were easy to score and highly reproducible. Nearly all mitochondrial loci examined in A. thaliana were conserved within the Brassicaceae family, and half of the primers generated products when DNA from a distant species, Beta vulgaris (Chenopodiaceae), was used as template. The GAAP markers revealed low levels of polymorphism within species but exhibited a high level of polymorphism among genera and families. Our results showed some discrepancies with respect to the published mtDNA sequence of A. thaliana. PMID:12073035

  10. Genetic polymorphisms of human UDP-glucuronosyltransferase (UGT) genes and cancer risk.

    PubMed

    Hu, Dong Gui; Mackenzie, Peter I; McKinnon, Ross A; Meech, Robyn

    2016-01-01

    Identification of genetic polymorphisms that contribute to the risk of developing cancers is important for cancer prevention. The most recent human genome GRCh38/hg38 assembly (2013) reveals thousands of genetic polymorphisms in human uridine diphosphoglucuronosyltransferase (UGT) genes. Among these, a large number of polymorphisms at the UGT1A and UGT2B genes have been shown to modulate UGT gene promoter activity or enzymatic activity. Glucuronidation plays an important role in the metabolism and clearance of endogenous and exogenous carcinogenic compounds, and this reaction is primarily catalyzed by the UGT1A and UGT2B enzymes. Therefore, it has long been hypothesized that UGT polymorphisms that reduce the capacity to glucuronidate carcinogens and other types of cancer-promoting molecules (e.g. sex hormones) are associated with an increased risk of developing cancers. A large number of case-control studies have investigated this hypothesis and these studies identified numerous UGT polymorphisms in UGT1A and UGT2B genes as genetic risk factors for a wide variety of cancers, including bladder, breast, colorectal, endometrial, esophageal, head and neck, liver, lung, prostate, and thyroid. These UGT polymorphisms may be cancer causative polymorphisms, or be linked to as yet undefined causative polymorphisms, either in UGT genes or neighboring genes. This article presents a comprehensive review of these case-control studies, discusses current areas of uncertainty, and highlights future research directions in this field. PMID:26828111

  11. Genetic Analysis of the Atrial Natriuretic Peptide Gene Polymorphisms among Essential Hypertensive Patients in Malaysia

    PubMed Central

    Ghodsian, Nooshin; Ismail, Patimah; Ahmadloo, Salma; Eskandarian, Narges; Etemad, Ali

    2016-01-01

    Background. Atrial natriuretic peptide (ANP) considerably influences blood pressure regulation through water and sodium homoeostasis. Several of the studies have utilized anonymous genetic polymorphic markers and made inconsequent claims about the ANP relevant disorders. Thus, we screened Insertion/Deletion (ID) and G191A polymorphisms of ANP to discover sequence variations with potential functional significance and to specify the linkage disequilibrium pattern between polymorphisms. The relationships of detected polymorphisms with EH with or without Type 2 Diabetes Mellitus (T2DM) status were tested subsequently. Method. ANP gene polymorphisms (I/D and A191G) were specified utilizing mutagenically separated Polymerase Chain Reaction (PCR) in 320 subjects including 163 EH case subjects and 157 controls. Result. This case-control study discovered a significant association between I/D polymorphisms of ANP gene in EH patient without T2DM. However, the study determined no association between G191A polymorphisms of ANP in EH with or without T2DM. In addition, sociodemographic factors in the case and healthy subjects exhibited strong differences (P < 0.05). Conclusion. As a risk factor, ANP gene polymorphisms may affect hypertension. Despite the small sample size in this study, it is the first research assessing the ANP gene polymorphisms in both EH and T2DM patients among Malaysian population. PMID:27413750

  12. Adiponectin and the control of female reproductive functions.

    PubMed

    Palin, Marie-France; Bordignon, V Vilceu; Murphy, Bruce D

    2012-01-01

    Adiponectin is the most abundant protein secreted by the white adipose tissue. It circulates at high levels in the bloodstream and its serum concentration is inversely correlated with body fat mass. The wide distribution of adiponectin receptors (AdipoR1, AdipoR2, and T-cadherin) in peripheral tissues and organs allows adiponectin to exert pleiotropic effects on whole-body metabolism. Besides its well-known antidiabetic, antiatherogenic, and anti-inflammatory properties, accumulating evidence suggests a direct role for adiponectin in reproductive tissues. The mammalian ovary and the ovarian follicle express AdipoR1 and AdipoR2, and treating pig granulosa cells with adiponectin induces changes characteristic of the periovulatory period. Moreover, additive effects are observed between adiponectin and insulin in induction of granulosa cell gene expression, thus suggesting that adiponectin actions on the ovary may be mediated through its insulin-sensitizing effects. Adiponectin receptors are also detected in the uterus. In women, higher AdipoR1 and AdipoR2 gene expression was observed during the mid-secretory phase of the menstrual cycle, suggesting that adiponectin is implicated in the endometrial changes in preparation for embryo implantation. Adiponectin receptors are found in oocytes and early developing pig, rabbit, and mice embryos, and it has been demonstrated that adiponectin can increase the success of porcine embryo development to the blastocyst stage in vitro. Moreover, adiponectin concentration is two to three times greater in human fetal circulation and in umbilical cord blood, compared to adult plasma. This further indicates a role for adiponectin in fetal growth. It has been further suggested that adipose-derived and locally produced adiponectin may act as a key neuromodulator of reproductive functions. For example, the inhibition of LH and GnRH release from rat pituitary and hypothalamic cells following treatment with adiponectin provides evidence that

  13. Investigation of the association between Rho/Rho-kinase gene polymorphisms and systemic sclerosis.

    PubMed

    Pehlivan, Yavuz; Yolbas, Servet; Cetin, Gozde Yıldırım; Alibaz-Oner, Fatma; Cagatay, Yonca; Yilmaz, Neslihan; Oztuzcu, Serdar; Donmez, Salim; Ozgen, Metin; Koca, Suleyman Serdar; Pamuk, Omer Nuri; Sayarlıoglu, Mehmet; Kisacik, Bunyamin; Direskeneli, Haner; Demiryurek, Abdullah Tuncay; Onat, Ahmet Mesut

    2016-03-01

    Systemic sclerosis (SSc) is a disease characterized by inflammation, vascular abnormalities and fibrosis. The role of Rho/Rho-kinase pathway was demonstrated in the pathogenesis of fibrosis, inflammation and vascular abnormalities. This study was aimed to investigate the relation between SSc and Rho/Rho-kinase gene polymorphisms. The study included 339 patients with SSc and 302 healthy subjects who were apparently healthy and at similar age and gender. Genotype distributions and allele frequencies were detected by using Chi-square test or Fisher's exact Chi-square test between groups, and the haplotype analysis was applied using online program (SHEsis). Significant association was found in a polymorphism in the ROCK1 gene (rs35996865), a polymorphism in ROCK2 gene (rs10178332), a polymorphism in RhoA gene (rs2177268) and two polymorphisms in RhoC gene (rs11102522 and rs11538960) with SSc disease (p < 0.0022). In this study, association between SSc disease and Rho/Rho-kinase gene polymorphisms was investigated for the first time; significant associations between ROCK1, ROCK2, RhoA and RhoC gene polymorphisms and SSc disease were demonstrated. The results strongly suggest that this SNP may be an important risk factor for development of SSc. However, further validation of these findings in an independent cohort is necessary. PMID:26615410

  14. Polymorphisms in DNA repair genes, smoking, and pancreatic adenocarcinoma risk.

    PubMed

    McWilliams, Robert R; Bamlet, William R; Cunningham, Julie M; Goode, Ellen L; de Andrade, Mariza; Boardman, Lisa A; Petersen, Gloria M

    2008-06-15

    Base excision repair and nucleotide excision repair are vital responses to multiple types of DNA damage, including damage from tobacco exposure. Single-nucleotide polymorphisms (SNP) in these pathways may affect DNA repair capacity and therefore influence risk for cancer development. We performed a clinic-based, case-control study comprising 481 consecutive patients with confirmed pancreatic adenocarcinoma and 625 healthy controls. Allele and genotype frequencies for 16 SNPs in DNA repair genes ERCC1, XPD/ERCC2, XPC, XPF/ERCC4, OGG1, and XRCC1 were compared after adjusting for age, sex, and smoking history. Subgroup analysis by sex and smoking history was performed. Carriers of one or two XPF/ERCC4 minor alleles at R415Q had decreased risk of pancreatic adenocarcinoma compared with those who had two major alleles [odds ratio (OR), 0.59; 95% confidence interval (95% CI), 0.40-0.85]. Heavy smokers (>40 pack-years) had increased risk for cancer if they were carriers of at least one minor allele for XPD/ERCC2 at D312N (OR, 2.78; 95% CI, 1.28-6.04) or D711D (OR, 2.19; 95% CI, 1.01-4.73). No other significant differences in risk were identified. Minor alleles in DNA repair genes XPF/ERCC4 and XPD/ERCC2 were associated with altered risk for pancreatic cancer. PMID:18544627

  15. Polymorphisms in mucin genes in the development of gastric cancer

    PubMed Central

    Wen, Rong; Gao, Fang; Zhou, Cheng-Jiang; Jia, Yan-Bin

    2015-01-01

    Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. In areas of high prevalence, such as Japan, South Korea and China, most cases of GC are related to Helicobacter pylori (H. pylori), which involves well-characterized sequential stages, including infection, atrophic gastritis, intestinal metaplasia, dysplasia, and GC. Mucins are the most abundant high-molecular-weight glycoproteins in mucus, which is the first line of defense and plays a major role in blocking pathogenic factors. Normal gastric mucosa shows expression of MUC1, MUC5AC and MUC6 that is specific to cell type. However, the specific pattern of MUC1, MUC5AC and MUC6 expression is changed in gastric carcinogenesis, accompanied by de novo expression of secreted MUC2. Recent studies have provided evidence that variations in these mucin genes affect many steps of GC development, such as H. pylori infection, and gastric precancerous lesions. In this review, we focus on studies of the association between polymorphisms in mucin genes and development of GC. This information should be helpful for the early detection, surveillance, and treatment of GC. PMID:26600932

  16. KIR genes polymorphism in Argentinean Caucasoid and Amerindian populations.

    PubMed

    Flores, A C; Marcos, C Y; Paladino, N; Capucchio, M; Theiler, G; Arruvito, L; Pardo, R; Habegger, A; Williams, F; Middleton, D; Fainboim, L

    2007-06-01

    In natural killer cells, killer immunoglobulin-like receptors (KIRs) loci code for either inhibitory or activating receptors, and according to the number of genes present in each individual, it is possible to identify a high rate of polymorphism in the populations. We performed KIR typing by polymerase chain reaction-sequence-specific oligonucleotide probing in 402 Argentinean Caucasoid and in two Amerindian populations (101 Wichis and 54 Chiriguanos) from the North of Argentina. KIR2DL4, KIR3DL2, KIR3DL3 and KIR3DP1 were always present, whereas the frequencies of KIR2DL1, KIR2DL3, KIR2DS4, KIR3DL1 and KIR2DP1 ranged between 84% and 96%. The frequencies of KIR2DS2, KIR2DL2, KIR2DL5, KIR2DS5, KIR2DS1 and KIR3DS1 ranged between 41% and 62%. The KIR2DS3 with a frequency of 29% in Argentinean Caucasoid population was present at a very low frequency in Amerindian populations. Haplotype segregation studies performed in 10 Wichi families showed the presence of only three haplotypes: A, B5 and B1. The Amerindian populations showed several similarities to Asian but not to Caucasoid populations with regard to the frequency of KIR2DS3, full-length KIR2DS4 gene and KIR2DL4 alleles. PMID:17498266

  17. Serotyping of Streptococcus pneumoniae Based on Capsular Genes Polymorphisms

    PubMed Central

    Raymond, Frédéric; Boucher, Nancy; Allary, Robin; Robitaille, Lynda; Lefebvre, Brigitte; Tremblay, Cécile

    2013-01-01

    Streptococcus pneumoniae serotype epidemiology is essential since serotype replacement is a concern when introducing new polysaccharide-conjugate vaccines. A novel PCR-based automated microarray assay was developed to assist in the tracking of the serotypes. Autolysin, pneumolysin and eight genes located in the capsular operon were amplified using multiplex PCR. This step was followed by a tagged fluorescent primer extension step targeting serotype-specific polymorphisms. The tagged primers were then hybridized to a microarray. Results were exported to an expert system to identify capsular serotypes. The assay was validated on 166 cultured S. pneumoniae samples from 63 different serotypes as determined by the Quellung method. We show that typing only 12 polymorphisms located in the capsular operon allows the identification at the serotype level of 22 serotypes and the assignation of 24 other serotypes to a subgroup of serotypes. Overall, 126 samples (75.9%) were correctly serotyped, 14 were assigned to a member of the same serogroup, 8 rare serotypes were erroneously serotyped, and 18 gave negative serotyping results. Most of the discrepancies involved rare serotypes or serotypes that are difficult to discriminate using a DNA-based approach, for example 6A and 6B. The assay was also tested on clinical specimens including 43 cerebrospinal fluid samples from patients with meningitis and 59 nasopharyngeal aspirates from bacterial pneumonia patients. Overall, 89% of specimens positive for pneumolysin were serotyped, demonstrating that this method does not require culture to serotype clinical specimens. The assay showed no cross-reactivity for 24 relevant bacterial species found in these types of samples. The limit of detection for serotyping and S. pneumoniae detection was 100 genome equivalent per reaction. This automated assay is amenable to clinical testing and does not require any culturing of the samples. The assay will be useful for the evaluation of serotype

  18. The Evaluation of IL6 and ESR1 Gene Polymorphisms in Primary Dysmenorrhea.

    PubMed

    Ozsoy, Asker Zeki; Karakus, Nevin; Yigit, Serbulent; Cakmak, Bulent; Nacar, Mehmet Can; Yılmaz Dogru, Hatice

    2016-01-01

    Primary dysmenorrhea is the most common gynecological complaint with painful menstrual cramps in pelvis without any pathology. It affects about half of menstruating women, and it causes significant disruption in quality of life. We investigated the association between IL6 gene promoter and ESR1 gene XbaI and PvuII polymorphisms and primary dysmenorrhea. In this case-control study, 152 unrelated young women with primary dysmenorrhea and 150 unrelated healthy age-matched controls participated. Genomic DNA was isolated and IL6 and ESR1 gene polymorphisms were genotyped using PCR-based RFLP assay. The distribution of genotype and allele frequencies of IL6 gene promoter and ESR1 gene XbaI polymorphisms were not statistically different between patients and controls (p > 0.05). However, the genotype and allele frequencies of ESR1 gene PvuII polymorphism showed statistically significant differences between primary dysmenorrhea patients and controls (p = 0.009 and p = 0.021, respectively). Statistically significant associations were also observed between age and married status of primary dysmenorrhea patients and ESR1 gene PvuII polymorphism (p = 0.044 and p = 0.023, respectively). In combined genotype analyses, AG at ESR1 XbaI and TC at ESR1 PvuII loci encoded a p-value of 0.027. Thus, individuals who are heterozygote at both loci have a lower risk of developing primary dysmenorrhea. Our study suggests no strong association between IL6 gene promoter and ESR1 gene XbaI polymorphisms and primary dysmenorrhea in Turkish women. However, ESR1 gene PvuII polymorphism showed statistically significant differences between primary dysmenorrhea patients and controls. The potential association between ESR1 gene PvuII polymorphism and age and married status of dysmenorrhea patients deserves further consideration. PMID:26700208

  19. Genetic mapping of the human tryptophan hydroxylase gene on chromosome 11, using an intronic conformational polymorphism

    SciTech Connect

    Nielsen, D.A.; Goldman, D. ); Dean, M. )

    1992-12-01

    The identification of polymorphic alleles at loci coding for functional genes is crucial for genetic association and linkage studies. Since the tryptophan hydroxylase (TPH) gene codes for the rate-limiting enzyme in the biosynthesis of the neurotransmitter serotonin, it would be advantageous to identify a polymorphism in this gene. By examining introns of the human TPH gene by PCR amplification and analysis by the single-strand conformation polymorphism (SSCP) technique, an SSCP was revealed with two alleles that occur with frequencies of .40 and .60 in unrelated Caucasians. DNAs from 24 informative CEPH families were typed for the TPH intron polymorphism and analyzed with respect to 10 linked markers on chromosome 11, between p13 and p15, with the result that TPH was placed between D11S151 and D11S134. This region contains loci for several important genes, including those for Beckwith-Wiedemann syndrome and tyrosine hydroxylase. 37 refs., 2 figs., 1 tab.

  20. Polymorphisms of nucleotide excision repair genes predict melanoma survival.

    PubMed

    Li, Chunying; Yin, Ming; Wang, Li-E; Amos, Christopher I; Zhu, Dakai; Lee, Jeffrey E; Gershenwald, Jeffrey E; Grimm, Elizabeth A; Wei, Qingyi

    2013-07-01

    Melanoma is the most highly malignant skin cancer, and nucleotide excision repair (NER) is involved in melanoma susceptibility. In this analysis of 1,042 melanoma patients, we evaluated whether genetic variants of NER genes may predict survival outcome of melanoma patients. We used genotyping data of 74 tagging single-nucleotide polymorphisms (tagSNPs) in eight core NER genes from our genome-wide association study (including two in XPA, 14 in XPC, three in XPE, four in ERCC1, 10 in ERCC2, eight in ERCC3, 14 in ERCC4, and 19 in ERCC5) and evaluated their associations with prognosis of melanoma patients. Using the Cox proportional hazards model and Kaplan-Meier analysis, we found a predictive role of XPE rs28720291, ERCC5 rs4150314, XPC rs2470458, and ERCC2 rs50871 SNPs in the prognosis of melanoma patients (rs28720291: AG vs. GG, adjusted hazard ratio (adjHR)=11.2, 95% confidence interval (CI) 3.04-40.9, P=0.0003; rs4150314: AG vs. GG, adjHR=4.76, 95% CI 1.09-20.8, P=0.038; rs2470458: AA vs. AG/GG, adjHR=2.11, 95% CI 1.03-4.33, P=0.040; and rs50871: AA vs. AC/CC adjHR=2.27, 95% CI 1.18-4.35, P=0.015). Patients with an increasing number of unfavorable genotypes had markedly increased death risk. Genetic variants of NER genes, particularly XPE rs28720291, ERCC5 rs4150314, XPC rs2470458, and ERCC2 rs50871, may independently or jointly modulate survival outcome of melanoma patients. Because our results were based on a median follow-up of 3 years without multiple test corrections, additional large prospective studies are needed to confirm our findings. PMID:23407396

  1. Olfactory Receptor Gene Polymorphisms and Nonallergic Vasomotor Rhinitis

    PubMed Central

    Bernstein, Jonathan A.; Zhang, Ge; Jin, Li; Abbott, Carol; Nebert, Daniel W.

    2009-01-01

    We sought a genotype-phenotype association: between single-nucleotide polymorphisms (SNPs) in olfactory receptor (OR) genes from the two largest OR gene clusters and odor-triggered nonallergic vasomotor rhinitis (nVMR). In the initial pedigree screen, using transmission disequilibrium test (TDT) analysis, six SNPs showed “significant” p-values between 0.0449 and 0.0043. In a second case-control population, the previously identified six SNPs did not re-emerge, whereas four new SNPs showed p-values between 0.0490 and 0.0001. Combining both studies, none of the SNPs in the TDT analysis survived the Bonferroni correction. In the population study, one SNP showed an empirical p-value of 0.0066 by shuffling cases and controls with 105 replicates; however, the p-value for this SNP was 0.83 in the pedigree study. This study emphasizes that underpowered studies having p-values between <0.05 and 0.0001 should be regarded as inconclusive and require further replication before concluding the study is “informative.” However, we believe that our hypothesis that an association between OR genotypes and the nVMR phenotype remains feasible. Future studies using either a genomewide association study of all OR gene-pseudogene regions throughout the genome—at the current recommended density of 2.5 to 5 kb per tag SNP—or studies incorporating microarray analyses of the entire “OR genome” in well-characterized nVMR patients are required. PMID:18446592

  2. Detection of prion gene promoter and intron1 indel polymorphisms in Anatolian water buffalo (Bubalus bubalis).

    PubMed

    Oztabak, K; Ozkan, E; Soysal, I; Paya, I; Un, C

    2009-12-01

    Bovine spongiform encephalopathy (BSE) is a fatal disease caused by miss folded prion protein. Studies in the cattle, comparing genetic data from BSE diseased and healthy animals have shown that indel polymorphisms in the promoter and intron 1 of PRNP gene were associated with disease susceptibility. Several studies were conducted to find out allele and genotypic frequencies of indel polymorphisms in promoter and intron 1 of the cattle PRNP gene. Unlike domestic cattle and bison, no indel polymorphisms of the PRNP promoter and intron 1 were examined in any population of the water buffalo (Bubalus bubalis). Aim of this study was to analyse frequencies of allele, genotype, and haplotype of the indel polymorphisms (23 bp indel in promoter and 12 bp indel in intron 1) in prion protein coding gene (PRNP) of water buffalo. Therefore a PCR based procedure, previously used in cattle to detect indel polymorphisms of PRNP promoter and intron 1 locus, was applied to 106 Anatolian water buffalo DNAs. Our results have revealed high frequency of in variants and in23/in12 haplotype for PRNP promoter and intron 1 indel polymorphisms in water buffalo. The results of the study have demonstrated that frequencies of allele, genotype, and haplotype of the indel polymorphisms in PRNP gene of the Anatolian water buffalo are significantly different those from cattle and bison PRNP indel polymorphisms. PMID:19912420

  3. APOLIPOPROTEIN E GENE POLYMORPHISMS ARE NOT ASSOCIATED WITH DIABETIC RETINOPATHY: THE ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    PURPOSE: Polymorphism of the apolipoprotein E (APOE) gene has been associated with dyslipidemia and cardiovascular disease. This study examines the association of APOE polymorphisms and diabetic retinopathy. DESIGN: Population-based cross-sectional study. METHODS: We studied 1,398 people aged 49 to ...

  4. Polymorphisms in Dopamine System Genes Are Associated with Individual Differences in Attention in Infancy

    ERIC Educational Resources Information Center

    Holmboe, Karla; Nemoda, Zsofia; Fearon, R. M. Pasco; Csibra, Gergely; Sasvari-Szekely, Maria; Johnson, Mark H.

    2010-01-01

    Knowledge about the functional status of the frontal cortex in infancy is limited. This study investigated the effects of polymorphisms in four dopamine system genes on performance in a task developed to assess such functioning, the Freeze-Frame task, at 9 months of age. Polymorphisms in the catechol-O-methyltransferase ("COMT") and the dopamine…

  5. Adiponectin in mice with altered GH action: links to insulin sensitivity and longevity?

    PubMed

    Lubbers, Ellen R; List, Edward O; Jara, Adam; Sackman-Sala, Lucila; Cordoba-Chacon, Jose; Gahete, Manuel D; Kineman, Rhonda D; Boparai, Ravneet; Bartke, Andrzej; Kopchick, John J; Berryman, Darlene E

    2013-03-01

    Adiponectin is positively correlated with longevity and negatively correlated with many obesity-related diseases. While there are several circulating forms of adiponectin, the high-molecular-weight (HMW) version has been suggested to have the predominant bioactivity. Adiponectin gene expression and cognate serum protein levels are of particular interest in mice with altered GH signaling as these mice exhibit extremes in obesity that are positively associated with insulin sensitivity and lifespan as opposed to the typical negative association of these factors. While a few studies have reported total adiponectin levels in young adult mice with altered GH signaling, much remains unresolved, including changes in adiponectin levels with advancing age, proportion of total adiponectin in the HMW form, adipose depot of origin, and differential effects of GH vs IGF1. Therefore, the purpose of this study was to address these issues using assorted mouse lines with altered GH signaling. Our results show that adiponectin is generally negatively associated with GH activity, regardless of age. Further, the amount of HMW adiponectin is consistently linked with the level of total adiponectin and not necessarily with previously reported lifespan or insulin sensitivity of these mice. Interestingly, circulating adiponectin levels correlated strongly with inguinal fat mass, implying that the effects of GH on adiponectin are depot specific. Interestingly, rbGH, but not IGF1, decreased circulating total and HMW adiponectin levels. Taken together, these results fill important gaps in the literature related to GH and adiponectin and question the frequently reported associations of total and HMW adiponectin with insulin sensitivity and longevity. PMID:23261955

  6. Single nucleotide polymorphism in transcriptional regulatory regions and expression of environmentally responsive genes

    SciTech Connect

    Wang, Xuting; Tomso, Daniel J.; Liu Xuemei; Bell, Douglas A. . E-mail: BELL1@niehs.nih.gov

    2005-09-01

    Single nucleotide polymorphisms (SNPs) in the human genome are DNA sequence variations that can alter an individual's response to environmental exposure. SNPs in gene coding regions can lead to changes in the biological properties of the encoded protein. In contrast, SNPs in non-coding gene regulatory regions may affect gene expression levels in an allele-specific manner, and these functional polymorphisms represent an important but relatively unexplored class of genetic variation. The main challenge in analyzing these SNPs is a lack of robust computational and experimental methods. Here, we first outline mechanisms by which genetic variation can impact gene regulation, and review recent findings in this area; then, we describe a methodology for bioinformatic discovery and functional analysis of regulatory SNPs in cis-regulatory regions using the assembled human genome sequence and databases on sequence polymorphism and gene expression. Our method integrates SNP and gene databases and uses a set of computer programs that allow us to: (1) select SNPs, from among the >9 million human SNPs in the NCBI dbSNP database, that are similar to cis-regulatory element (RE) consensus sequences; (2) map the selected dbSNP entries to the human genome assembly in order to identify polymorphic REs near gene start sites; (3) prioritize the candidate polymorphic RE containing genes by searching the existing genotype and gene expression data sets. The applicability of this system has been demonstrated through studies on p53 responsive elements and is being extended to additional pathways and environmentally responsive genes.

  7. Copy number polymorphisms are not a common feature of innate immune genes.

    PubMed

    Linzmeier, Rose M; Ganz, Tomas

    2006-07-01

    Extensive copy number polymorphism was recently reported for innate immunity-related alpha-defensin genes DEFA1 and DEFA3 and beta-defensin genes DEFB4, DEFB103, and DEFB104. To establish whether such polymorphisms are a common feature of innate immune genes we used quantitative real-time PCR to determine the copy numbers of seven genes whose products have important innate immune functions. The genes encoding lysozyme, lactoferrin, cathelicidin antimicrobial peptide (hCAP18/LL-37), cathepsin G, bactericidal/permeability-increasing protein, azurocidin (CAP37/heparin-binding protein), and neutrophil elastase were each found to be single copy per haploid genome. These findings, along with the recent observation that defensin genes DEFA4, DEFA5, DEFA6, and DEFB1 are single copy, suggest that copy number polymorphisms are not a common feature of the innate immune genome but are restricted to a small subset of innate immunity-related genes. PMID:16617005

  8. Association of ACE Gene I/D polymorphism with migraine in Kashmiri population

    PubMed Central

    Wani, Irfan Yousuf; Sheikh, Saleem; Shah, Zafar Amin; Pandith, Arshid A.; Wani, Mushtaq; Asimi, Ravouf; Wani, Maqbool; Sheikh, Shahnawaz; Mehraj, Iqra

    2016-01-01

    Introduction: Migraine is a complex, recurrent headache disorder that is one of the most common complaints in neurology practice. The role of various genes in its pathogenesis is being studied. We did this study to see whether an association exists between ACE gene I/D polymorphism and migraine in our region. Materials and Methods: The study included 100 patients diagnosed with migraine and 121 healthy controls. The study subject were age and gender matched. The analysis was based on Polymerase Chain Reaction (PCR) and included following steps: DNA extraction from blood, PCR and Restriction Fragment Length Polymorphism (RFLP). Results: Out of 100 cases, 69 were females and 31 were males. Fifty-seven were having migraine without aura and 43 had migraine with aura. 45 of the cases had II polymorphism, 40 had ID polymorphism and 15 had DD polymorphism in ACE gene. Conclusion: We were not able to find a statistically significant association between ACE gene I/D polymorphism with migraine. The reason for difference in results between our study and other studies could be because of different ethnicity in study populations. So a continuous research is needed in this regard in order to find the genes and different polymorphism that increase the susceptibility of Kashmiri population to migraine. PMID:27011636

  9. Role of Adiponectin in Coronary Heart Disease Risk

    PubMed Central

    Lawlor, Debbie A.; de Oliveira, Cesar; White, Jon; Horta, Bernardo Lessa; Barros, Aluísio J.D.

    2016-01-01

    Rationale: Hypoadiponectinemia correlates with several coronary heart disease (CHD) risk factors. However, it is unknown whether adiponectin is causally implicated in CHD pathogenesis. Objective: We aimed to investigate the causal effect of adiponectin on CHD risk. Methods and Results: We undertook a Mendelian randomization study using data from genome-wide association studies consortia. We used the ADIPOGen consortium to identify genetic variants that could be used as instrumental variables for the effect of adiponectin. Data on the association of these genetic variants with CHD risk were obtained from CARDIoGRAM (22 233 CHD cases and 64 762 controls of European ancestry) and from CARDIoGRAMplusC4D Metabochip (63 746 cases and 130 681 controls; ≈ 91% of European ancestry) consortia. Data on the association of genetic variants with adiponectin levels and with CHD were combined to estimate the influence of blood adiponectin on CHD risk. In the conservative approach (restricted to using variants within the adiponectin gene as instrumental variables), each 1 U increase in log blood adiponectin concentration was associated with an odds ratio for CHD of 0.83 (95% confidence interval, 0.68–1.01) in CARDIoGRAM and 0.97 (95% confidence interval, 0.84–1.12) in CARDIoGRAMplusC4D Metabochip. Findings from the liberal approach (including variants in any locus across the genome) indicated a protective effect of adiponectin that was attenuated to the null after adjustment for known CHD predictors. Conclusions: Overall, our findings do not support a causal role of adiponectin levels in CHD pathogenesis. PMID:27252388

  10. Adiponectin Reduces Hepatic Stellate Cell Migration by Promoting Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) Secretion*

    PubMed Central

    Ramezani-Moghadam, Mehdi; Wang, Jianhua; Ho, Vikki; Iseli, Tristan J.; Alzahrani, Badr; Xu, Aimin; Van der Poorten, David; Qiao, Liang; George, Jacob; Hebbard, Lionel

    2015-01-01

    Hepatic stellate cells (HSC) are central players in liver fibrosis that when activated, proliferate, migrate to sites of liver injury, and secrete extracellular matrix. Obesity, a known risk factor for liver fibrosis is associated with reduced levels of adiponectin, a protein that inhibits liver fibrosis in vivo and limits HSC proliferation and migration in vitro. Adiponectin-mediated activation of adenosine monophosphate-activated kinase (AMPK) inhibits HSC proliferation, but the mechanism by which it limits HSC migration to sites of injury is unknown. Here we sought to elucidate how adiponectin regulates HSC motility. Primary rat HSCs were isolated and treated with adiponectin in migration assays. The in vivo actions of adiponectin were examined by treating mice with carbon tetrachloride for 12 weeks and then injecting them with adiponectin. Cell and tissue samples were collected and analyzed for gene expression, signaling, and histology. Serum from patients with liver fibrosis was examined for adiponectin and tissue inhibitor of metalloproteinase-1 (TIMP-1) protein. Adiponectin administration into mice increased TIMP-1 gene and protein expression. In cultured HSCs, adiponectin promoted TIMP-1 expression and through binding of TIMP-1 to the CD63/β1-integrin complex reduced phosphorylation of focal adhesion kinase to limit HSC migration. In mice with liver fibrosis, adiponectin had similar effects and limited focal adhesion kinase phosphorylation. Finally, in patients with advanced fibrosis, there was a positive correlation between serum adiponectin and TIMP-1 levels. In sum, these data show that adiponectin stimulates TIMP-1 secretion by HSCs to retard their migration and contributes to the anti-fibrotic effects of adiponectin. PMID:25575598

  11. Androgen Receptor Gene Polymorphism, Aggression, and Reproduction in Tanzanian Foragers and Pastoralists

    PubMed Central

    Butovskaya, Marina L.; Lazebny, Oleg E.; Vasilyev, Vasiliy A.; Dronova, Daria A.; Karelin, Dmitri V.; Mabulla, Audax Z. P.; Shibalev, Dmitri V.; Shackelford, Todd K.; Fink, Bernhard; Ryskov, Alexey P.

    2015-01-01

    The androgen receptor (AR) gene polymorphism in humans is linked to aggression and may also be linked to reproduction. Here we report associations between AR gene polymorphism and aggression and reproduction in two small-scale societies in northern Tanzania (Africa)—the Hadza (monogamous foragers) and the Datoga (polygynous pastoralists). We secured self-reports of aggression and assessed genetic polymorphism of the number of CAG repeats for the AR gene for 210 Hadza men and 229 Datoga men (aged 17–70 years). We conducted structural equation modeling to identify links between AR gene polymorphism, aggression, and number of children born, and included age and ethnicity as covariates. Fewer AR CAG repeats predicted greater aggression, and Datoga men reported more aggression than did Hadza men. In addition, aggression mediated the identified negative relationship between CAG repeats and number of children born. PMID:26291982

  12. Tumour necrosis factor-alpha gene polymorphisms and Alzheimer's disease.

    PubMed

    Culpan, Doris; MacGowan, Sian H; Ford, Julia M; Nicoll, James A R; Griffin, W Sue; Dewar, Deborah; Cairns, Nigel J; Hughes, Anthony; Kehoe, Patrick G; Wilcock, Gordon K

    2003-10-16

    Recent findings suggest that production of pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha), is increased in the brains of people with Alzheimer's disease (AD). We used direct sequencing methods on a section of the enhancer/promoter region and on a smaller fragment located 10.5 kb upstream of the TNF-alpha gene to respectively examine TNF-alpha polymorphisms and TNF-a and -b microsatellite alleles in a cohort of 235 post-mortem confirmed AD and 130 control cases. None of the TNF-alpha point mutations or microsatellite alleles investigated proved to be independent risk factors for AD. However, when -308/A, -238/G and TNF-a2 were examined as a 2-1-2 haplotype, we observed that the absence of that haplotype was significantly associated with AD (P = 0.014, Fisher's exact test) suggesting that the 2-1-2 haplotype may be protective against AD. PMID:12962917

  13. The prion-related protein (testis-specific) gene (PRNT) is highly polymorphic in Portuguese sheep.

    PubMed

    Mesquita, P; Garcia, V; Marques, M R; Santos Silva, F; Oliveira Sousa, M C; Carolino, I; Pimenta, J; Fontes, C M G A; Horta, A E M; Prates, J A M; Pereira, R M

    2016-02-01

    The objective of this study was to search for polymorphisms in the ovine prion-related protein (testis-specific) gene (PRNT). Sampling included 567 sheep from eight Portuguese breeds. The PRNT gene-coding region was analyzed by single-strand conformation polymorphism and sequencing, allowing the identification of the first ovine PRNT polymorphisms, in codons 6, 38, 43 and 48: c.17C>T (p.Ser6Phe, which disrupts a consensus arginine-X-X-serine/threonine motif); c.112G>C (p.Gly38>Arg); c.129T>C and c.144A>G (synonymous) respectively. Polymorphisms in codons 6, 38 and 48 occur simultaneously in 50.6% of the animals, 38.8% presenting as heterozygous. To study the distribution of the polymorphism in codon 43, a restriction fragment length polymorphism analysis was performed. Polymorphic variant c.129C, identified in 89.8% of the animals with 32.8% presented as heterozygous, was considered the wild genotype in Portuguese sheep. Eight different haplotypes which have comparable distribution in all breeds were identified for the PRNT gene. In conclusion, the PRNT coding region is highly polymorphic in sheep, unlike the prion protein 2 dublet gene (PRND), in which we previously found only one synonymous substitution (c.78G>A), in codon 26. The absence or reduced number of PRND heterozygotes (c.78G>A) was significantly associated with three PRNT haplotypes (17C-112G-129T-144A,17CT-112GC-129CT-144AG and 17T-112C-129C-144G), and the only three animals found homozygous at c.78A had the 17C-112G-129C-144A PRNT haplotype. These results constitute evidence of an association between polymorphic variation in PRND and PRNT genes, as has already been observed for PRND and prion protein gene (PRNP). PMID:26538093

  14. Association of Single Nucleotide Polymorphisms in the CAST Gene Associated with Longissimus Tenderness in Beef Cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective was to assess the association of single nucleotide polymorphisms (SNP) developed on the CAST gene, with longissimus tenderness. Forty one SNP were identified in the CAST gene and assays were developed. Markers were scattered throughout the gene. These markers, in conjunction with a com...

  15. Association of single nucleotide polymorphisms in candidate genes residing under quantitative trait loci in beef cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective was to assess the association of single nucleotide polymorphisms (SNP) developed on candidate genes residing under previously identified quantitative trait loci for marbling score and meat tenderness. Two hundred five SNP were identified on twenty candidate genes. Genes selected under ...

  16. Effect of transporter and DNA repair gene polymorphisms to lung cancer chemotherapy toxicity.

    PubMed

    Chen, Juan; Wu, Lin; Wang, Ying; Yin, Jiye; Li, Xiangping; Wang, Zhan; Li, Huihua; Zou, Ting; Qian, Chenyue; Li, Chuntian; Zhang, Wei; Zhou, Honghao; Liu, Zhaoqian

    2016-02-01

    Lung cancer is the first leading cause of cancer deaths. Chemotherapy toxicity is one of factors that limited the efficacy of platinum-based chemotherapy in lung cancer patients. Transporters and DNA repair genes play critical roles in occurrence of platinum-based chemotherapy toxicity. To investigate the relationships between transporter and DNA repair gene polymorphisms and platinum-based chemotherapy toxicity in lung cancer patients, we selected 60 polymorphisms in 14 transporters and DNA repair genes. The polymorphisms were genotyped in 317 lung cancer patients by Sequenom MassARRAY. Logistic regression was performed to estimate the association of toxicity outcome with the polymorphisms by PLINK. Our results showed that polymorphisms of SLC2A1 (rs3738514, rs4658, rs841844) were significantly related to overall toxicity. XRCC5 (rs1051685, rs6941) and AQP2 (10875989, rs3759125) polymorphisms were associated with hematologic toxicity. AQP2 polymorphisms (rs461872, rs7305534) were correlated with gastrointestinal toxicity. In conclusion, genotypes of these genes may be used to predict the platinum-based chemotherapy toxicity in lung cancer patients. PMID:26358256

  17. Innate immunity gene polymorphisms and the risk of colorectal neoplasia.

    PubMed

    Chang, Cindy M; Chia, Victoria M; Gunter, Marc J; Zanetti, Krista A; Ryan, Bríd M; Goodman, Julie E; Harris, Curtis C; Weissfeld, Joel; Huang, Wen-Yi; Chanock, Stephen; Yeager, Meredith; Hayes, Richard B; Berndt, Sonja I

    2013-11-01

    Inherited variation in genes that regulate innate immunity and inflammation may contribute to colorectal neoplasia risk. To evaluate this association, we conducted a nested case-control study of 451 colorectal cancer cases, 694 colorectal advanced adenoma cases and 696 controls of European descent within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. A total of 935 tag single-nucleotide polymorphisms (SNPs) in 98 genes were evaluated. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association with colorectal neoplasia. Sixteen SNPs were associated with colorectal neoplasia risk at P < 0.01, but after adjustment for multiple testing, only rs2838732 (ITGB2) remained suggestively associated with colorectal neoplasia (OR(per T allele) = 0.68, 95% CI: 0.57-0.83, P = 7.7 × 10(-5), adjusted P = 0.07). ITGB2 codes for the CD18 protein in the integrin beta chain family. The ITGB2 association was stronger for colorectal cancer (OR(per T allele) = 0.41, 95% CI: 0.30-0.55, P = 2.4 × 10(-) (9)) than for adenoma (OR(per T allele) = 0.84, 95%CI: 0.69-1.03, P = 0.08), but it did not replicate in the validation study. The ITGB2 rs2838732 association was significantly modified by smoking status (P value for interaction = 0.003). Among never and former smokers, it was inversely associated with colorectal neoplasia (OR(per T allele) = 0.5, 95% CI: 0.37-0.69 and OR(per T allele) = 0.72, 95% CI: 0.54-0.95, respectively), but no association was seen among current smokers. Other notable findings were observed for SNPs in BPI/LBP and MYD88. Although the results need to be replicated, our findings suggest that genetic variation in inflammation-related genes may be related to the risk of colorectal neoplasia. PMID:23803696

  18. Innate immunity gene polymorphisms and the risk of colorectal neoplasia

    PubMed Central

    Berndt, Sonja I.

    2013-01-01

    Inherited variation in genes that regulate innate immunity and inflammation may contribute to colorectal neoplasia risk. To evaluate this association, we conducted a nested case–control study of 451 colorectal cancer cases, 694 colorectal advanced adenoma cases and 696 controls of European descent within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. A total of 935 tag single-nucleotide polymorphisms (SNPs) in 98 genes were evaluated. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association with colorectal neoplasia. Sixteen SNPs were associated with colorectal neoplasia risk at P < 0.01, but after adjustment for multiple testing, only rs2838732 (ITGB2) remained suggestively associated with colorectal neoplasia (ORper T allele = 0.68, 95% CI: 0.57–0.83, P = 7.7 × 10–5, adjusted P = 0.07). ITGB2 codes for the CD18 protein in the integrin beta chain family. The ITGB2 association was stronger for colorectal cancer (ORper T allele = 0.41, 95% CI: 0.30–0.55, P = 2.4 × 10− 9) than for adenoma (ORper T allele = 0.84, 95%CI: 0.69–1.03, P = 0.08), but it did not replicate in the validation study. The ITGB2 rs2838732 association was significantly modified by smoking status (P value for interaction = 0.003). Among never and former smokers, it was inversely associated with colorectal neoplasia (ORper T allele = 0.5, 95% CI: 0.37–0.69 and ORper T allele = 0.72, 95% CI: 0.54–0.95, respectively), but no association was seen among current smokers. Other notable findings were observed for SNPs in BPI/LBP and MYD88. Although the results need to be replicated, our findings suggest that genetic variation in inflammation-related genes may be related to the risk of colorectal neoplasia. PMID:23803696

  19. Vitamin D receptor gene polymorphisms and the risk for female reproductive cancers: A meta-analysis.

    PubMed

    Mun, Myung-Jin; Kim, Tae-Hee; Hwang, Ji-Young; Jang, Won-Cheoul

    2015-06-01

    Vitamin D receptor (VDR) gene polymorphisms and the risks for various breast and ovarian cancers have been reported in many epidemiological studies. However, the associations between VDR gene polymorphisms and the risk for each type of cancer are unclear. The aim of this meta-analysis was to evaluate the associations between VDR gene polymorphisms and female reproductive cancers. A systematic review was performed with the PubMed Science Direct, Scopus, and Google Scholar databases up to April 2014 using the search terms "vitamin D receptor or VDR" and "variant or polymorphism or SNP" with terms for breast, ovarian, cervical, endometrial, uterine, and vaginal cancers. A meta-analysis with the pooled odds ratios and 95% confidence intervals was carried out to assess the associations between VDR polymorphisms (Cdx-2, FokI, BsmI, ApaI, and TaqI) and the risks for reproductive cancers under the heterozygous, homozygous, dominant, and recessive models with fixed or random effects models. Six ovarian cancer studies (13 individual studies involving 4107 cases and 6661 controls) and 29 breast cancer studies (38 individual studies involving 16,453 cases and 22,044 controls) were included in our meta-analysis. Our results indicate that the FokI polymorphism was related to increased risks for breast and ovarian cancers, whereas the BsmI polymorphism was associated with a decreased risk for developing these cancers. Our comprehensive meta-analysis indicated that the FokI and BsmI VDR gene polymorphisms may be significantly associated with gynecological cancers. We suggest monitoring VDR gene polymorphisms as potential biomarkers in patients with gynecological malignancy. PMID:25882760

  20. Osteoporosis and polymorphisms of osteoprotegerin gene in postmenopausal women – a pilot study

    PubMed Central

    Grazio, Simeon; Kosovic, Pasezada; Uremovic, Melita; Nemcic, Tomislav; Bobic, Jasminka

    2016-01-01

    Objectives Osteoprotegerin (OPG) has an important role in bone remodeling, and it has been proposed that the OPG gene might be a candidate gene for osteoporosis predisposition. Several studies have already assessed the connection between OPG gene polymorphism and bone mineral density (BMD). In this study we wanted to analyze the association of two polymorphisms in the OPG gene with BMD and bone turnover markers in women with and without osteoporosis. Material and methods In 22 postmenopausal women with osteoporosis (aged 65.6 ±12.6) and 59 women without osteoporosis (aged 60.8 ±8.7) we analyzed the association of two polymorphisms in the OPG gene with BMD, measured by dual energy absorptiometry and with bone turnover markers (crosslaps and osteoprotegerin). A163G, G209A, T245G and G1181C polymorphisms were determined. Results No significant differences in age, anthropometry, number of fractures, osteocalcin and cross-laps were found between women with and without osteoporosis. Women with osteoporosis were significantly longer in postmenopause. Significantly more women with osteoporosis had AG polymorphism (p = 0.038) compared to women without osteoporosis, while no significant difference was found in prevalence of TT and GG polymorphism between patients with and without osteoporosis. No relationship was found between investigated polymorphism and bone turnover markers. A significant negative correlation between total hip BMD and crosslaps (p = 0.046) as well as between total hip T score and crosslaps (p = 0.044) was found in women without osteoporosis Conclusions Postmenopausal women with osteoporosis had AG polymorphism more frequently than women without osteoporosis. Our results indicate that A163G polymorphism could have an impact on higher bone loss in postmenopausal women. PMID:27407270

  1. Candidate genes and late-onset type 2 diabetes mellitus. Susceptibility genes or common polymorphisms?

    PubMed

    Hansen, Lars

    2003-11-01

    985Met variant in the insulin receptor is associated with type 2 diabetes or that the Met326Val of the p85 alpha regulatory subunit of the phosphoinositide-3 kinase is associated with insulin resistance. We found no coding mutations (missense) in the insulin signalling protein kinases but we confirmed that the 5 bp deletion (PP1ARE) in the 3'-end of the PPP1R3 gene that encodes the glycogen-associated regulatory subunit of protein phosphatase-1 (PP1G) is associated with insulin resistance estimated as insulin mediated glucose uptake. In contrast to protein kinases in skeletal muscles the genes encoding beta-cell transcription factors (IPF-1, NeuroD1/BETA2, and Neurogenin 3) are polymorphic but we could not confirm that the Asp76Asn of IPF-1 is a susceptibility gene for late-onset type 2 diabetes. On the other hand we confirmed that the Ala45Thr variant in NeuroD1/BETA2 may represent a susceptibility gene for type 1 diabetes but none of these genes revealed any MODY-specific mutations. Also the gene encoding the ATP-regulatable potassium channels of the beta-cell (Kir6.2) is polymorphic but none of these polymorphisms associated with changes in glucose-induced insulin secretion. Reviewed in context of the existing data our studies support the candidate gene approach as a feasible method for directly either identifying or excluding any gene as a diabetes-susceptibility gene ("diabetogene"). PMID:14694850

  2. Association of NCOA2 gene polymorphisms with obesity and dyslipidemia in the Chinese Han population

    PubMed Central

    Lu, Yuping; Habtetsion, Tsadik Ghebreamlak; Li, Yong; Zhang, Huiping; Qiao, Yichun; Yu, Mingxi; Tang, Yuan; Zhen, Qing; Cheng, Yi; Liu, Yawen

    2015-01-01

    Background: Nuclear receptor coactivator 2 (NCOA2) gene plays an important role in adipogenesis and lipid metabolism. NCOA2 gene null mice exhibited less fat accumulation and lower serum lipid levels, and were protected against obesity. Few studies are known to have analyzed the association of NCOA2 gene single nucleotide polymorphisms with obesity and serum lipid profile. Our study aimed to evaluate the association of NCOA2 gene polymorphisms with the risk of obesity and dyslipidemia in the Chinese Han population. Methods: Two NCOA2 gene polymorphisms (rs41391448 and rs10504473) were selected and genotyped in a Chinese Han cohort with 529 participants. The effect of different genotypes on BMI and serum lipid levels (TG, TC, LDL-C and HDL-C) was performed by the analysis of covariance. Association of NCOA2 polymorphisms with obesity and dyslipidemia was assessed by odds ratios (OR) and 95% confidence intervals (CI) under the unconditional logistic regression analysis. Results: Significant association was observed between rs10504473 polymorphism and obesity under the recessive model (OR = 1.88, 95% CI 1.02-3.45, P = 0.047; adjusted OR = 1.87, 95% CI 1.02-3.44, P = 0.048). However, no association remained significant after Bonferroni correction. Conclusion: Our study suggests a possible association between NCOA2 rs10504473 polymorphism and obesity, and this SNP may influence the susceptibility of obesity in the Chinese Han population. PMID:26261634

  3. Contribution of the GSTP1 gene polymorphism to the development of osteosarcoma in a Chinese population.

    PubMed

    Qu, W R; Wu, J; Li, R

    2016-01-01

    We conducted a case-control study to investigate the associations between GSTT1, GSTM1, and GSTP1 gene polymorphisms and development of osteosarcoma in a Chinese population. Between January 2013 and February 2015, 153 patients diagnosed with osteosarcoma and 252 control subjects were enrolled in the current study from the Orthopedic Hospital of the Second Hospital of Jilin University. The GSTM1, GSTT1, and GSTP1 gene polymorphisms were detected by polymerase chain reaction coupled with restriction fragment length polymorphism analysis. As determined by a multiple-logistic regression analysis, the Val/Val genotype of GSTP1 was associated with a significantly increased risk of osteosarcoma compared to that of the Ile/Ile genotype, with an odds ratio (OR) = 3.39, and a 95% confidence interval (CI) = 1.45-8.13. Moreover, the Ile/Val+Val/Val genotype of GSTP1 was correlated with a marginally significant increased risk of osteosarcoma compared to that of the Ile/Ile genotype (OR = 1.65, 95%CI = 1.08-2.53). However, we did not find any significant associations between the GSTM1 and GSTT1 gene polymorphisms and osteosarcoma risk. In conclusion, our results suggest that the GSTP1 gene polymorphism is associated with an increased risk of osteosarcoma, whereas the GSTM1 and GSTT1 gene polymorphisms may not influence the development of this cancer. PMID:27525908

  4. Clinical relevance of IL-6 gene polymorphism in severely injured patients.

    PubMed

    Jeremić, Vasilije; Alempijević, Tamara; Mijatović, Srđan; Sijački, Ana; Dragašević, Sanja; Pavlović, Sonja; Miličić, Biljana; Krstić, Slobodan

    2014-05-01

    In polytrauma, injuries that may be surgically treated under regular circumstances due to a systemic inflammatory response become life-threatening. The inflammatory response involves a complex pattern of humoral and cellular responses and the expression of related factors is thought to be governed by genetic variations. This aim of this paper is to examine the influence of interleukin (IL) 6 single nucleotide polymorphism (SNP) -174C/G and -596G/A on the treatment outcome in severely injured patients. Forty-seven severely injured patients were included in this study. Patients were assigned an Injury Severity Score. Blood samples were drawn within 24 h after admission (designated day 1) and on subsequent days (24, 48, 72 hours and 7 days) of hospitalization. The IL-6 levels were determined through ELISA technique. Polymorphisms were analyzed by a method of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR). Among subjects with different outcomes, no statistically relevant difference was found with regards to the gene IL-6 SNP-174G/C polymorphism. More than a half of subjects who died had the SNP-174G/C polymorphism, while this polymorphism was represented in a slightly lower number in survivors. The incidence of subjects without polymorphism and those with heterozygous and homozygous gene IL-6 SNP-596G/A polymorphism did not present statistically significant variations between survivors and those who died. The levels of IL-6 over the observation period did not present any statistically relevant difference among subjects without the IL-6 SNP-174 or IL- 6 SNP -596 gene polymorphism and those who had either a heterozygous or a homozygous polymorphism. PMID:24856384

  5. Association of sweet taste receptor gene polymorphisms with dental caries experience in school children.

    PubMed

    Haznedaroğlu, Eda; Koldemir-Gündüz, Meliha; Bakır-Coşkun, Nur; Bozkuş, Hasan M; Çağatay, Penbe; Süsleyici-Duman, Belgin; Menteş, Ali

    2015-01-01

    Sweet taste is a powerful factor influencing food acceptance. The peripheral taste response to sugar is mediated by the TAS1R2/TAS1R3 taste receptors. The aim of the study was to determine the relationship between TAS1R2 (rs35874116 or rs9701796) and/or TAS1R3 (rs307355) single nucleotide polymorphisms with dental caries experience in schoolchildren. A total of 184 schoolchildren aged between 7 and 12 years (101 girls, 83 boys) were included in the study. Genomic DNA was extracted from saliva samples and the genotypes were identified by qPCR. The genotype frequencies were as follows: 6.6% for homozygous wild type, 41.8% for heterozygous and 51.6% for homozygous polymorphic genotype carriers of TAS1R2 gene rs35874116; 27.8% for heterozygous and 72.2% for homozygous polymorphic genotype carriers of TAS1R2 gene rs9701796, and 83.1% for homozygous wild type and 16.9% for heterozygous genotype carriers of TAS1R3 gene rs307355 polymorphism. A significant association was observed between total caries experience (dft + DMFT - decayed filled primary teeth + decayed, missing and filled permanent teeth) and TAS1R2 rs35874116 (p = 0.008) and TAS1R3 rs307355 (p = 0.04) gene polymorphisms but not for TAS1R2 gene rs9701796 polymorphism. TAS1R3 gene rs307355 polymorphism has been found to be an independent risk factor for dental caries experience by logistic regression analysis and to have increased the risk of caries. Moderate caries experience (4-7 caries) was found to be associated with TAS1R3 rs307355 heterozygous genotype, whereas high-risk caries experience (>8 caries) was found to be associated with TAS1R2 rs35874116 homozygous polymorphic genotype. PMID:25924601

  6. Interleukin 2 Gene Polymorphisms Are Associated with Non-Hodgkin Lymphoma

    PubMed Central

    Song, Haihan; Chen, Lei; Cha, Zhanshan

    2012-01-01

    Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy worldwide. Interleukin-2 (IL-2) plays a key role in the proliferation of T cells and natural killer cells. It has been reported that polymorphisms in the IL-2 gene are associated with various cancers. The aim of this study was to examine the effect of polymorphisms in the IL-2 gene on the development of NHL in the Chinese population. IL-2-330T/G and +114T/G polymorphisms were detected by polymerase chain reaction–restriction fragment length polymorphism in 438 NHL cases and 482 age-matched healthy controls. Data were analyzed using the Chi-square test. Results showed that individuals with −330TG genotype or −330GG genotype had significantly increased susceptibility to NHL (Odds ratio [OR]=1.40, 95% confidence interval [CI]: 1.05–1.85, p=0.020 and OR=2.04, 95%CI: 1.28–3.24, p=0.002). Meanwhile, the +114T/G polymorphism did not show any correlation with NHL. When analyzing the haplotypes of these two polymorphisms, the prevalence of −330G/+114T haplotype was significantly higher in NHL cases than in controls (OR=1.45, 95%CI: 1.12–1.88, p=0.005). These data indicate that IL-2 gene polymorphisms may be new risk factors for NHL. PMID:22472080

  7. Genetic polymorphism of estrogen receptor alpha gene in Egyptian women with type II diabetes mellitus

    PubMed Central

    Motawi, Tarek M.K.; El-Rehany, Mahmoud A.; Rizk, Sherine M.; Ramzy, Maggie M.; el-Roby, Doaa M.

    2015-01-01

    Estrogen might play an important role in type 2 diabetes mellitus pathogenesis. A number of polymorphisms have been reported in the estrogen receptor alpha gene including the XbaI and PvuII restriction enzyme polymorphisms. The aim of this study was to determine if ESRα gene polymorphisms are associated with type 2 diabetes mellitus and correlated with lipid profile. Ninety diabetic Egyptian patients were compared with forty healthy controls. ESRα genotyping of PvuII and XbaI was performed using restriction fragment length polymorphism analysis. Our study showed that there is more significant difference in the frequency of C and G polymorphic allele between patients and control groups in PvuII and XbaI respectively. Also carriers of minor C and G alleles of PvuII and XbaI gene polymorphisms were associated with increased fasting blood glucose and disturbance in lipid profile as there is an increase in total cholesterol, triglycerides and Low density lipoprotein. So findings of present study suggest the possibility that PvuII and XbaI polymorphisms in ERα are related to T2DM and with increased serum lipids among Egyptian population. PMID:26401488

  8. Functional Polymorphisms of Matrix Metalloproteinases 1 and 9 Genes in Women with Spontaneous Preterm Birth

    PubMed Central

    Pleša, Ivana; Peterlin, Ana; Jan, Žiga; Tul, Nataša; Kapović, Miljenko; Ostojić, Saša; Peterlin, Borut

    2014-01-01

    Objective. The aim of this study was to investigate the association of functional MMP-1-1607 1G/2G and MMP-9-1562 C/T gene polymorphisms with spontaneous preterm birth (SPTB; preterm birth with intact membranes) in European Caucasian women, as well as the contribution of these polymorphisms to different clinical features of women with SPTB. Methods and Patients. A case-control study was conducted in 113 women with SPTB and 119 women with term delivery (control group). Genotyping of MMP-1-1607 1G/2G and MMP-9-1562 C/T gene polymorphisms was performed using the combination of polymerase chain reaction and restriction fragment length polymorphism methods. Results. There were no statistically significant differences in the distribution of neither individual nor combinations of genotype and allele frequencies of MMP-1-1607 1G/2G and MMP-9-1562 C/T polymorphisms between women with SPTB and control women. Additionally, these polymorphisms do not contribute to any of the clinical characteristics of women with SPTB, including positive and negative family history of SPTB, gestational age at delivery, and maternal age at delivery, nor fetal birth weight. Conclusion. We did not find the evidence to support the association of MMP-1-1607 1G/2G and MMP-9-1562 C/T gene polymorphisms with SPTB in European Caucasian women. PMID:25530657

  9. Association between two single base polymorphisms of intercellular adhesion molecule 1 gene and inflammatory bowel disease

    PubMed Central

    Habibi, Manijeh; Naderi, Nosratllah; Farnood, Alma; Balaii, Hedieh; Dadaei, Tahereh; Almasi, Shohreh; Zojaji, Homayoun; Asadzadeh Aghdae, Hamid; Zali, Mohammad Reza

    2016-01-01

    Aim: The present study evaluated the association between G241R and K469E polymorphisms of intercellular adhesion molecule 1 gene and inflammatory bowel disease in Iranian population. Background: Inflammatory bowel disease including ulcerative colitis and Crohn’s disease, is a chronic idiopathic inflammatory disease of the gastrointestinal tract. There are two single base polymorphisms of intercellular adhesion molecule 1gene, G241R and K469E, reported to be associated with inflammatory disorders. Patients and methods: In this case-control study, 156 inflammatory bowel disease patients (110 ulcerative colitis and 46 Crohn’s disease patients) and 131 healthy controls were enrolled. Two polymorphisms of intercellular adhesion molecule 1 gene, including G241R and K469E, were assessed by polymerase chain reaction followed by restriction fragment length polymorphism. Results: The E469 allele of K469E polymorphism was significantly more frequent in Crohn’s disease patients compared to controls (P< 0.05, OR= 1.83; 95% CI: 1.13 to 2.96). The mutant homozygote genotype of K469E polymorphism (E/E) was also significantly more frequent in Crohn’s disease patients compared to controls (P< 0.05, OR= 4.23; 95% CI: 1.42 to 12.59). No difference was observed in the frequency of K469E polymorphism among ulcerative colitis patients compared to controls. There were no significant differences in genotype and allele frequencies of G241R polymorphism among ulcerative colitis and Crohn’s disease patients compared to control subjects. Conclusion: According to our findings, K469E polymorphism of intercellular adhesion molecule 1 gene may probably participate in the pathogenesis of Crohn’s disease in Iran. PMID:27099667

  10. Tim-3 polymorphism downregulates gene expression and is involved in the susceptibility to ankylosing spondylitis.

    PubMed

    Wang, Mingfei; Ji, Bin; Wang, Jian; Cheng, Xiangyu; Zhou, Qiang; Zhou, Junjie; Cao, Chengfu; Guo, Qunfeng

    2014-10-01

    Ankylosing spondylitis (AS) is a chronic inflammatory disorder primarily affecting the sacroiliac joints and the spine. T-cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) has been established as a negative regulatory molecule that plays a critical role in controlling inflammation. Studies have shown that polymorphisms in TIM-3 gene may be associated with inflammatory diseases. The current study investigated the association between polymorphisms in the TIM-3 gene and susceptibility to AS, and it examined the effects of these polymorphisms on gene expression. Two polymorphisms in TIM-3 -574G/T and +4259T/G polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism in 282 AS patients and 298 healthy controls. Results showed that frequency of the TIM-3 -574GT genotype was significantly increased in cases than in controls (Odd ratio [OR]=2.50, 95% confidence interval [CI]: 1.39-4.48, p=0.002). Similarly, TIM-3 -574T allele revealed a positive association with the disease (OR=2.39, p=0.002). The TIM-3 +4259T/G polymorphism did not show any correlation with AS. We further evaluated TIM-3 mRNA and protein levels in CD4(+) T cells, CD8(+) T cells, and monocytes from subjects carrying different TIM-3 genotypes. Results revealed that subjects carrying polymorphic -574GT genotype had significantly lower TIM-3 mRNA and protein levels in CD4(+) T cells, CD8(+) T cells, and monocytes than those with wild-type GG genotype. These data suggest that TIM-3 polymorphism is associated with increased susceptibility to AS possibly by downregulating gene expression. PMID:24905803

  11. Liver X Receptor Gene Polymorphisms in Tuberculosis: Effect on Susceptibility

    PubMed Central

    Liu, Li-rong; Yue, Jun; Zhao, Yan-lin; Xiao, He-ping

    2014-01-01

    Objectives The Liver X receptors (LXRs), Liver X receptor A (LXRA) and Liver X receptor B (LXRB), regulate lipid metabolism and antimicrobial response. LXRs have a crucial role in the control of Mycobacterium tuberculosis (M.tb). Lacking LXRs mice is more susceptibility to infection M.tb, developing higher bacterial burdens and an increase in the size and number of granulomatous lesions. We aimed to assess the associations between single nucleotide polymorphisms (SNPs) in LXRs and risk of tuberculosis. Methods We sequenced the LXRs genes to detect SNPs and to examine genotypic frequencies in 600 patients and 620 healthy controls to investigate for associations with tuberculosis (TB) in the Chinese Han population. DNA re-sequencing revealed eight common variants in the LXRs genes. Results The G allele of rs1449627 and the T allele of rs1405655 demonstrated an increased risk of developing TB (p<0.001, p = 0.002), and the T allele of rs3758673, the T allele of rs2279238, and the C allele of rs1449626 in LXRA and the C allele of rs17373080, the G allele of rs2248949, and the C allele of rs1052677 in LXRB were protective against TB patients compared to healthy controls (p = 0.0002, p = 0.006, p<0.001, p = 0.004, p = 0.008, p = 0.003, respectively). All SNP genotypes were significantly associated with TB. An estimation of the frequencies of haplotypes revealed two potential risk haplotypes,GGCG in LXRB (p = 0.004,) and TTCG in LXRA (p<0.001, p = 0.004). Moreover, three protective haplotypes, TTAT and CCAT in LXRA and CATC in LXRB, were significantly “protective” (p = 0.008, p<0.001, p = 0.031) for TB. Furthermore, we determined that the LXRs SNPs were nominally associated with the clinical pattern of disease. Conclusions Our study data supported that LXRs play a fundamental role in the genetic susceptibility to TB and to different clinical patterns of disease. Thus, further investigation is required in larger populations and in

  12. Adiponectin Genotype, Blood Pressures, and Arterial Stiffness: The Cardiometabolic Risk in Chinese (CRC) Study.

    PubMed

    Liang, Jun; Qiu, Qinqin; Gong, Ying; Liu, Xuekui; Dou, Lianjun; Zou, Caiyan; Wang, Yu; Qi, Lu

    2015-05-01

    The authors examined whether the adiponectin gene (ADIPOQ) variant was associated with blood pressure and arterial stiffness in Chinese adults. A genome-wide association study of the adiponectin variant rs864265 in the ADIPOQ gene was genotyped in a total of 2364 participants. After adjustment for sex, age, body mass index (BMI), fasting glucose, and lipids, participants carrying the T allele of rs864265 showed a greater increase in carotid-femoral pulse wave velocity (cfPWV) and systolic blood pressure (SBP). Further adjustment for blood pressure did not appreciably change the association with cfPWV. The authors found significant interactions between rs864265 and BMI, waist circumference, body fat percentage, and SBP in relation to cfPWV (P for interaction = .035, .001, .003, .013, respectively). The T allele of rs864265 was associated with high blood pressure and arterial stiffness. BMI, body fat percentage, waist circumference, and SBP might modify the effects of genetic polymorphism on arterial stiffness. PMID:25894102

  13. Polymorphism analysis of prion protein gene in 11 Pakistani goat breeds.

    PubMed

    Hassan, Mohammad Farooque; Khan, Sher Hayat; Babar, Masroor Ellahi; Yang, Lifeng; Ali, Tariq; Khan, Jamal Muhammad; Shah, Syed Zahid Ali; Zhou, Xiangmei; Hussain, Tanveer; Zhu, Ting; Hussain, Tariq; Zhao, Deming

    2016-07-01

    The association between caprine PrP gene polymorphisms and its susceptibility to scrapie has been investigated in current years. As the ORF of the PrP gene is extremely erratic in different breeds of goats, we studied the PrP gene polymorphisms in 80 goats which belong to 11 Pakistani indigenous goat breeds from all provinces of Pakistan. A total of 6 distinct polymorphic sites (one novel) with amino acid substitutions were identified in the PrP gene which includes 126 (A -> G), 304 (G -> T), 379 (A -> G), 414 (C -> T), 428 (A -> G) and 718 (C -> T). The locus c.428 was found highly polymorphic in all breeds as compare to other loci. On the basis of these PrP variants NJ phylogenetic tree was constructed through MEGA6.1 which showed that all goat breeds along with domestic sheep and Mauflon sheep appeared as in one clade and sharing its most recent common ancestors (MRCA) with deer species while Protein analysis has shown that these polymorphisms can lead to varied primary, secondary and tertiary structure of protein. Based on these polymorphic variants, genetic distance, multidimensional scaling plot and principal component analyses revealed the clear picture regarding greater number of substitutions in cattle PrP regions as compared to the small ruminant species. In particular these findings may pinpoint the fundamental control over the scrapie in Capra hircus on genetic basis. PMID:27388702

  14. Adaptive gains through repeated gene loss: parallel evolution of cyanogenesis polymorphisms in the genus Trifolium (Fabaceae)

    PubMed Central

    Olsen, Kenneth M.; Kooyers, Nicholas J.; Small, Linda L.

    2014-01-01

    Variation in cyanogenesis (hydrogen cyanide release following tissue damage) was first noted in populations of white clover more than a century ago, and subsequent decades of research have established this system as a classic example of an adaptive chemical defence polymorphism. Here, we document polymorphisms for cyanogenic components in several relatives of white clover, and we determine the molecular basis of this trans-specific adaptive variation. One hundred and thirty-nine plants, representing 13 of the 14 species within Trifolium section Trifoliastrum, plus additional species across the genus, were assayed for cyanogenic components (cyanogenic glucosides and their hydrolysing enzyme, linamarase) and for the presence of underlying cyanogenesis genes (CYP79D15 and Li, respectively). One or both cyanogenic components were detected in seven species, all within section Trifoliastrum; polymorphisms for the presence/absence (PA) of components were detected in six species. In a pattern that parallels our previous findings for white clover, all observed biochemical polymorphisms correspond to gene PA polymorphisms at CYP79D15 and Li. Relationships of DNA sequence haplotypes at the cyanogenesis loci and flanking genomic regions suggest independent evolution of gene deletions within species. This study thus provides evidence for the parallel evolution of adaptive biochemical polymorphisms through recurrent gene deletions in multiple species. PMID:24958921

  15. Evaluation of ICAM-1 and VCAM-1 Gene Polymorphisms in Patients with Periodontal Disease

    PubMed Central

    Wang, Li; Li, Xiao-Hong; Ning, Wan-Chen

    2016-01-01

    Background We aimed to investigate the potential genetic relationships between the polymorphisms of gene rs5498 ICAM-1 and rs1041163 VCAM-1 and chronic periodontitis in a Chinese population within Heilongjiang. Material/Methods Genomic DNA was extracted from oral mucosa cells of 584 periodontal patients and 182 healthy individuals. Genotyping of the rs5498 ICAM-1 and rs1041163 VCAM-1 gene polymorphisms was performed with the Multiplex SNaPshot technique. Results Statistically significant associations were identified between the chronic periodontal patients and the controls in the gene polymorphisms of rs5498 ICAM-1 (P=0.007) and rs1041163 VCAM-1 (P=0.029). The distribution of rs5498 (P=0.029) and rs1041163 (P=0.049) differed significantly across the mild, moderate, and severe groups of periodontitis. Conclusions Our findings indicate that ICAM-1 rs5498 and VCAM-1 rs1041163 polymorphisms contribute to chronic periodontitis, and ICAM-1 rs5498 and VCAM-1 rs1041163 gene polymorphisms might be associated with periodontitis severity in the Heilongjiang Chinese population. Further studies should be conducted to determine whether these polymorphisms could be used as biomarkers of periodontitis. PMID:27391418

  16. Evaluation of ICAM-1 and VCAM-1 Gene Polymorphisms in Patients with Periodontal Disease.

    PubMed

    Wang, Li; Li, Xiao-Hong; Ning, Wan-Chen

    2016-01-01

    BACKGROUND We aimed to investigate the potential genetic relationships between the polymorphisms of gene rs5498 ICAM-1 and rs1041163 VCAM-1 and chronic periodontitis in a Chinese population within Heilongjiang. MATERIAL AND METHODS Genomic DNA was extracted from oral mucosa cells of 584 periodontal patients and 182 healthy individuals. Genotyping of the rs5498 ICAM-1 and rs1041163 VCAM-1 gene polymorphisms was performed with the Multiplex SNaPshot technique. RESULTS Statistically significant associations were identified between the chronic periodontal patients and the controls in the gene polymorphisms of rs5498 ICAM-1 (P=0.007) and rs1041163 VCAM-1 (P=0.029). The distribution of rs5498 (P=0.029) and rs1041163 (P=0.049) differed significantly across the mild, moderate, and severe groups of periodontitis. CONCLUSIONS Our findings indicate that ICAM-1 rs5498 and VCAM-1 rs1041163 polymorphisms contribute to chronic periodontitis, and ICAM-1 rs5498 and VCAM-1 rs1041163 gene polymorphisms might be associated with periodontitis severity in the Heilongjiang Chinese population. Further studies should be conducted to determine whether these polymorphisms could be used as biomarkers of periodontitis. PMID:27391418

  17. ACC2 gene polymorphisms, metabolic syndrome, and gene-nutrient interactions with dietary fat

    PubMed Central

    Phillips, Catherine M.; Goumidi, Louisa; Bertrais, Sandrine; Field, Martyn R.; Cupples, L. Adrienne; Ordovas, Jose M.; McMonagle, Jolene; Defoort, Catherine; Lovegrove, Julie A.; Drevon, Christian A.; Blaak, Ellen E.; Kiec-Wilk, Beata; Riserus, Ulf; Lopez-Miranda, Jose; McManus, Ross; Hercberg, Serge; Lairon, Denis; Planells, Richard; Roche, Helen M.

    2010-01-01

    Acetyl-CoA carboxylase β (ACC2) plays a key role in fatty acid synthesis and oxidation pathways. Disturbance of these pathways is associated with impaired insulin responsiveness and metabolic syndrome (MetS). Gene-nutrient interactions may affect MetS risk. This study determined the relationship between ACC2 polymorphisms (rs2075263, rs2268387, rs2284685, rs2284689, rs2300453, rs3742023, rs3742026, rs4766587, and rs6606697) and MetS risk, and whether dietary fatty acids modulate this in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1754). Minor A allele carriers of rs4766587 had increased MetS risk (OR 1.29 [CI 1.08, 1.58], P = 0.0064) compared with the GG homozygotes, which may in part be explained by their increased body mass index (BMI), abdominal obesity, and impaired insulin sensitivity (P < 0.05). MetS risk was modulated by dietary fat intake (P = 0.04 for gene-nutrient interaction), where risk conferred by the A allele was exacerbated among individuals with a high-fat intake (>35% energy) (OR 1.62 [CI 1.05, 2.50], P = 0.027), particularly a high intake (>5.5% energy) of n-6 polyunsaturated fat (PUFA) (OR 1.82 [CI 1.14, 2.94], P = 0.01; P = 0.05 for gene-nutrient interaction). Saturated and monounsaturated fat intake did not modulate MetS risk. Importantly, we replicated some of these findings in an independent cohort. In conclusion, the ACC2 rs4766587 polymorphism influences MetS risk, which was modulated by dietary fat, suggesting novel gene-nutrient interactions. PMID:20855566

  18. Adiponectin enhances the responsiveness of the olfactory system.

    PubMed

    Loch, Diana; Heidel, Christian; Breer, Heinz; Strotmann, Jörg

    2013-01-01

    The peptide hormone adiponectin is secreted by adipose tissue and the circulating concentration is reversely correlated with body fat mass; it is considered as starvation signal. The observation that mature sensory neurons of the main olfactory epithelium express the adiponectin receptor 1 has led to the concept that adiponectin may affect the responsiveness of the olfactory system. In fact, electroolfactogram recordings from olfactory epithelium incubated with exogenous adiponectin resulted in large amplitudes upon odor stimulation. To determine whether the responsiveness of the olfactory sensory neurons was enhanced, we have monitored the odorant-induced expression of the immediate early gene Egr1. It was found that in an olfactory epithelium incubated with nasally applied adiponectin the number of Egr1 positive cells was significantly higher compared to controls, suggesting that adiponectin rendered the olfactory neurons more responsive to an odorant stimulus. To analyze whether the augmented responsiveness of sensory neurons was strong enough to elicit a higher neuronal activity in the olfactory bulb, the number of activated periglomerular cells of a distinct glomerulus was determined by monitoring the stimulus-induced expression of c-fos. The studies were performed using the transgenic mOR256-17-IRES-tauGFP mice which allowed to visualize the corresponding glomerulus and to stimulate with a known ligand. The data indicate that upon exposure to 2,3-hexanedione in adiponectin-treated mice the number of activated periglomerular neurons was significantly increased compared to controls. The results of this study indicate that adiponectin increases the responsiveness of the olfactory system, probably due to a higher responsiveness of olfactory sensory neurons. PMID:24130737

  19. Adiponectin Enhances the Responsiveness of the Olfactory System

    PubMed Central

    Loch, Diana; Heidel, Christian; Breer, Heinz; Strotmann, Jörg

    2013-01-01

    The peptide hormone adiponectin is secreted by adipose tissue and the circulating concentration is reversely correlated with body fat mass; it is considered as starvation signal. The observation that mature sensory neurons of the main olfactory epithelium express the adiponectin receptor 1 has led to the concept that adiponectin may affect the responsiveness of the olfactory system. In fact, electroolfactogram recordings from olfactory epithelium incubated with exogenous adiponectin resulted in large amplitudes upon odor stimulation. To determine whether the responsiveness of the olfactory sensory neurons was enhanced, we have monitored the odorant-induced expression of the immediate early gene Egr1. It was found that in an olfactory epithelium incubated with nasally applied adiponectin the number of Egr1 positive cells was significantly higher compared to controls, suggesting that adiponectin rendered the olfactory neurons more responsive to an odorant stimulus. To analyze whether the augmented responsiveness of sensory neurons was strong enough to elicit a higher neuronal activity in the olfactory bulb, the number of activated periglomerular cells of a distinct glomerulus was determined by monitoring the stimulus-induced expression of c-fos. The studies were performed using the transgenic mOR256-17-IRES-tauGFP mice which allowed to visualize the corresponding glomerulus and to stimulate with a known ligand. The data indicate that upon exposure to 2,3-hexanedione in adiponectin-treated mice the number of activated periglomerular neurons was significantly increased compared to controls. The results of this study indicate that adiponectin increases the responsiveness of the olfactory system, probably due to a higher responsiveness of olfactory sensory neurons. PMID:24130737

  20. Human T-cell receptor v{beta} gene polymorphism and multiple sclerosis

    SciTech Connect

    Wei, S.; Charmley, P.; Birchfield, R.I.; Concannon, P.

    1995-04-01

    Population-based genetic associations have been reported between RFLPs detected with probes corresponding to the genes encoding the {beta} chain of the T-cell receptor for antigen (RCRB) and a variety of autoimmune disorders. In the case of multiple sclerosis (MS), these studies have localized a putative disease-associated gene to a region of {approximately}110 kb in length, located within the TCRB locus. In the current study, all 14 known TCRBV (variable region) genes within the region of localization were mapped and identified. The nucleotide sequences of these genes were determined in a panel of six MS patients and six healthy controls, who were human-leukocyte antigen and TCRB-RFLP haplotype matched. Nine of the 14 TCRBV genes studied showed evidence of polymorphism. PCR-based assays for each of these polymorphic genes were developed, and allele and genotype frequencies were determined in a panel of DNA samples from 48 MS patients and 60 control individuals. No significant differences in allele, genotype, or phenotype frequencies were observed between the MS patients and controls for any of the 14 TCRBV-gene polymorphisms studied. In light of the extensive linkage disequilibrium across the region studied, the saturating numbers of polymorphisms examined, and the direct sequence analysis of all BV genes in the region, these results suggest that it is unlikely that germ-line polymorphism in the TCRBV locus makes a major contribution to MS susceptibility. The TCRBV coding region-specific markers generated in these studies, as well as the approach of testing for associations with specific functionally relevant polymorphic sites within individual BV genes, should be useful in the evaluation of the many reported disease associations involving the human TCRB region. 22 refs., 1 fig., 3 tabs.

  1. Endothelial nitric oxide synthase gene polymorphism is associated with Legg-Calvé-Perthes disease

    PubMed Central

    ZHAO, YULONG; LIAO, SHIJIE; LU, RONGBIN; DANG, HAO; ZHAO, JINMIN; DING, XIAOFEI

    2016-01-01

    The aim of this study was to assess the association of 27-bp variable number tandem repeat (VNTR) polymorphism in intron 4 and G894T polymorphism in exon 7 of the endothelial nitric oxide synthase (eNOS) gene with Legg-Calvé-Perthes disease (LCPD), and to provide a scientific basis for further research into the pathogenic mechanism. A total of 80 patients with LCPD and 100 healthy subjects were recruited in this case-control study. The 27-bp VNTR and G894T polymorphisms of the eNOS gene were genotyped using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism, respectively, followed by agarose gel electrophoresis and DNA sequencing. Allelic and genotypic frequencies were computed in the two groups and subjected to statistical analysis. For the 27-bp VNTR polymorphism, individuals with LCPD showed a higher frequency of the ab genotype [27.5 vs. 14%; odds ratio (OR), 2.33; 95% confidence interval (CI), 1.10–4.92; P=0.024]. For the G894T polymorphism, the LCPD case group showed a higher frequency of the heterozygous genotype GT than the healthy control group (35 vs. 17%; OR, 2.67; 95% CI, 1.33–5.36; P=0.005). The results indicate that these eNOS gene polymorphisms may be a risk factor for LCPD. The 27-bp VNTR polymorphism in intron 4 and G894T polymorphism in exon 7 may be involved in the etiology of LCPD. PMID:27168827

  2. Detection of DNA sequence polymorphisms in carcinogen metabolism genes by polymerase chain reaction.

    PubMed

    Bell, D A

    1991-01-01

    The glutathione transferase mu gene (GST1) and the debrisoquine hydroxylase gene (CYP2D6) are known to be polymorphic in the human population and have been associated with increased susceptibility to cancer. Smokers with low lymphocyte GST mu activity are at higher risk for lung cancer, while low debrisoquine hydroxylase activity has been correlated with lower risk for lung and bladder cancer. Phenotypic characterization of these polymorphisms by lymphocyte enzyme activity (GST) and urine metabolite ratios (debrisoquine) is cumbersome for population studies. Recent cloning and sequencing of the mutant alleles of these genes has allowed genotyping via the polymerase chain reaction (PCR). Advantages of PCR approaches are speed, technical simplicity, and minimal sample requirements. This article reviews the PCR-based methods for detection of genetic polymorphisms in human cancer susceptibility genes. PMID:1684153

  3. Methylenetetrahydrofolate Reductase Gene Polymorphisms in Children with Attention Deficit Hyperactivity Disorder

    PubMed Central

    Gokcen, Cem; Kocak, Nadir; Pekgor, Ahmet

    2011-01-01

    Objective: The purpose of this study was to evaluate the relationship between 5,10- methylenetetrahydrofolate reductase (MTHFR) polymorphisms and Attention Deficit Hyperactivity Disorder (ADHD) in a sample of Turkish children. Study Design: MTHFR gene polymorphisms were assessed in 40 patients with ADHD and 30 healty controls. Two mutations in the MTHFR gene were investigated using polymerase chain reactions and restriction fragment length polymorphisms. Results: Although there were no statistically significant differences in genotype distributions of the C677T alleles between the ADHD and the control groups (p=0,678) but the genotypic pattern of the distributions of the A1298C alleles was different between the ADHD patients and the controls (p=0,033). Conclusions: Preliminary data imply a possible relationship between A1298C MTHFR polymorphisms and the ADHD. PMID:21897766

  4. An improved polymerase chain reaction-restriction fragment length polymorphism assay for the detection of a PON2 gene polymorphism

    PubMed Central

    DUAN, XIAORAN; YANG, YONGLI; WANG, TUANWEI; FENG, XIAOLEI; YAO, WU; YAN, ZHEN; WANG, WEI

    2016-01-01

    In recent research, it has been shown that there have been variants of rs12026 within the paraoxonase 2 (PON2) gene, which have been associated with cardiovascular disease, cerebrovascular disease, diabetes and other diseases. The isochizomers, such as the BsoFI enzyme, required for the detection of this polymorphism are expensive. Therefore, an improved and less expensive polymerase chain reaction (PCR)-restriction fragment length polymorphism method was established for the detection of the single-nucleotide polymorphism rs12026 in the exon 5 of chromosome 7 of the human PON2 gene using the method of amplification-created restriction site. Subsequent to assessing 302 individuals, the genotype frequencies were 68.9% for CC, 29.8% for CG and 1.3% for GG, and the allelic frequencies were 83.8% for C and 16.2% for G. The PCR results were confirmed by DNA sequencing. The χ2 test showed that the genotype and allele frequencies of PON2-148 do not deviate from Hardy-Weinberg equilibrium, and the sequences of amplified products were consistent with the sequence published in GenBank with the exception of a mismatched base. PMID:27330753

  5. Dopamine D4 receptor gene polymorphism and personality traits in healthy volunteers.

    PubMed

    Persson, M L; Wasserman, D; Geijer, T; Frisch, A; Rockah, R; Michaelovsky, E; Apter, A; Weizman, A; Jönsson, E G; Bergman, H

    2000-01-01

    An association between long alleles of a variable number tandem repeat (VNTR) polymorphism in the dopamine receptor D4 gene and the extraversion related personality traits Excitement and Novelty Seeking has been reported in healthy subjects. In an attempt to replicate the previous findings, 256 healthy Caucasian volunteers were analysed for a potential relationship between the dopamine receptor D4 exon III VNTR polymorphism and Extraversion as assessed by the Revised Neo Personality Inventory (NEO PI-R). The present study did not yield evidence for an association between Extraversion and the dopamine receptor D4 polymorphism. PMID:11009073

  6. Enhanced adiponectin actions by overexpression of adiponectin receptor 1 in macrophages

    PubMed Central

    Luo, Nanlan; Chung, B Hong; Wang, Xiangdong; Klein, Richard L.; Tang, Chao-Ke; Garvey, W. Timothy; Fu, Yuchang

    2013-01-01

    Objective Adiponectin is one of several important, metabolically active cytokines secreted from adipose tissue. Epidemiologic studies have associated low circulating levels of this adipokine with multiple metabolic disorders including obesity, insulin resistance, type II diabetes, and cardiovascular disease. To investigate how enhanced adiponectin-mediated changes in metabolism in vivo, we generated transgenic mice which specifically overexpress the gene coding for adiponectin receptor 1 (AdipoR1) in mouse macrophages using the human scavenger receptor A-I gene (SR-AI) enhancer/promoter. We found that macrophage-specific AdipoR1 transgenic mice (AdR1-TG) presented reduced whole body weight, fat accumulation and liver steatosis when these transgenic mice were fed with a high fat diet. Moreover, these macrophage AdR1-TG mice exhibited enhanced whole-body glucose tolerance and insulin sensitivity with reduced proinflammatory cytokines, MCP-1 and TNF-α, both in the serum and in the insulin target metabolic tissues. Additional studies demonstrated that these macrophage AdR1-TG animals exhibited reduced macrophage foam cell formation in the arterial wall when these transgenic mice were crossed with a low-density lipoprotein receptor (Ldlr) deficient mouse model. Conclusions These results suggest that AdipoR1 overexpressed in macrophages can physiologically modulate metabolic activities in vivo by enhancing adiponectin actions in distal metabolically active tissues. The AdipoR1 modified macrophages provide unique interactions with the residented tissues/cells, suggesting a novel role of macrophage adiponectin receptor in improving metabolic disorders in vivo. PMID:23510830

  7. Combined folate gene MTHFD and TC polymorphisms as maternal risk factors for Down syndrome in China.

    PubMed

    Liao, Y P; Zhang, D; Zhou, W; Meng, F M; Bao, M S; Xiang, P; Liu, C Q

    2014-01-01

    We examined whether polymorphisms in the methylenetetrahydrofolate dehydrogenase (MTHFD) and transcobalamin (TC) genes, which are involved in folate metabolism, affect maternal risk for Down syndrome. We investigated 76 Down syndrome mothers and 115 control mothers from Bengbu, China. Genomic DNA was isolated from the peripheral lymphocytes. Polymerase chain reaction and restriction fragment length polymorphism were used to examine the polymorphisms of MTHFD G1958A and TC C776G. The frequencies of the polymorphic alleles were 24.3 and 19.1% for MTHFD 1958A, 53.9 and 54.2% for TC 776G, in the case and control groups, respectively. No significant differences were found between two groups in relation to either the allele or the genotype frequency for both polymorphisms. However, when gene-gene interactions between these two polymorphisms together with previous studied C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene were analyzed, the combined MTHFR 677CT/TT and MTHFD 1958AA/GA genotype was found to be significantly associated with the risk of having a Down syndrome child [odds ratio (OR) = 3.11; 95% confidence interval (95%CI) = 1.07-9.02]. In addition, the combined TC 776CG and MTHFR 677TT genotype increased the risk of having a child with Down syndrome 3.64-fold (OR = 3.64; 95%CI = 1.28-10.31). In conclusion, neither MTHFD G1958A nor TC C776G polymorphisms are an independent risk factor for Down syndrome. However, the combined MTHFD/MTHFR, TC/MTHFR genotypes play a role in the risk of bearing a Down syndrome child in the Chinese population. PMID:24668664

  8. The polymorphisms in the MGMT gene and the risk of cancer: a meta-analysis.

    PubMed

    Du, Liang; Wang, Haichuan; Xiong, Tianyuan; Ma, Yaxian; Yang, Jiqiao; Huang, Jichong; Zeng, Dong; Wang, Xiaoze; Huang, He; Huang, Jin

    2013-10-01

    Polymorphisms in the MGMT gene have been implicated in susceptibility to cancer, but the published studies have reported inconclusive results. The objective of the current study was to investigate the genetic risk of polymorphisms in the MGMT gene for cancer. A meta-analysis was carried out to analyze the association between polymorphisms in the MGMT gene and cancer risk. Five polymorphisms (Leu84Phe, Leu53Leu, Ile143Val, Lys178Arg, and -485C/A) with 98 case-control studies from 49 articles were analyzed. The results indicated that individuals who carried the Phe/Phe homozygote genotype of Leu84Phe had a 31 % increased risk of cancer compared with the Leu allele (Leu + Leu/Phe) carriers (odds ratio [OR] = 1.32, 95 % confidence interval [CI] = 1.15-1.52, P < 0.0001 for Phe/Phe vs. Phe/Leu + Leu/Leu). However, there was no significant association between the risk of cancer and the other four polymorphisms (Leu53Leu, Ile143Val, Lys178Arg, and -485C/A). In further stratified analyses for the Leu84Phe and Ile143Val polymorphisms, the increased risk of cancer remained in subgroups of Caucasians, patients with esophageal cancer for the Leu84Phe polymorphism, and patients with lung cancer for the Ile143Val polymorphism. Results from the current meta-analysis suggested that Leu84Phe and Ile143Val in the MGMT gene are risk factors for cancer. In the future, more studies should be performed to validate our results. PMID:23760981

  9. Vitamin D receptor gene ApaI polymorphism and breast cancer susceptibility: a meta-analysis.

    PubMed

    Luo, Shayang; Guo, Lei; Li, Yan; Wang, Shouman

    2014-01-01

    Vitamin D receptor (VDR) principally mediates the anticancer activities of vitamin D. Many studies investigated the association between VDR gene ApaI polymorphism and breast cancer, but the results were inconclusive. We performed this meta-analysis to evaluate the association between VDR gene ApaI polymorphism and breast cancer. Twelve studies with a total of 8,254 subjects were identified from PubMed and Wanfang databases. The pooled odds ratio (OR) and confidence intervals (95% CI) were used to assess the association. The meta-analysis indicated that VDR gene ApaI polymorphism was not associated with risk of breast cancer (a vs. A: OR = 0.97, 95% CI 0.91-1.04, P = 0.378; aa vs. AA: OR = 0.97, 95% CI 0.85-1.10, P = 0.618; aa vs. AA + Aa: OR = 1.00, 95% CI 0.89-1.12, P = 0.972; aa + Aa vs. AA: OR = 0.95, 95% CI 0.82-1.11, P = 0.550). Subgroup analysis by ethnicity further showed that VDR gene ApaI polymorphism was not associated with risk of breast cancer in both Asians and Caucasians. These data from the meta-analysis indicate that VDR gene ApaI polymorphism is not associated with breast cancer susceptibility. PMID:24048755

  10. Association between the XPG gene Asp1104His polymorphism and lung cancer risk.

    PubMed

    Zhou, B; Hu, X M; Wu, G Y

    2016-01-01

    It has been suggested that the xeroderma pigmentosum complementation group G (XPG) gene Asp1104His polymorphism is linked to susceptibility to lung cancer. However, the results from the published studies are contradictory rather than conclusive. With this meta-analysis, we aimed to achieve a better understanding of the effects of the XPG gene Asp1104His polymorphism on lung cancer risk. We identified six eligible studies from five publications that included a total of 2293 lung cancer patients and 2586 controls. There was a significant association between the XPG gene Asp1104His polymorphism and lung cancer (His/His vs Asp/Asp: OR = 1.24, 95%CI = 1.04-1.48; Asp/His vs Asp/Asp: OR = 1.17, 95%CI = 1.03-1.34; the dominant model: OR = 1.18, 95%CI = 1.04-1.33; the recessive model: OR = 1.10, 95%CI = 0.94-1.28). In a subgroup analysis by nationality, we found a significant association between the XPG gene Asp1104His polymorphism and lung cancer risk in Asians. No publication bias was found in this study. The results from this meta-analysis indicate that the XPG gene Asp1104His polymorphism is associated with lung cancer risk, especially in Asians. PMID:27323149

  11. Serum homocysteine, vitamin B12, folic acid levels and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism in vitiligo.

    PubMed

    Yasar, Ali; Gunduz, Kamer; Onur, Ece; Calkan, Mehmet

    2012-01-01

    The aim of this study was to determine serum vitamin B12, folic acid and homocysteine (Hcy) levels as well as MTHFR (C677, A1298C) gene polymorphisms in patients with vitiligo, and to compare the results with healthy controls. Forty patients with vitiligo and 40 age and sex matched healthy subjects were studied. Serum vitamin B12 and folate levels were determined by enzyme-linked immunosorbent assay. Plasma Hcy levels and MTHFR polymorphisms were determined by chemiluminescence and real time PCR methods, respectively. Mean serum vitamin B12 and Hcy levels were not significantly different while folic acid levels were significantly lower in the control group. There was no significant relationship between disease activity and vitamin B12, folic acid and homocystein levels. No significant difference in C677T gene polymorphism was detected. Heterozygote A1298C gene polymorphism in the patient group was statistically higher than the control group. There was no significant relationship between MTHFR gene polymorphisms and vitamin B12, folic acid and homocysteine levels. In conclusion, vitamin B12, folate and Hcy levels are not altered in vitiligo and MTHFR gene mutations (C677T and A1298C) do not seem to create susceptibility for vitiligo. PMID:22846211

  12. Relationship between EPHX2 gene polymorphisms and essential hypertension in Uygur, Kazakh, and Han.

    PubMed

    Zhu, X L; Wang, L; Wang, Z; Chen, S Z; Zhang, W Q; Ma, M M

    2015-01-01

    We investigated the association between rs751141 polymorphisms in the EPHX2 gene and essential hypertension in Uygur, Kazakh, and Han subjects in Xinjiang, China. A total of 302 essential hypertensive patients in Uygur, 267 in Kazakh, and 368 in Han, as well as 323 normotensive controls in Uygur, 284 in Kazakh, and 348 in Han were enrolled in this study. The TaqMan assay was used to detect the rs751141 G/A gene polymorphism in EPHX2. The rs751141 G/A genotype frequencies for the GA+AA genotypes were 40.2% in essential hypertensive subjects and 52.0% in control subjects in the Han population. The frequencies were significantly different between the 2 Han groups (P < 0.01). The rs751141G/A gene polymorphism showed no significant difference between essential hypertensive patients and normotensive controls in Kazakh and Uygur (all P > 0.05). Essential hypertension in Xinjiang was associated with the rs751141 G/A allele gene polymorphism in EPHX2 in Han subjects but not in Kazakh and Uygur subjects. The rs751141 allele gene polymorphism may be an independent protective factor against essential hypertension in the Han population. PMID:25966114

  13. Association between genetic polymorphisms in cytokine genes and recurrent miscarriage--a meta-analysis.

    PubMed

    Medica, Igor; Ostojic, Sasa; Pereza, Nina; Kastrin, Andrej; Peterlin, Borut

    2009-09-01

    A meta-analysis of association studies was performed to assess whether the reported genetic polymorphisms in cytokine genes are risk factors for recurrent miscarriage (RM). The electronic PubMed database was searched for case-control studies on immunity-related genes in RM. Investigations of a single polymorphism/gene involvement in RM reported more than five times were selected. Aggregating data from seven case-control studies on -308/tumour necrosis factor-alpha polymorphism, the odds ratio (OR) for RM was 1.1 (0.87-1.39) if the polymorphism was considered under a dominant genetic model. In six studies on -1082/interleukin-10 (IL-10) polymorphism, the OR under a dominant model was 0.76 (0.58-0.99), and under a recessive model the OR was 0.90 (0.71-1.15). In five case-control studies on -174/IL-6 polymorphism, the OR for RM under a recessive model was 1.29 (0.69-2.40). The results show a statistically significant association with RM for the -1082/IL-10 genotype. PMID:19778488

  14. Candidate gene polymorphisms and risk of psoriasis: A pilot study

    PubMed Central

    VILLARREAL-MARTÍNEZ, ALEJANDRA; GALLARDO-BLANCO, HUGO; CERDA-FLORES, RICARDO; TORRES-MUÑOZ, IRIS; GÓMEZ-FLORES, MINERVA; SALAS-ALANÍS, JULIO; OCAMPO-CANDIANI, JORGE; MARTÍNEZ-GARZA, LAURA

    2016-01-01

    Psoriasis is a complex genetic disease, which has previously been associated with numerous single nucleotide polymorphisms (SNPs) that are implicated in various processes, including skin barrier functions and in the regulation of inflammatory and immune responses. The present study aimed to investigate the genotypic and allelic frequencies of 32 SNPs at 24 genetic loci, and their association with psoriasis in a Mexican population. These SNPs, which were associated with psoriasis in previous studies, included the following genes: Major histocompatibility complex class I-C (HLA-C), interleukin (IL)-12B, IL-23R, IL-23A, IL-28RA, tumor necrosis factor (TNF)-α, ring finger protein-114 (RNF114), cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1, late cornified envelope 3B/3C, signal transducer and activator of transcription 4, LINC01185, interferon induced with helicase C domain 1, IL-13, TNF-α-induced protein 3 (TNFAIP3), TNFAIP3 interacting protein 1, endoplasmic reticulum aminopeptidase 1, TNF receptor-associated factor interacting protein 2, Leptin, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha, F-box and leucine-rich repeat protein 19, nitric oxide synthase 2, cluster of differentiation 40, nuclear receptor coactivator 5, and ADAM metallopeptidase domain 33. A total of 32 male and 14 female subjects with a clinical diagnosis of chronic plaque psoriasis, as well as 103 control subjects, were analyzed. Molecular analyses were performed using TaqMan® assays in a TaqMan® OpenArray® Genotyping system. Results were analyzed using the Golden Helix SNP and Variation Suite 7 program. Of the 32 SNPs, six were associated with an increased risk of developing psoriasis, including: HLA-C rs10484554 [allele T: odds ratio (OR) 3.51], IL-12B rs3212227 (allele T: OR 1.88), IL-12B rs3213094 (allele C: OR 1.94), HLA complex group 27 rs1265181 (allele C: OR 2.83), annexin A6 rs17728338 (allele A: OR 2.41), and RNF114 rs

  15. Vitamin D receptor gene polymorphisms in breast and renal cancer: current state and future approaches (review).

    PubMed

    Khan, Mohammed I; Bielecka, Zofia F; Najm, Mohammad Z; Bartnik, Ewa; Czarnecki, Jerzy S; Czarnecka, Anna M; Szczylik, Cezary

    2014-02-01

    Cancer is a major health problem and cause of death worldwide that accounted for 7.6 million deaths in 2008, which is projected to continue rising with an estimated 13.1 million deaths in 2030 according to WHO. Breast cancer is the leading cause of cancer-based death among women around the world and its incidence is increasing annually with a similar tendency. In contrast, renal cell carcinoma accounts for only 3% of total human malignancies but it is still the most common type of urological cancer with a high prevalence in elderly men (>60 years of age). There are several factors linked with the development of renal cell cancer only, while others are connected only with breast cancer. Genetic risk factors and smoking are the factors which contribute to carcinogenesis in general. Some evidence exists indicating that vitamin D receptor (VDR) gene polymorphisms are associated with both breast and renal cancer; therefore, we put forward the hypothesis that polymorphisms in the VDR gene may influence both the occurrence risks of these cancers and their prognosis. However, the relationship between VDR polymorphisms and these two specific cancers remains a controversial hypothesis, and consequently needs further confirmation via clinical research together with genetic investigations. Here, we aimed to assess the correlation between the different alleles of VDR gene polymorphisms and renal cell cancer and breast cancer risks separately through a systematic review of the present literature. In contrast, this analysis has revealed that some VDR gene polymorphisms, such as: Bsm1, poly(A), Taq1, Apa1, are to some extent associated with breast cancer risk. Other polymorphisms were found to be significantly associated with renal cell cancer. Namely, they were Fok1, Bsm1, Taq1 and Apa1, which encode proteins participating mainly in proliferation, apoptosis and cell cycle regulation. However, data concerning renal cancer are not sufficient to firmly establish the VDR gene

  16. Association between ERCC5 gene polymorphisms and breast cancer risk.

    PubMed

    Na, Nari; Dun, Eer; Ren, Lidong; Li, Guoxin

    2015-01-01

    We conducted a case-control study to evaluate the association between ERCC5 polymorphism and breast cancer risk. 325 breast cancer patients and 325 controls were recruited in our study between January 2011 and March 2014. ERCC5 rs1047768, rs2094258, rs2296147, rs751402 and rs873601 polymorphisms were genotyped, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. By logistic regression analysis, we found that individuals with AA genotype of rs2094258 was associated with increased risk of breast cancer when compared with wide-type genotype, and the OR (95% CI) was 1.80 (1.12-2.92) for AA genotype. Individuals with GA+GG genotype of rs2094258 were significantly correlated with increased risk of breast cancer in tobacco smokers, and the OR (95% CI) was 7.35 (1.21-47.20). In conclusion, our study indicated that ERCC5 rs2094258 polymorphism may contribute to the risk of breast cancer. PMID:26045839

  17. Association between estrogen receptor alpha (ESR1) gene polymorphisms and severe preeclampsia.

    PubMed

    Molvarec, Attila; Vér, Agota; Fekete, Andrea; Rosta, Klára; Derzbach, László; Derzsy, Zoltán; Karádi, István; Rigó, János

    2007-03-01

    Associations have been reported between estrogen receptor alpha (ESR1) gene polymorphisms and various pathological conditions, including cardiovascular diseases. Our aim was to investigate whether two polymorphisms of the ESR1 gene (ESR1 c.454 -397T>C: PvuII restriction site and c.454 -351A>G: XbaI restriction site) are associated with preeclampsia. In a case-control study, we analyzed blood samples from 119 severely preeclamptic patients and 103 normotensive, healthy pregnant women using the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. All of the women were Caucasian. There was no association between severe preeclampsia and the PvuII and XbaI ESR1 gene polymorphisms separately. However, with the simultaneous carriage of both polymorphisms, the TT/AA genotype combination was significantly more frequent in severely preeclamptic patients than in healthy control subjects (24.4% vs. 9.7%, p=0.003), whereas the TT/AG combination was significantly less frequent in the severely preeclamptic group than in the control group (5.0% vs. 18.4%, p=0.002). According to the haplotype estimation, the homozygous T-A haplotype carriers had an increased risk of severe preeclampsia independent of maternal age, prepregnancy BMI, primiparity and smoking status (adjusted odds ratio [OR]: 4.36, 95% confidence interval [CI]: 1.65-11.53). The GG genotype of the XbaI polymorphism was associated with a lower risk of fetal growth restriction in patients with severe preeclampsia (OR: 0.23, 95% CI: 0.07-0.73). In conclusion, the homozygous T-A haplotype carriers of ESR1 PvuII and XbaI polymorphisms showed an increased risk of severe preeclampsia. In addition, the GG genotype of the XbaI polymorphism decreased the risk of fetal growth restriction in severely preeclamptic patients. PMID:17510501

  18. Polymorphisms and haplotypes in methylenetetrahydrofolate reductase gene and head and neck squamous cell carcinoma risk.

    PubMed

    Galbiatti, Ana Lívia Silva; Ruiz, Mariangela Torreglosa; Rodrigues, Juliana Olsen; Raposo, Luiz Sérgio; Maníglia, José Victor; Pavarino, Érika Cristina; Goloni-Bertollo, Eny Maria

    2012-01-01

    Functional polymorphisms in genes encoding enzymes involved in folate metabolism might modulate head and neck carcinoma risk because folate participates in DNA methylation and synthesis. We therefore conducted a case-control study of 853 individuals (322 head and neck cancer cases and 531 non-cancer controls) to investigate associations among MTHFR C677T and MTHFR A1298C polymorphisms and head and neck squamous cell carcinoma risk. Interactions between these two polymorphisms and risk factors and clinical histopathological parameters were also evaluated. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to genotype the polymorphisms and Chi-square test and multiple logistic regression were used for statistical analyses. The variables age≥49 years, male gender, tobacco habits and alcohol consumption, MTHFR 1298 AC or CC genotypes, combined genotypes with two or more polymorphic alleles and 677T and 1298C polymorphic alleles were associated with increased risk for this disease (P<0.05). Furthermore, we found that 1298 AC or CC genotypes were associated with age≥49 years, tobacco and alcohol habits (P<0.05). Regarding clinical histopathological parameters, the A1298C polymorphism was more frequent in patients with oral cavity as primary site (P<0.05). MTHFR polymorphisms may contribute for increase risk for head and neck carcinoma and the variables age≥49 years, male gender, tobacco and alcohol habits were associated with MTHFR 1298AC or CC genotypes, confirming that individuals with these variables and MTHFR A1298C polymorphism has higher risk for this disease. PMID:21556759

  19. Lack of association of the M129V polymorphism of the PRNP gene with pseudoexfoliation syndrome

    PubMed Central

    Giannakopoulos, Marios P; Antonacopoulou, Anna G; Kottorou, Anastasia E; Kalofonos, Haralabos P; Gartaganis, Sotirios P

    2016-01-01

    Purpose In this study we aimed to evaluate the polymorphism at codon 129 (M129V) of the PRNP gene as a secondary risk factor for pseudoexfoliation syndrome (PEX). Methods Two hundred and seventy-five unrelated subjects, including 156 patients with PEX and 119 unrelated control subjects, were recruited from the University Hospital of Patras, Greece. All patients and controls were of Caucasian or European ancestry. The PRNP M129V (A/G) single-nucleotide polymorphism was genotyped by real-time polymerase chain reactions. Association of the polymorphism with PEX was assessed using the two-sided Pearson’s chi-squared or Fisher’s exact test. Result No significant difference between patients and controls was observed in terms of frequencies of alleles and genotypes of the PRNP gene. Conclusion Polymorphism at M129V of the PRNP gene was evaluated as a secondary risk factor for developing PEX. Our results suggest that this PRNP gene polymorphism is not associated with PEX. PMID:27217717

  20. [Association of TNF-alpha and IL-13 genes polymorphisms with bronchial asthma].

    PubMed

    Liang, Wenhua; Zhou, Zhaoshan; Ji, Zhongqiang; Wang, Yanqing; Xue, Weilin; Zhang, Xiaoyan

    2015-10-01

    OBJECTIVE To assess the association of polymorphisms of TNF-alpha gene (rs1799724, rs1800630, rs1799964 and rs769178) and IL-13 gene (rs2158177 and rs1295687) with susceptibility to asthma among ethnic Chinese in Qingdao region. METHODS For 400 asthma patients and 200 healthy subjects, above polymorphisms were detected with a SNaPshot method. RESULTS For rs2158177, the frequency of genotype of GG in the asthma group was significantly lower than the control group (2.8% vs. 5%, OR = 0.31, 95%CI: 0.12-0.82, P = 0.021). No significant difference was detected in the genotypic frequencies for the remaining 5 polymorphisms between the two groups (All P > 0.05). CONCLUSION The study has indicated that rs2158177 polymorphism of the IL-13 gene is associated with asthma in ethnic Han Chinese from Qingdao. No association has been found between polymorphisms of TNF-alpha gene with susceptibility to asthma. PMID:26418997

  1. No Association between Personality and Candidate Gene Polymorphisms in a Wild Bird Population

    PubMed Central

    Durieux, Gillian; Burke, Terry; Dugdale, Hannah L.

    2015-01-01

    Consistency of between-individual differences in behaviour or personality is a phenomenon in populations that can have ecological consequences and evolutionary potential. One way that behaviour can evolve is to have a genetic basis. Identifying the molecular genetic basis of personality could therefore provide insight into how and why such variation is maintained, particularly in natural populations. Previously identified candidate genes for personality in birds include the dopamine receptor D4 (DRD4), and serotonin transporter (SERT). Studies of wild bird populations have shown that exploratory and bold behaviours are associated with polymorphisms in both DRD4 and SERT. Here we tested for polymorphisms in DRD4 and SERT in the Seychelles warbler (Acrocephalus sechellensis) population on Cousin Island, Seychelles, and then investigated correlations between personality and polymorphisms in these genes. We found no genetic variation in DRD4, but identified four polymorphisms in SERT that clustered into five haplotypes. There was no correlation between bold or exploratory behaviours and SERT polymorphisms/haplotypes. The null result was not due to lack of power, and indicates that there was no association between these behaviours and variation in the candidate genes tested in this population. These null findings provide important data to facilitate representative future meta-analyses on candidate personality genes. PMID:26473495

  2. Role of IL-10 gene polymorphisms in the development of acute pancreatitis.

    PubMed

    Jiang, B Z; Tang, L; Xue, H; Liu, D P

    2016-01-01

    Recent studies have suggested that chemokines contribute to the initiation and development of acute pancreatitis. We evaluated the relationship between IL-10 gene polymorphisms (-1082A/G and -819T/C) and development of acute pancreatitis in the Chinese population, in order to provide data for screening high-risk Chinese individuals. In total, 182 patients with confirmed cases of acute pancreatitis and 262 control subjects were recruited from the Shaanxi Provincial People's Hospital between April 2012 and December 2014. IL-10 gene polymorphisms at positions -1082A/G and -819T/C were examined using the polymerase chain reaction-restriction fragment length polymorphism method. Through multiple-logistic regression analysis, the GG genotype in IL-10 -1082A/G could influence the susceptibility to acute pancreatitis compared to the AA genotype, and the adjusted OR (95%CI) was 2.68 (1.34-5.39) (P = 0.002). Individuals who carried the AG+GG genotype of IL-10 -1082A/G were associated with greater risk for acute pancreatitis compared to the wide-type genotype, and the adjusted OR (95%CI) was 1.64 (1.09-2.46). However, no significant difference in susceptibility to acute pancreatitis was found between the IL-10 gene polymorphism at -819T/C. In conclusion, this study demonstrates that the IL-10 -1082A/G gene polymorphism contributes to the development of acute pancreatitis. PMID:27173345

  3. Genetic Polymorphisms of the Bovine NOV Gene Are Significantly Associated with Carcass Traits in Korean Cattle

    PubMed Central

    Kim, B. S.; Kim, S. C.; Park, C. M.; Lee, S. H.; Cho, S. H.; Kim, N. K.; Jang, G. W.; Yoon, D. H.; Yang, B. S.; Hong, S. K.; Seong, H. H.; Choi, B. H.

    2013-01-01

    The objective of this study was to investigate single nucleotide polymorphisms (SNPs) in the bovine nephroblastoma overexpressed (NOV) gene and to evaluate whether these polymorphisms affect carcass traits in the Korean cattle population. We resequenced to detect SNPs from 24 unrelated individuals and identified 19 SNPs within the full 8.4-kb gene, including the 1.5-kb promoter region. Of these 19 SNPs, four were selected for genotyping based on linkage disequilibrium (LD). We genotyped 429 steers to assess the associations of these four SNPs with carcass traits. Statistical analysis revealed that g.7801T>C and g.8379A>C polymorphisms in the NOV gene were associated with carcass weight (p = 0.012 and 0.008, respectively), and the g.2005A>G polymorphism was associated with the back fat thickness (BF) trait (p = 0.0001). One haplotype of the four SNPs (GGTA) was significantly associated with BF (p = 0.0005). Our findings suggest that polymorphisms in the NOV gene may be among the important genetic factors affecting carcass yield in beef cattle. PMID:25049850

  4. Tissue Factor Pathway Inhibitor-2 Gene Polymorphisms Associate With Coronary Atherosclerosis in Chinese Population

    PubMed Central

    Yu, Jia; Liu, Rong-Le; Luo, Xin-Ping; Shi, Hai-ming; Ma, Duan; Pan, Jun-Jie; Ni, Huan-Chun

    2015-01-01

    Abstract Tissue factor pathway inhibitor-2 (TFPI-2) may play critical roles in the pathogenesis of atherosclerosis. In this study, we aimed to investigate the association between TFPI-2 gene polymorphisms and coronary atherosclerosis. Four hundred and seven patients with coronary atherosclerosis and 306 individuals with normal coronary artery were enrolled in the present study. Nine single-nucleotide polymorphisms (SNPs) (rs3763473, rs59805398, rs60215632, rs59999573, rs59740167, rs34489123, rs4517, rs4264, and rs4271) were detected with polymerase chain reaction-direct sequencing method. Severity of coronary atherosclerosis was assessed by Gensini score. After the baseline investigation, patients with coronary atherosclerosis were followed up for incidence of cardiovascular events (CVEs). Eight SNPs were in accordance with the Hardy–Weinberg equilibrium, and 8 haplotypes were constructed based on rs59999573, rs59740167, and rs34489123 after linkage disequilibrium and haplotype analysis. Two SNPs (rs59805398 and rs34489123) and 5 haplotypes correlated with coronary atherosclerosis even after adjustment by Gensini score. At follow-up (median 53 months, range 1–60 months), 85 patients experienced CVE. However, there was no strong association between the gene polymorphisms and the occurrence of CVE. Tissue factor pathway inhibitor-2 gene polymorphisms were associated with coronary atherosclerosis in the Chinese population, suggesting that the information about TFPI-2 gene polymorphisms was useful for assessing the risk of developing coronary atherosclerosis, but there was not enough evidence showing it could predict occurrence of CVE. PMID:26496276

  5. Association analysis of the LTA4H gene polymorphisms and pulmonary tuberculosis in 9115 subjects

    PubMed Central

    Curtis, James; Kopanitsa, Liliya; Stebbings, Emma; Speirs, Arran; Ignatyeva, Olga; Balabanova, Yanina; Nikolayevskyy, Vladyslav; Hoffner, Sven; Horstmann, Rolf; Drobniewski, Francis; Nejentsev, Sergey

    2011-01-01

    Summary Immunoregulatory eicosanoids have been implicated in protection from mycobacterial infection in cell and animal models. Recently, a study of the zebrafish embryo demonstrated that mutants of the lta4h gene, which encodes the leukotriene A4 hydrolase (LTA4H) enzyme of the eicosanoid pathway, have hypersusceptibility to Mycobacterium marinum infection. It also reported that heterozygosity at the two single nucleotide polymorphisms rs1978331 and rs2660898 located in introns of the LTA4H gene, a human homologue of lta4h, is associated with protection from pulmonary tuberculosis. To replicate this association we genotyped six LTA4H gene polymorphisms in samples from 3703 pulmonary tuberculosis patients and 5412 healthy controls collected in Russia. We found no evidence of the protective effect of heterozygosity at the polymorphisms rs1978331 and rs2660898 (P = 0.29 and 0.49) and no association of the alleles of any of the six polymorphisms (P = 0.13–0.81). These results suggest that common polymorphisms in the LTA4H gene do not play any major role in susceptibility to clinical pulmonary tuberculosis. PMID:21112816

  6. Relevance between HLA-DP gene rs2281388 polymorphism and hepatocellular carcinoma risk

    PubMed Central

    Liu, Fangfeng; Wang, Jianlu; Chang, Hong; Lu, Jun; Li, Hongguang

    2015-01-01

    Purpose: We carried out this study to find out the relevance between rs2281388 T/C polymorphism of human leukocyte antigen (HLA) gene and hepatocellular carcinoma (HCC) risk in Chinese Han population. Methods: The method of polymerase chain reaction (PCR) was applied to amplify the genomic DNA. Then the PCR products were sequenced to test the HLA-DP gene rs2281388T/C polymorphism of the case and control groups. Odds ratios (ORs) and 95% confidence interval (95% CIs) were utilized to evaluate the potential correlation between rs2281388 variants and HCC risk. Results: We analyzed the rs2281388 polymorphism distribution among the clinical pathological features. The results showed that there existed a significant statistic correlation between rs2281388T/C polymorphism of HLA-DP gene and HBsAg feature, and no significant correlation was found between rs2281388 and other clinical features. Further analysis showed that the TT genotype of rs2281388 was significantly correlated with HCC risk, and the same to T allele, but there was no significant difference of CT genotype distribution in case and control groups. Conclusion: TT genotype and T allele of HLA-DP gene rs2281388 polymorphism may increase the risk of HCC. PMID:26261648

  7. DNA Repair Gene Polymorphism and the Risk of Mitral Chordae Tendineae Rupture

    PubMed Central

    Kalayci Yigin, Aysel; Bulent Vatan, Mehmet; Akdemir, Ramazan; Necati Murat Aksoy, Muhammed; Cakar, Mehmet Akif; Kilic, Harun; Erkorkmaz, Unal; Karacan, Keziban; Kaleli, Suleyman

    2015-01-01

    Polymorphisms in Lys939Gln XPC gene may diminish DNA repair capacity, eventually increasing the risk of carcinogenesis. The aim of the present study was to evaluate the significance of polymorphism Lys939Gln in XPC gene in patients with mitral chordae tendinea rupture (MCTR). Twenty-one patients with MCTR and thirty-seven age and sex matched controls were enrolled in the study. Genotyping of XPC gene Lys939Gln polymorphism was carried out using polymerase chain reaction- (PCR-) restriction fragment length polymorphism (RFLP). The frequencies of the heterozygote genotype (Lys/Gln-AC) and homozygote genotype (Gln/Gln-CC) were significantly different in MCTR as compared to control group, respectively (52.4% versus 43.2%, p = 0.049; 38.15% versus 16.2%, p = 0.018). Homozygote variant (Gln/Gln) genotype was significantly associated with increased risk of MCTR (OR = 2.059; 95% CI: 1.097–3.863; p = 0.018). Heterozygote variant (Lys/Gln) genotype was also highly significantly associated with increased risk of MCTR (OR = 1.489; 95% CI: 1.041–2.129; p = 0.049). The variant allele C was found to be significantly associated with MCTR (OR = 1.481; 95% CI: 1.101–1.992; p = 0.011). This study has demonstrated the association of XPC gene Lys939Gln polymorphism with MCTR, which is significantly associated with increased risk of MCTR. PMID:26604426

  8. PERB11 (MIC): a polymorphic MHC gene is expressed in skin and single nucleotide polymorphisms are associated with psoriasis

    PubMed Central

    Tay, G K; Hui, J; Gaudieri, S; Schmitt-Egenolf, M; Martinez, O P; Leelayuwat, C; Williamson, J F; Eiermann, T H; Dawkins, R L

    2000-01-01

    The susceptibility genes for psoriasis remain to be identified. At least one of these must be in the major histocompatibility complex (MHC) to explain associations with alleles at human leucocyte antigen (HLA)-A, -B, -C, -DR, -DQ and C4. In fact, most of these alleles are components of just two ancestral haplotypes (AHs) designated 13.1 and 57.1. Although relevant MHC gene(s) could be within a region of at least 4 Mb, most studies have favoured the area near HLA-B and -C. This region contains a large number of non-HLA genes, many of which are duplicated and polymorphic. Members of one such gene family, PERB11.1 and PERB11.2, are expressed in the skin and are encoded in the region between tumour necrosis factor and HLA-B. To investigate the relationship of PERB11.1 alleles to psoriasis, sequence based typing was performed on 97 patients classified according to age of onset and family history. The frequency of the PERB11.1*06 allele is 44% in type I psoriasis but only 7% in controls (Pc = 0.003 by Fisher's exact test, two-tailed). The major determinant of this association is a single nucleotide polymorphism (SNP) within intron 4. In normal and affected skin, expression of PERB11 is mainly in the basal layer of the epidermis including ducts and follicles. PERB11 is also present in the upper keratin layers but there is relative deficiency in the intermediate layers. These findings suggest a possible role for PERB11 and other MHC genes in the pathogenesis of psoriasis. PMID:10691930

  9. Relationship among maternal blood lead, ALAD gene polymorphism and neonatal neurobehavioral development

    PubMed Central

    Yun, Li; Zhang, Weixing; Qin, Kejun

    2015-01-01

    Lead is a widely used heavy metal that can affect children’s nervous system development. ALAD gene polymorphism is associated with lead neurotoxicity. This study aimed to clarify the relationship among maternal blood lead, ALAD gene polymorphism, and neonatal neurobehavioral development through detecting maternal blood lead and ALAD gene polymorphism. 198 maternal and neonatal were selected as the research object. Graphite furnace atomic absorption method was applied to detect the maternal blood lead concentration. PCR-RFLP was used to detect ALAD genotype distribution. Neonatal NANB score was treated as effect indicator. SPSS was used for statistical analysis. The ALAD genotype was 181 cases (91.4%) for ALAD11 and 17 cases (8.6%) for ALAD12. ALAD allele frequency distribution accords with genetics Hardy-Weinberg balance (P > 0.05). Blood lead level in maternal with ALAD12 genotype was significantly higher than with ALAD11 genotype (P < 0.01). NANB score in high blood lead neonatal group was obviously lower than the low blood lead group (P < 0.05). Newborn’s NANB score from the maternal with ALAD11 genotype was lower than from the maternal with ALAD12 genotype (P < 0.01). After ruling out the confounding factors influence by multiple linear regressions, ALAD gene polymorphisms had no significant correlation with neonatal NANB score (P > 0.05). ALAD gene polymorphism is associated with the blood lead level. Low level lead exposure in utero may cause newborn early neurobehavioral maldevelopment. Maternal ALAD gene polymorphism can affect early neonatal neurobehavioral development by influencing the blood lead level. PMID:26261627

  10. Genetic polymorphism in three glutathione s-transferase genes and breast cancer risk

    SciTech Connect

    Woldegiorgis, S.; Ahmed, R.C.; Zhen, Y.; Erdmann, C.A.; Russell, M.L.; Goth-Goldstein, R.

    2002-04-01

    The role of the glutathione S-transferase (GST) enzyme family is to detoxify environmental toxins and carcinogens and to protect organisms from their adverse effects, including cancer. The genes GSTM1, GSTP1, and GSTT1 code for three GSTs involved in the detoxification of carcinogens, such as polycyclic aromatic hydrocarbons (PAHs) and benzene. In humans, GSTM1 is deleted in about 50% of the population, GSTT1 is absent in about 20%, whereas the GSTP1 gene has a single base polymorphism resulting in an enzyme with reduced activity. Epidemiological studies indicate that GST polymorphisms increase the level of carcinogen-induced DNA damage and several studies have found a correlation of polymorphisms in one of the GST genes and an increased risk for certain cancers. We examined the role of polymorphisms in genes coding for these three GST enzymes in breast cancer. A breast tissue collection consisting of specimens of breast cancer patients and non-cancer controls was analyzed by polymerase chain reaction (PCR) for the presence or absence of the GSTM1 and GSTT1 genes and for GSTP1 single base polymorphism by PCR/RFLP. We found that GSTM1 and GSTT1 deletions occurred more frequently in cases than in controls, and GSTP1 polymorphism was more frequent in controls. The effective detoxifier (putative low-risk) genotype (defined as presence of both GSTM1 and GSTT1 genes and GSTP1 wild type) was less frequent in cases than controls (16% vs. 23%, respectively). The poor detoxifier (putative high-risk) genotype was more frequent in cases than controls. However, the sample size of this study was too small to provide conclusive results.

  11. Effect of BDKRB2 Gene -9/+9 Polymorphism on Training Improvements in Competitive Swimmers.

    PubMed

    Zmijewski, Piotr; Grenda, Agata; Leońska-Duniec, Agata; Ahmetov, Ildus; Orysiak, Joanna; Cięszczyk, Pawel

    2016-03-01

    The aim of the study was to investigate the possible association between the BDKRB2 gene and training-induced improvements in swimming performance in well-trained swimmers. One hundred Polish swimmers (52 men and 48 women, aged 18.1 ± 1.9 years), who competed in national and international competitions at middle- (200 m) and long-distance events (≥400 m), were included in the study. Athletes' genotype and allele distributions were analyzed in comparison to 230 unrelated sedentary subjects, who served as controls, with the χ test. All samples were genotyped for the BDKRB2 -9/+9 polymorphism by polymerase chain reaction. The effects of genotype on swimming performance improvements were analyzed with two-way (3 × 2; genotype × time) analysis of variance with metric age as a covariate. The training period of 1.9 ± 0.4 years had a significant (p < 0.01) effect on swimming performance, both in female and male athletes. Both in female and male athletes, the BDKRB2 gene -9/+9 polymorphism had no significant effect on swimming performance. An interaction effect of BDKRB2 gene -9/+9 polymorphism × time was found for swimming performance only in male athletes. Post hoc analyses showed that swimmers with the +9/+9 BDKRB2 genotype had a greater improvement in swimming performance than swimmers with the -9/+9 polymorphism (p ≤ 0.05). No interaction effects for gender × BDKRB2 gene -9/+9 polymorphism were found for either swimming performance or improvement in swimming performance. These results suggest that the response to long-term exercise training could be modulated by the BDKRB2 gene -9/+9 polymorphism in male athletes. In well-trained swimmers, BDKRB2 gene variation was not found to be an independent determinant of swimming performance. PMID:26907838

  12. Genetic polymorphism of toll-like receptors 4 gene by polymerase chain reaction-restriction fragment length polymorphisms, polymerase chain reaction-single-strand conformational polymorphism to correlate with mastitic cows

    PubMed Central

    Gupta, Pooja H.; Patel, Nirmal A.; Rank, D. N.; Joshi, C. G.

    2015-01-01

    Aim: An attempt has been made to study the toll-like receptors 4 (TLR4) gene polymorphism from cattle DNA to correlate with mastitis cows. Materials and Methods: In present investigation, two fragments of TLR4 gene named T4CRBR1 and T4CRBR2 of a 316 bp and 382 bp were amplified by polymerase chain reaction (PCR), respectively from Kankrej (22) and Triple cross (24) cattle. The genetic polymorphisms in the two populations were detected by a single-strand conformational polymorphism in the first locus and by digesting the fragments with restriction endonuclease Alu I in the second one. Results: Results showed that both alleles (A and B) of two loci were found in all the two populations and the value of polymorphism information content indicated that these were highly polymorphic. Statistical results of χ2 test indicated that two polymorphism sites in the two populations fit with Hardy–Weinberg equilibrium (p<0.05). Meanwhile, the effect of polymorphism of TLR4 gene on the somatic cell score (SCS) indicated the cattle with allele a in T4CRBR1 showed lower SCS than that of allele B (p<0.05). Thus, the allele A might play an important role in mastitis resistance in cows. Conclusion: The relationship between the bovine mastitis trait and the polymorphism of TLR4 gene indicated that the bovine TLR4 gene may play an important role in mastitis resistance. PMID:27047144

  13. The Relationship Between Gene Polymorphism of Leptin and Leptin Receptor and Growth Hormone Deficiency.

    PubMed

    He, Jinshui; Fang, Yanling; Lin, Xinfu; Zhou, Huowang; Zhu, Shaobo; Zhang, Yugui; Yang, Huicong; Ye, Xiaoling

    2016-01-01

    BACKGROUND Growth hormone deficiency (GHD) is a major cause of congenital short stature. GHD patients have significantly decreased serum leptin levels, which are regulated by gene polymorphism of leptin and leptin receptor. This study thus investigated the relationship between gene polymorphism and susceptibility to GHD. MATERIAL AND METHODS A case-control study was performed using 180 GHD children in addition to 160 healthy controls. After the extraction of whole genomic DNA, the genotypes of leptin and leptin receptor gene loci were analyzed by sequencing for single-nucleotide polymorphism. RESULTS The frequency distribution of all alleles identified in leptin gene (loci rs7799039) and leptin receptor gene (loci rs1137100 and rs1137101) fit Hardy-Weinberg equilibrium. There was a significant difference in allele frequency at loci rs7799039 or rs1137101, as individuals with heterozygous GA allele had lower (rs7799039) or higher (rs1137101) GHD risk. No significant difference in allele frequency was discovered at loci rs1137100 (p>0.05), which was unrelated to GHD susceptibility. CONCLUSIONS Gene polymorphism of leptin (loci rs7799039) and leptin receptor (loci rs1137101) are correlated with GHD susceptibility. PMID:26915772

  14. The Relationship Between Gene Polymorphism of Leptin and Leptin Receptor and Growth Hormone Deficiency

    PubMed Central

    He, Jinshui; Fang, Yanling; Lin, Xinfu; Zhou, Huowang; Zhu, Shaobo; Zhang, Yugui; Yang, Huicong; Ye, Xiaoling

    2016-01-01

    Backgrounds Growth hormone deficiency (GHD) is a major cause of congenital short stature. GHD patients have significantly decreased serum leptin levels, which are regulated by gene polymorphism of leptin and leptin receptor. This study thus investigated the relationship between gene polymorphism and susceptibility to GHD. Material/Methods A case-control study was performed using 180 GHD children in addition to 160 healthy controls. After the extraction of whole genomic DNA, the genotypes of leptin and leptin receptor gene loci were analyzed by sequencing for single-nucleotide polymorphism. Results The frequency distribution of all alleles identified in leptin gene (loci rs7799039) and leptin receptor gene (loci rs1137100 and rs1137101) fit Hardy-Weinberg equilibrium. There was a significant difference in allele frequency at loci rs7799039 or rs1137101, as individuals with heterozygous GA allele had lower (rs7799039) or higher (rs1137101) GHD risk. No significant difference in allele frequency was discovered at loci rs1137100 (p>0.05), which was unrelated to GHD susceptibility. Conclusions Gene polymorphism of leptin (loci rs7799039) and leptin receptor (loci rs1137101) are correlated with GHD susceptibility. PMID:26915772

  15. Haplotype Analysis of Hemochromatosis Gene Polymorphisms in Chronic Hepatitis C Virus Infection: A Case Control Study

    PubMed Central

    Gerayli, Sina; Pasdar, Alireza; Shakeri, Mohammad Taghi; Sepahi, Samaneh; Hoseini, Seyed Mousalreza; Ahadi, Mitra; Rostami, Sina; Meshkat, Zahra

    2016-01-01

    Background Chronic hepatitis C virus (HCV) infection is frequently associated with elevated serum iron markers. Polymorphisms in the hemochromatosis (HFE) genes are responsible for iron accumulation in most cases of hemochromatosis, and may play a role in HCV infection. Objectives We aimed to assess the prevalence of HFE gene polymorphisms in a group of Iranian HCV-infected patients, and to explore the association of these polymorphisms with HCV infection. Patients and Methods HFE gene polymorphisms were examined in a total of 69 HCV patients and 69 healthy controls using polymerase chain reaction and restriction fragment length polymorphism techniques. Haplotype and diplotype analyses were performed using PHASE software. Results In a recessive analysis model of the His63Asp (H63D) locus (HH vs. HD + DD), the HH genotype was more common in patients compared to controls (adjusted P = 0.012; OR = 6.42 [95% CI: 1.51 - 27.33]). Also, in a recessive analysis model of the Cys282Tyr (C282Y) locus (CC vs. CY + YY), the CC genotype was more frequent in patients compared to controls (adjusted P = 0.03; OR = 5.06 [95% CI: 1.13 - 22.06]). In addition, there was a significant association between the HC haplotype and the HCDC diplotype and HCV infection. Conclusions Polymorphism in the hemochromatosis gene may confer some degree of risk for HCV infection, and individuals carrying the H and C alleles may be susceptible to this disease; however, a larger sample of HCV patients and healthy individuals may be necessary to further illustrate the role of these polymorphisms in HCV. PMID:27621921

  16. Combination of Thrombophilic Gene Polymorphisms as a Cause of Increased the Risk of Recurrent Pregnancy Loss

    PubMed Central

    Torabi, Raheleh; Zarei, Saeed; Zeraati, Hojjat; Zarnani, Amir Hassan; Akhondi, Mohammad Mehdi; Hadavi, Reza; Shiraz, Elham Savadi; Jeddi-Tehrani, Mahmood

    2012-01-01

    Background Recurrent pregnancy loss is (RPL) a heterogeneous condition. While the role of acquired thrombophilia has been accepted as an etiology for RPL, the contribution of specific inherited thrombophilic gene polymorphisms to the disorder has been remained controversial. Methods One hundred women with a history of two or more consecutive abortions and 100 women with at least two live births and no miscarriages were included in the study and evaluated for the presence of 11 thrombophilic gene polymorphisms (Factor V LEIDEN, Factor V 4070 A/G, Factor V 5279 A/G, Factor XIII 103 G/T, Factor XIII 614 A/T, Factor XIII 1694 C/T, PAI-1 -675 4G/5G, ITGB3 1565 T/C, β-Fibrinogen -455G/A, MTHFR 677 C/T, MTHFR 1298 A/C) using PCR-RFLP technique. The data were statistically analyzed using Mann-Whitney test and logistic regression model. Results There was no relation between factor XIII 103G/T gene polymorphism with increased risk of RPL. However, the other 10 gene polymorphisms were found to be associated with increased/decreased risk of RPL. Multiple logistic regression model for analyzing the simultaneous effects of these polymorphisms on the risk of RPL showed that six of these 11 polymorphisms (Factor V 1691G/A, Factor V 5279A/G, Factor XIII 614A/T, β-Fibrinogen -455G/A, ITGB3 1565T/C, and MTHFR 1298A/ C) were associated with RPL. Conclusion It is possible to calculate the risk of abortion in a patient with RPL by determining only six of the 10 polymorphisms that are individually associated with RPL. PMID:23926530

  17. The human XPG gene: gene architecture, alternative splicing and single nucleotide polymorphisms

    PubMed Central

    Emmert, Steffen; Schneider, Thomas D.; Khan, Sikandar G.; Kraemer, Kenneth H.

    2001-01-01

    Defects in the XPG DNA repair endonuclease gene can result in the cancer-prone disorders xeroderma pigmentosum (XP) or the XP–Cockayne syndrome complex. While the XPG cDNA sequence was known, determination of the genomic sequence was required to understand its different functions. In cells from normal donors, we found that the genomic sequence of the human XPG gene spans 30 kb, contains 15 exons that range from 61 to 1074 bp and 14 introns that range from 250 to 5763 bp. Analysis of the splice donor and acceptor sites using an information theory-based approach revealed three splice sites with low information content, which are components of the minor (U12) spliceosome. We identified six alternatively spliced XPG mRNA isoforms in cells from normal donors and from XPG patients: partial deletion of exon 8, partial retention of intron 8, two with alternative exons (in introns 1 and 6) and two that retained complete introns (introns 3 and 9). The amount of alternatively spliced XPG mRNA isoforms varied in different tissues. Most alternative splice donor and acceptor sites had a relatively high information content, but one has the U12 spliceosome sequence. A single nucleotide polymorphism has allele frequencies of 0.74 for 3507G and 0.26 for 3507C in 91 donors. The human XPG gene contains multiple splice sites with low information content in association with multiple alternatively spliced isoforms of XPG mRNA. PMID:11266544

  18. Discovery of nucleotide polymorphisms in the Musa gene pool by Ecotilling.

    PubMed

    Till, Bradley J; Jankowicz-Cieslak, Joanna; Sági, László; Huynh, Owen A; Utsushi, Hiroe; Swennen, Rony; Terauchi, Ryohei; Mba, Chikelu

    2010-11-01

    Musa (banana and plantain) is an important genus for the global export market and in local markets where it provides staple food for approximately 400 million people. Hybridization and polyploidization of several (sub)species, combined with vegetative propagation and human selection have produced a complex genetic history. We describe the application of the Ecotilling method for the discovery and characterization of nucleotide polymorphisms in diploid and polyploid accessions of Musa. We discovered over 800 novel alleles in 80 accessions. Sequencing and band evaluation shows Ecotilling to be a robust and accurate platform for the discovery of polymorphisms in homologous and homeologous gene targets. In the process of validating the method, we identified two single nucleotide polymorphisms that may be deleterious for the function of a gene putatively important for phototropism. Evaluation of heterozygous polymorphism and haplotype blocks revealed a high level of nucleotide diversity in Musa accessions. We further applied a strategy for the simultaneous discovery of heterozygous and homozygous polymorphisms in diploid accessions to rapidly evaluate nucleotide diversity in accessions of the same genome type. This strategy can be used to develop hypotheses for inheritance patterns of nucleotide polymorphisms within and between genome types. We conclude that Ecotilling is suitable for diversity studies in Musa, that it can be considered for functional genomics studies and as tool in selecting germplasm for traditional and mutation breeding approaches. PMID:20589365

  19. Polymorphisms of the sigma(1) receptor gene in schizophrenia: An association study.

    PubMed

    Ohmori, O; Shinkai, T; Suzuki, T; Okano, C; Kojima, H; Terao, T; Nakamura, J

    2000-02-01

    Possible involvement of sigma receptors in the pathogenesis of schizophrenia has been suggested. In this study we searched systematically for polymorphisms in the 5'-franking region of the sigma(1) receptor. Genetic variation in this region could reduce the expression of the gene, and this suggestion is compatible with findings of reduced sigma binding sites in several cortical regions of schizophrenia. We confirmed G-241T and G-240T polymorphisms; these two consecutive polymorphisms were resolved to be in complete linkage disequilibrium with each other by single-strand conformation polymorphism (SSCP) analysis. We also identified the A61C (Gln2Pro) polymorphism, which was in almost complete linkage disequilibrium with G-241T/G-240T. There was no significant difference in the distribution of alleles or overall genotypes of the polymorphisms between schizophrenic patients (n = 129) and controls (n = 140). We found slight increased homozygosity for T-241/T-240 and C61 in patients compared with controls using multiple comparison (p = 0. 045). However, the significance did not remain when a Bonferroni correction was made (p = 0.135). These results do not support that the sigma(1) receptor gene plays a major role in the pathogenesis of schizophrenia. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:118-122, 2000. PMID:10686564

  20. LEPR, ADBR3, IRS-1 and 5-HTT genes polymorphisms do not associate with obesity.

    PubMed

    Mergen, Hatice; Karaaslan, Cağatay; Mergen, Mehmet; Deniz Ozsoy, Ergi; Ozata, Metin

    2007-02-01

    Obesity is a growing problem and is associated with numerous medical conditions. In several genes coding for molecules involved in the regulation of body weight (fat mass) and thermogenesis, polymorphisms have been reported which possibly modify human obesity risk. The aim of this study was to determine the incidence of the following polymorphisms in the following genes in 262 obese (BMI > or = 30) and 138 control (BMI < or = 25) subjects: leptin receptor (LEPR)-Gln223Arg, B3-adrenergic receptor (B3-AR)-Trp64Arg, serotonin transporter (5-HTT)--a 44-base pair insertion/deletion functional polymorphism in the 5-HTTLPR and insulin receptor substrate-1 (IRS-1)-Gly972Arg. Our hypothesis was that these polymorphisms would occur more frequently in the obese population. The polymorphisms were determined by polymerase chain reaction (PCR) and restriction genotyping in study population. In our results, no strong associations were observed between BMI status and these polymorphisms. Weak, though significant, association coefficients obtained with HTT and LEPR loci indicate that the genotype numbers at these loci may depend on BMI status to some extent. PMID:17124363

  1. [Intraspecific polymorphism of the sucrose synthase genes in Russian and Kazakhstan potato cultivars].

    PubMed

    Slugina, M A; Boris, K V; Kakimzhanova, A A; Kochieva, E Z

    2014-06-01

    In 12 different Russian and Kazakhstan potato cultivars, the polymorphism of the glycosyltransferase domain of the sucrose synthase gene was first examined, as well as the polymorphism of the sucrose synthase domain fragment of the same gene in the potato cultivars of Kazakhstan breed. It was demonstrated that the examined sequences contained point mutations, as well as insertions and deletions, including those not described earlier. Amino acid substitutions specific to heat- and drought-tolerant varieties were also identified and could be associated with the development of abiotic stress resistance. PMID:25715458

  2. Family-based study of brain-derived neurotrophic factor (BDNF) gene polymorphism in alcohol dependence.

    PubMed

    Grzywacz, Anna; Samochowiec, Agnieszka; Ciechanowicz, Andrzej; Samochowiec, Jerzy

    2010-01-01

    Brain-derived neurotrophic factor (BDNF) belongs to a family of proteins related to the nerve growth factor family, which are responsible for the proliferation, survival and differentiation of neurons. BDNF is thought to be involved in the pathogenesis of bipolar disorder, schizophrenia, eating disorders and addiction. We hypothesize that a functionally relevant polymorphism of the BDNF gene promoter may be associated with the pathogenesis of alcohol dependence. We performed an association study of 141 families with alcohol dependence. One hundred and thirty-eight healthy control subjects were matched based on ethnicity and gender. An association between the BDNF Val66Met gene polymorphism and alcoholism was not found. PMID:21098877

  3. Polymorphisms of the ELANE Gene Promoter Region in End-Stage Chronic Kidney Disease Patients

    PubMed Central

    Fernandes, Rafael; Freitas, Bruno; Miranda, Vasco; Costa, Elísio; Santos-Silva, Alice; Bronze-da-Rocha, Elsa

    2016-01-01

    End-stage renal disease (ESRD) patients have a high mortality rate that exceeds that of non-ESRD population. The hemodialysis procedure induces neutrophil activation and elastase release, which might have a role in the inflammatory process and in the development of oxidative stress. The ELANE gene encodes the neutrophil elastase. We analyzed the effect of ELANE promoter region polymorphisms and its relation with the circulating levels of elastase, as well as several clinical, biochemical and inflammatory markers in 123 ESRD patients. We found two duplications in heterozygosity in the promoter region and a new polymorphism, the c.-801G>A. ESRD patients heterozygous for the c.-903T>G polymorphism had no changes in the circulating levels of elastase or other evaluated variables, and those homozygous for the c.-741G>A polymorphism showed significant effects on neutrophils count, as well as in neutrophils/lymphocytes ratio, which might be associated with an increased inflammatory process. PMID:27136588

  4. [The C5 gene polymorphism in patients with PNH].

    PubMed

    Nishimura, Jun-Ichi; Kanakura, Yuzuru

    2015-02-01

    This review is a commentary on an article entitled "Genetic variants in C5 and poor response to eculizumab" (N Engl J Med. 2014; 370: 632-639). The molecular basis for the poor response to eculizumab in Japanese patients is unclear. Of 345 Japanese patients with paroxysmal nocturnal hemoglobinuria (PNH) who received eculizumab, 11 showed a poor response. All 11 had a single missense C5 heterozygous mutation, c.2654 G>A, which predicts the polymorphism p.Arg885His. The prevalence of this mutation among patients with PNH (3.2%) was similar to that in healthy Japanese persons (3.5%). This polymorphism was also identified in a Han Chinese population. Non-mutant and mutant C5 both caused hemolysis in vitro, but only non-mutant C5 bound to and was blocked by eculizumab. In vitro hemolysis due to non-mutant and mutant C5 was completely blocked by N19-8, a monoclonal antibody that binds to a different site on C5 than does eculizumab. The functional capacity of the C5 polymorphism p.Arg885His, together with its failure to undergo blockade by eculizumab, accounts for the poor response to this agent in patients who carry this mutation. PMID:25765788

  5. Microarray study of single nucleotide polymorphisms and expression of ATP-binding cassette genes in breast tumors

    NASA Astrophysics Data System (ADS)

    Tsyganov, M. M.; Ibragimova, M. K.; Karabut, I. V.; Freydin, M. B.; Choinzonov, E. L.; Litvyakov, N. V.

    2015-11-01

    Our previous research establishes that changes of expression of the ATP-binding cassette genes family is connected with the neoadjuvant chemotherapy effect. However, the mechanism of regulation of resistance gene expression remains unclear. As many researchers believe, single nucleotide polymorphisms can be involved in this process. Thereupon, microarray analysis is used to study polymorphisms in ATP-binding cassette genes. It is thus found that MDR gene expression is connected with 5 polymorphisms, i.e. rs241432, rs241429, rs241430, rs3784867, rs59409230, which participate in the regulation of expression of own genes.

  6. Pig fatness in relation to FASN and INSIG2 genes polymorphism and their transcript level.

    PubMed

    Grzes, Maria; Sadkowski, Slawomir; Rzewuska, Katarzyna; Szydlowski, Maciej; Switonski, Marek

    2016-05-01

    Fat content and fatty acid (FA) profile influence meat quality in pigs. These parameters are important for consumers due to their preferences for healthy, high quality meat. The aim of this study was searching for polymorphisms and transcript levels of two positional and functional candidate genes, FASN and INSIG2, encoding proteins which take part in lipid metabolism. The molecular findings were analyzed in relation to fatness traits. Pigs of four commercial breeds were included: Polish Landrace (PL), Polish Large White (PLW), Duroc and Pietrain. DNA sequencing, 5'RACE technique and real time PCR and association analysis were applied. In total, 20 polymorphisms in 5'-flanking, 5'UTR and 3'UTR regions of FASN (12 novel polymorphisms) and INSIG2 (seven novel ones and one known) genes were found. Association study with fatness traits (PL n = 225, PLW n = 179) revealed that four polymorphisms (c.-2908G>A, c.-2335C>T, c.*42_43insCCCCA and c.*264A>G) of the FASN gene were associated with back fat thickness in PL and PLW. Since the polymorphisms were identified in regulatory sequences of the both genes also their transcript levels were studied in PLW (n = 23), PL (n = 22), Pietrain (n = 17) and Duroc (n = 23). The INSIG2 transcript level was positively correlated with monounsaturated FA contents in the longissimus thoracis et lumborum muscle. Several correlations were also found between three polymorphisms (c.*264A>G and c.-2335C>T in FASN, and c.-5527C>G in INSIG2) and the FA content. Our study showed that the FASN gene is a promising marker for subcutaneous fat tissue accumulation, while INSIG2 is a promising marker for FA composition. PMID:26965892

  7. CREB1 gene polymorphisms combined with environmental risk factors increase susceptibility to major depressive disorder (MDD)

    PubMed Central

    Wang, Peng; Yang, Yanjie; Yang, Xiuxian; Qiu, Xiaohui; Qiao, Zhengxue; Wang, Lin; Zhu, Xiongzhao; Sui, Hong; Ma, Jingsong

    2015-01-01

    Major depressive disorder (MDD) is one of the most severe psychiatric disorders. The objective of this study was to explore the effects of CREB1 gene polymorphisms on risk of developing MDD and the joint effects of gene-environment interactions. Genotyping was performed by Taqman allelic discrimination assay among 586 patients and 586 healthy controls. A significant impact on rs6740584 genotype distribution was found for childhood trauma (P = 0.015). We did not find an association of CREB1 polymorphisms with MDD susceptibility. However, we found a significantly increased risk associated with the interactions of CREB1 polymorphisms and drinking (OR = 11.67, 95% CI = 2.52-54.18; OR = 11.52, 95% CI = 2.55-51.95 for rs11904814; OR = 4.18, 95% CI = 1.87-9.38; OR = 5.02, 95% CI = 2.27-11.14 for rs6740584; OR = 7.58, 95% CI = 2.05-27.98; OR = 7.59, 95% CI = 2.12-27.14 for rs2553206; OR = 8.37, 95% CI = 3.02-23.23; OR = 7.84, 95% CI = 2.93-20.98 for rs2551941). We also noted that CREB polymorphisms combined with family harmony and childhood trauma conferred increased susceptibility for MDD. In conclusion, polymorphisms in the CREB gene may not be independently associated with MDD risk, but they are likely to confer increased susceptibility by interacting with environmental risk factors in the Chinese population. PMID:25755794

  8. Association study between miR-149 gene polymorphism and nasopharyngeal carcinoma.

    PubMed

    Huang, Guo-Liang; Lu, Yan; Pu, Xing-Xiang; He, Yu-Xiang; Chen, Mei-Ling; Li, Ya-Zhen; Tang, Shu-Yin; Che, Hua; He, Zhiwei

    2013-07-01

    Association studies between single-nucleotide polymorphism (SNP) rs2292832 on miR-149 gene and cancer risk have been previously analyzed in several types of cancer. The aim of this study was to evaluate the association between miR-149 polymorphism and risk of nasopharyngeal carcinoma (NPC). miR-149 gene polymorphism was genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) in 158 patients with NPC and 242 healthy individuals. Associations with cancer risk and clinicopathological characteristics were analyzed by χ(2) test. No significant difference was observed for miR-149 gene polymorphism in NPC patients and healthy controls in either genotype (P=0.427 for CC vs. CT vs. TT, P=0.247 for CT vs. TT and P=0.323 for CC vs. TT, respectively) or allelic analysis (P=0.216). No significant difference was noted between the genotypes and the clinicopathological parameters examined with the exception of clinical stage. A significantly higher CC distribution in clinical stage I-II compared with III-IV was observed under the dominant model (CC vs. CT vs. TT, P=0.026) and the co-dominant model (CC vs. TT, P=0.030). The results of this study suggested that the CC genotype of miR-149 contributes to the progression and development, rather than the initiation of NPC. PMID:24648993

  9. New DNA polymorphisms define ethnically distinct haplotypes in the human transferrin receptor gene.

    PubMed

    Van Landeghem, G F; Beckman, L E; Sikström, C; Saha, N; Kucinskas, V; Beckman, L

    1998-01-01

    In a study of transferrin receptor (TFR) polymorphism in different ethnic groups using PCR and restriction cleavage we found a new Hin6I polymorphism in intron 7 and confirmed a tentative BanI polymorphism in exon 4 reported by Evans and Kemp [Gene 1997;199:123-131]. In all ethnic groups there was a complete and highly significant (p < 10(-10)) linkage disequilibrium where all BanI 1 alleles were linked to Hin6I 1 alleles. Furthermore in the European populations, but not in the Chinese, there was a close correlation between the three BanI-Hin6I haplotypes and the alleles of a previously described three-allelic RsaI polymorphism in the TFR gene studied by Southern blotting. There were distinct ethnic differences in TFR allele and haplotype frequencies. Thus the Saamis were significantly different from the other European ethnic groups, and the Lithuanians had a significantly increased frequency of the BanI 2-Hin6I 1 haplotype, suggesting that this marker may be informative in tracing prehistoric migrations and admixture by Baltic peoples. The new TFR polymorphisms and haplotypes may also be useful markers in studies of interactions with the transferrin and hemochromatosis genes, the genetic influence on body iron stores and disease associations. PMID:9748693

  10. Vitamin D Receptor Gene Polymorphism and the Risk of Multiple Sclerosis in South Eastern of Iran.

    PubMed

    Narooie-Nejad, Mehrnaz; Moossavi, Maryam; Torkamanzehi, Adam; Moghtaderi, Ali; Salimi, Saeedeh

    2015-07-01

    Multiple sclerosis is one of the most widespread demyelinating diseases of the central nervous system. Environmental and genetic factors are collaborating in triggering MS. The role of vitamin D receptor (VDR) gene and its polymorphisms are highlighted as susceptible components. The aim of the present study was to examine the association of single nucleotide polymorphism (SNP)-BsmI and FokI-in VDR gene and MS susceptibility in the South Eastern Iranian population. Therefore, 113 MS patients and 122 controls were recruited in the study. Restriction fragment length polymorphism was performed to detect the SNPs. There were no significant differences in the polymorphism of FokI (rs2228570) in VDR gene among patients and controls (P > 0.05), while a significant difference was observed in BsmI (rs1544410) polymorphism in healthy subjects and homozygous genotype-b/b- with MS (P = 0.025). Results showed a protective association of homozygous genotype-b/b- of BsmI with MS susceptibility in a population in South Eastern of Iran. PMID:25854779

  11. Toll-like receptor 3 gene polymorphisms in South African Blacks with type 1 diabetes.

    PubMed

    Pirie, F J; Pegoraro, R; Motala, A A; Rauff, S; Rom, L; Govender, T; Esterhuizen, T M

    2005-08-01

    Type 1 diabetes is the consequence of exposure of genetically susceptible individuals to specific environmental precipitants. The innate immune system provides the initial response to exogenous antigen and links with the adaptive immune system. The aim of this study was to assess the role of polymorphisms occurring in the cytoplasmic region of toll-like receptor (TLR) 3 gene and immediate 5' sequence, in subjects of Zulu descent with type 1 diabetes in KwaZulu-Natal, South Africa. Seventy-nine subjects with type 1 diabetes and 74 healthy normal glucose tolerant gender-matched control subjects were studied. Parts of exon 4 and exon 3/intron 3 of the TLR3 gene were studied by polymerase chain reaction, direct sequencing and restriction enzyme digestion with Bts 1. Of the nine polymorphisms studied, a significant association with type 1 diabetes was found for the major allele in the 2593 C/T polymorphism and for the minor alleles in the 2642 C/A and 2690 A/G polymorphisms, which were found to be in complete linkage disequilibrium. Correction of the P-values for the number of alleles studied, however, rendered the results no longer significant. These results suggest that polymorphisms in the TLR3 gene, which is part of the innate immune system, may be associated with type 1 diabetes in this population. PMID:16029432

  12. Clock gene polymorphism and scheduling of migration: a geolocator study of the barn swallow Hirundo rustica

    PubMed Central

    Bazzi, Gaia; Ambrosini, Roberto; Caprioli, Manuela; Costanzo, Alessandra; Liechti, Felix; Gatti, Emanuele; Gianfranceschi, Luca; Podofillini, Stefano; Romano, Andrea; Romano, Maria; Scandolara, Chiara; Saino, Nicola; Rubolini, Diego

    2015-01-01

    Circannual rhythms often rely on endogenous seasonal photoperiodic timers involving ‘clock’ genes, and Clock gene polymorphism has been associated to variation in phenology in some bird species. In the long-distance migratory barn swallow Hirundo rustica, individuals bearing the rare Clock allele with the largest number of C-terminal polyglutamine repeats found in this species (Q8) show a delayed reproduction and moult later. We explored the association between Clock polymorphism and migration scheduling, as gauged by light-level geolocators, in two barn swallow populations (Switzerland; Po Plain, Italy). Genetic polymorphism was low: 91% of the 64 individuals tracked year-round were Q7/Q7 homozygotes. We compared the phenology of the rare genotypes with the phenotypic distribution of Q7/Q7 homozygotes within each population. In Switzerland, compared to Q7/Q7, two Q6/Q7 males departed earlier from the wintering grounds and arrived earlier to their colony in spring, while a single Q7/Q8 female was delayed for both phenophases. On the other hand, in the Po Plain, three Q6/Q7 individuals had a similar phenology compared to Q7/Q7. The Swiss data are suggestive for a role of genetic polymorphism at a candidate phenological gene in shaping migration traits, and support the idea that Clock polymorphism underlies phenological variation in birds. PMID:26197782

  13. Clock gene polymorphism and scheduling of migration: a geolocator study of the barn swallow Hirundo rustica.

    PubMed

    Bazzi, Gaia; Ambrosini, Roberto; Caprioli, Manuela; Costanzo, Alessandra; Liechti, Felix; Gatti, Emanuele; Gianfranceschi, Luca; Podofillini, Stefano; Romano, Andrea; Romano, Maria; Scandolara, Chiara; Saino, Nicola; Rubolini, Diego

    2015-01-01

    Circannual rhythms often rely on endogenous seasonal photoperiodic timers involving 'clock' genes, and Clock gene polymorphism has been associated to variation in phenology in some bird species. In the long-distance migratory barn swallow Hirundo rustica, individuals bearing the rare Clock allele with the largest number of C-terminal polyglutamine repeats found in this species (Q8) show a delayed reproduction and moult later. We explored the association between Clock polymorphism and migration scheduling, as gauged by light-level geolocators, in two barn swallow populations (Switzerland; Po Plain, Italy). Genetic polymorphism was low: 91% of the 64 individuals tracked year-round were Q7/Q7 homozygotes. We compared the phenology of the rare genotypes with the phenotypic distribution of Q7/Q7 homozygotes within each population. In Switzerland, compared to Q7/Q7, two Q6/Q7 males departed earlier from the wintering grounds and arrived earlier to their colony in spring, while a single Q7/Q8 female was delayed for both phenophases. On the other hand, in the Po Plain, three Q6/Q7 individuals had a similar phenology compared to Q7/Q7. The Swiss data are suggestive for a role of genetic polymorphism at a candidate phenological gene in shaping migration traits, and support the idea that Clock polymorphism underlies phenological variation in birds. PMID:26197782

  14. Polymorphisms in folate pathway genes are not associated with somatic nondisjunction in turner syndrome.

    PubMed

    Bispo, Adriana Valéria Sales; dos Santos, Luana Oliveira; de Barros, Juliana Vieira; Duarte, Andrea Rezende; Araújo, Jacqueline; Muniz, Maria Tereza Cartaxo; Santos, Neide

    2015-07-01

    Folate metabolism dysfunction can lead to DNA hypomethylation and abnormal chromosomal segregation. Previous investigations of this association have produced controversial results. Here we performed a case-control study in patients with Turner syndrome (TS) to determine the effects of genetic polymorphisms of folate pathway genes as potential risk factors for somatic chromosomal nondisjunction. TS is a useful model for this investigation because patients with TS show a high frequency of chromosome mosaicism. Here we investigated the possible association of polymorphisms of the MTHFR gene with TS risk, which has been previously investigated with controversial results. We also examined the effects of MTR, RFC1, and TYMS gene polymorphisms in TS for the first time. The risk was evaluated according to allelic and genotype (independent and combined) frequencies among 70 patients with TS and 144 age-matched healthy control subjects. Polymorphism genotyping was performed by PCR, PCR-RFLP, and PCR-ASA. The polymorphisms MTHFR 677C>T and 1298A>C, MTR 2756A>G, RFC1 80G>A, and TYMS 2R/3R-alone or in combinations-were not associated with the risk of chromosomal aneuploidy in TS. In conclusion, our present findings did not support a link between impaired folate metabolism and abnormal chromosome segregation leading to somatic nondisjunction in TS patients. PMID:25858821

  15. Impact of metallothionein gene polymorphisms on the risk of lung cancer in a Japanese population.

    PubMed

    Nakane, Hideo; Hirano, Minoru; Ito, Hidemi; Hosono, Satoyo; Oze, Isao; Matsuda, Fumihiko; Tanaka, Hideo; Matsuo, Keitaro

    2015-06-01

    Metallothioneins (MTs) are cysteine-rich proteins that act as antioxidants. A case-control study was conducted to assess the effects of gene polymorphisms in the MT region on the risk of lung cancer in Japanese subjects: 769 lung cancer cases and 939 non-cancer controls. Associations were evaluated using logistic regression models with adjustment for potential confounders (age, sex, and lifestyle factors including smoking, drinking, and green-yellow vegetable intake). We found five polymorphisms in the MT-1 gene region that showed statistically significant associations with lung cancer. Of these polymorphisms, rs7196890 showed the strongest association (odds ratio: 1.30, P = 0.004, 95% confidence interval: 1.09-1.55). The impact of the polymorphism decreased with the increase of smoking, and virtually no association with lung cancer was observed among heavy smokers whose pack-year values were 30 or more (odds ratio: 1.02, P = 0.93, 95% confidence interval: 0.67-1.55). These results suggest that polymorphisms in the MT gene are moderately associated with the risk of lung cancer and that the associations are modified by lifestyle factors. PMID:25174824

  16. The impact of detoxifying and repair gene polymorphisms on oxidative stress in ischemic stroke.

    PubMed

    Orhan, Gürdal; Elkama, Aylin; Mungan, Semra Öztürk; Eruyar, Esra; Karahalil, Bensu

    2016-06-01

    Stroke is a multifactorial disease caused by the combination of certain risk factors and genetic factors. There are possible risk factors having important role in the pathogenesis of stroke. The most important environmental factors are cigarette smoking and oxidative stress which have different sources. GST (M1, T1, P1) have major roles in detoxification of the products of oxidative stress and they are polymorphic. DNA damages can also be repaired by repair enzymes such as OGG1 and XRCC1 which are highly polymorphic and have pivotal roles in repair systems. In the present study, we investigated that polymorphisms in genes involved in detoxification and DNA-repair pathways might modify the individual's risk for ischemic stroke. Furthermore, the products of oxidative stress and antioxidant capacity were measured and the impact of gene polymorphism on them was evaluated. Our data showed that OGG1 Ser326Cys and XRCC1 Arg399Gln gene polymorphisms had impacts on the development of stroke. PMID:26936466

  17. Association of two Common Single Nucleotide Polymorphisms (+45T/G and +276G/T) of ADIPOQ Gene with Coronary Artery Disease in Type 2 Diabetic Patients

    PubMed Central

    Mohammadzadeh, Ghorban; Ghaffari, Mohammad-Ali; Heibar, Habib; Bazyar, Mohammad

    2016-01-01

    Background: Adiponectin, an adipocyte-secreted hormone, is known to have anti-atherogenic, anti-inflammatory, and anti-diabetic properties. In the present study, the association between two common single nucleotide polymorphisms (SNPs) (+45T/G and +276G/T) of ADIOPQ gene and coronary artery disease (CAD) was assessed in the subjects with type 2 diabetes (T2DM). Methods: Genotypes of two SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism in 200 subjects with T2DM (100 subjects with CAD and 100 without CAD). Results: The frequency of TT genotype of +276G/T was significantly elevated in CAD compared to controls (χ2=7.967, P=0.019). A similar difference was found in the allele frequency of +276G/T between two groups (χ2=3.895, P=0.048). The increased risk of CAD was associated with +276 TT genotype when compared to reference GG genotype (OR=5.158; 95% CI=1.016-26.182, P=0.048). However, no similar difference was found in genotype and allele frequencies of SNP +45T/G between two groups. There was a CAD protective haplotype combination of +276 wild-type and +45 mutant-type allele (276G-45G) (OR=0.37, 95% CI=0.16-0.86, P=0.022) in the subject population. Conclusion: Our findings indicated that T allele of SNP +276G/T is more associated with the increased risk of CAD in subjects with T2DM. Also, a haplotype combination of +45G/+276G of these two SNPs has a protective effect on the risk of CAD. PMID:26781170

  18. Association Study between Norepinephrine Transporter Gene Polymorphism and Schizophrenia in a Korean Population

    PubMed Central

    Choo, Mira; Hwang, Jung-A; Jeon, Sang Won; Oh, So-Young; Yoon, Ho-kyoung; Lee, Heon-Jeong

    2015-01-01

    Objective We aimed to investigate possible associations between three norepinephrine transporter gene (SLC6A2) single nucleotide polymorphisms (T182C, A3081T, and G1287A) and schizophrenia. Also, we investigated the relationships of those polymorphisms with clinical severity and characteristics of schizophrenia. Methods Participants were 220 schizophrenia patients in the acute phase and 167 healthy controls. The genotype, allele frequency, and haplotype of each group were analyzed for T182C, A3081T, and G1287A polymorphisms. Of the 220 schizophrenia patients, 163 patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) and the Korean version of the Calgary depression scale for schizophrenia (K-CDSS) at baseline. Results We found no significant differences between the schizophrenia patient group and the control group in genotype distribution or allele frequency of the three tested polymorphisms. Likewise, we could not find any significant differences in genotype or allele frequency by analyzing according to gender. In the haplotype study, no significant association emerged between specific haplotype combinations and schizophrenia. We also found no association between clinical scales (PANSS and K-CDSS) and the studied polymorphisms. Conclusion Our results suggest that the investigated polymorphisms of the NET gene are not associated with susceptibility to schizophrenia or its clinical features in a Korean population. However, this study remains significant because it is the first haplotype study to investigate associations between NET gene (SLC6A2) single nucleotide polymorphisms and schizophrenia in a Korean population. Future research with a larger sample size and more genetic markers is needed to replicate our results. PMID:26508968

  19. Heat shock protein 70-hom gene polymorphism and protein expression in multiple sclerosis.

    PubMed

    Boiocchi, C; Monti, M C; Osera, C; Mallucci, G; Pistono, C; Ferraro, O E; Nosari, G; Romani, A; Cuccia, M; Govoni, S; Pascale, A; Montomoli, C; Bergamaschi, R

    2016-09-15

    Immune-mediated and neurodegenerative mechanisms are involved in multiple sclerosis (MS). Growing evidences highlight the role of HSP70 genes in the susceptibility of some neurological diseases. In this explorative study we analyzed a polymorphism (i.e. HSP70-hom rs2227956) of the gene HSPA1L, which encodes for the protein hsp70-hom. We sequenced the polymorphism by polymerase chain reaction (PCR), in 191 MS patients and 365 healthy controls. The hsp70-hom protein expression was quantified by western blotting. We reported a strong association between rs2227956 polymorphism and MS risk, which is independent from the association with HSP70-2 rs1061581, and a significant link between hsp70-hom protein expression and MS severity. PMID:27609295

  20. Genetic dissection of psychopathological symptoms: insomnia in mood disorders and CLOCK gene polymorphism.

    PubMed

    Serretti, Alessandro; Benedetti, Francesco; Mandelli, Laura; Lorenzi, Cristina; Pirovano, Adele; Colombo, Cristina; Smeraldi, Enrico

    2003-08-15

    We investigated the possible effect of the 3111T/C CLOCK gene polymorphism on sleep disorders in a sample of 620 patients affected by major depressive disorder (MDD) and bipolar disorder (BP). We detected a significantly higher recurrence of initial (P = 0.0001), middle (P = 0.0009), and early (P = 0.0008) insomnia in homozygotes for the C variant and a similar trend concerning decreased need of sleep in BP (P = 0.0074). Other demographic and clinical features were found not related with CLOCK polymorphisms. This preliminary observation leads to hypothesize a possible involvement of the CLOCK gene polymorphism in the sleep disregulations in MDD and BP. PMID:12898572

  1. MHC class I BFIV gene polymorphisms in four Chinese native chicken breeds.

    PubMed

    Dai, Yin; Liu, Xue-Lan; Tang, Qing-Feng; Hu, Xiao-Miao; Shen, Xue-Huai; Zhang, Dan-Jun

    2016-09-01

    The major histocompatibility complex (MHC) includes the most polymorphic genes in vertebrates, and balancing selection has been proposed as a main evolutionary force. Here we present one of the first data sets examining the genetic characteristics of chicken MHC I BFIV molecules in four Chinese native breeds, sourced from different regions in China. In all, 89 BFIV alleles were isolated from 102 individuals sampled, and 13 repeated alleles were observed. No significant correlation was found between genetic differentiation and geographical distance in the phylogenetic tree. BFIV genes exhibited a high level of nucleotide polymorphisms, and most of the polymorphic sites were located in the peptide-binding region (PBR) encoded in exons 2 and 3. A comparison of the three-dimensional structures of PBRs in chicken BFIV and human HLA-A molecules revealed evident structural and functional similarities. The results suggested that MHC I molecules had similar structural features in different species. PMID:27168230

  2. Dopamine D{sub 3} receptor gene: Organization transcript variants, and polymorphism associated with schizophrenia

    SciTech Connect

    Griffon, N.; Pilon, C.; Martres, M.P.

    1996-02-16

    DNA fragments from a genomic library were used to establish the partial structure of the human dopamine D{sub 3} receptor gene (DRD3). Its coding sequence contains 6 exons and stretches over 40,000 base pairs. The complete DRD3 transcript and three shorter variants, in which the second and/or third exon are deleted, were detected in similar proportions in brains from four controls and three psychiatric patients. The Msp I polymorphism was localized in the fifth intron of the gene, 40,000 base pairs downstream the Bal I polymorphism and a PCR-based method was developed for genotyping this polymorphism. The distributions of the Msp I and Bal I genotypes were not independent in 297 individuals ({chi}{sup 2} = 10.5, df = 4, P = 0.03), but only a weak association was found between allele 1 of the Bal I polymorphism and allele 2 of the Msp I polymorphism ({chi}{sup 2} = 3.99, df = 1, P = 0.04). The previously reported association between homozygosity at both alleles of the Bal I polymorphism and schizophrenia was presently maintained in an extended sample, comprising 119 DSM-III-R chronic schizophrenics and 85 controls ({chi}{sup 2}= 5.3, df = 1, P = 0.02) and found more important in males than in females. The presence of the Bal I allele 2 is associated with an early age at onset, particularly in males (df = 35, t value = 2.6, P = 0.014). In the same sample, allelic frequencies, genotype counts, and proportion of homozygotes for the Msp I polymorphism did not differ between schizophrenics and controls ({chi}{sup 2}= 0.06, df = 1, P = 0.80, {chi}{sup 2} = 0.22, df = 1, P = 0.90 and {chi}{sup 2} = 0.16, df = 1, P = 0.69, respectively). The large distance of the Msp I polymorphism from the Bal I polymorphism and its localization in the 3{prime} part of the gene may explain the discrepant results obtained with the two polymorphisms. 36 refs., 2 figs., 4 tabs.

  3. Estrogen Receptor Alpha (ESR1) Gene Polymorphisms in Pre-eclamptic Saudi Patients

    PubMed Central

    El-Beshbishy, Hesham A.; Tawfeek, Manal A.; Al-Azhary, Nevin M.; Mariah, Reham A.; Habib, Fawzia A.; Aljayar, Lamya; Alahmadi, Abrar F.

    2015-01-01

    Objectives: Pre-eclampsia causes maternal mortality worldwide. Estrogen receptor alpha (ESR1) gene polymorphisms were responsible for cardiovascular diseases. This case control study was conducted to investigate whether 2 polymorphic genes of ESR1 are associated with pre-eclampsia among Saudi women in Madina city, Saudi Arabia. Methods: Blood samples from 97 pre-eclamptic and 94 healthy pregnant women were analyzed using restriction fragment length polymorphism-polymerase chain reaction method. All the subjects were recruited randomly from outpatient clinics of Madina Maternity Children Hospital (MMCH), Madina, Saudi Arabia, between Dec. 2012 and Jan. 2014. Results: There was no association between pre-eclampsia and PvuII and XbaI ESR1 gene polymorphisms individually. TT/AA and TT/AG genotype combination existed significantly in pre-eclamptic patients compared to control. The frequency of PvuII and XbaI combined TT/AA genotypes between pre-eclamptic women was 36.1% vs 9.6%, however, frequency of PvuII and XbaI combined TT/AG genotypes between pre-eclamptic women was 3.1% vs 17%, compared to control. The homozygous T-A haplotype carriers showed high pre-eclampsia risk, independent of pregnancy, BMI and smoking status (adjusted odds ratio (OR): 3.26, 95% confidence interval (CI):1.71-9.21). The heterozygous T-A haplotype carriers did not differ from that of non-carriers (adjusted OR: 1.12, 95% CI: 0.47-2.75). No association was observed between pre-eclampsia and T-G, C-G and C-A haplotype of PvuII and XbaIESR1 gene polymorphisms. Conclusions: T-A haplotype of homozygous associated with pre eclampsia not heterozygous carriers of ESR 1 PvuII and XbaI gene polymorphisms elicited high risk of pre-eclampsia. GG genotype of XbaI polymorphism decreased pre-eclampsia risk. Further studies using larger sample size are recommended to investigate the ESR 1 gene polymorphisms associated with pre-eclampsia. PMID:26430422

  4. Cytosolic phospholipase A{sub 2} gene in human and rat: Chromosomal localization and polymorphic markers

    SciTech Connect

    Tay, A.; Simon, J.S.; Jacob, H.J.

    1995-03-01

    The authors report the chromosomal localization and a simple sequence repeat (SSR) in the cytosolic phospholipase A{sub 2} (cPLA{sub 2}) gene in both human and rat. A (CA){sub 18} repeat in the promoter of the rat gene was determined to exhibit length polymorphism when analyzed using the polymerase chain reaction (PCR) in 19 different inbred rat strains. Genotyping for this marker in 234 F{sub 2} progeny of a SHRXBN intercross mapped the gene to rat chromosome 13. Using a PCR strategy, a fragment of the promoter for the human gene was isolated, and a (CA){sub 18} repeat was identified. Since this marker displayed a low heterozygosity index, they also identified a mononucleotide repeat in the promoter for cPLA{sub 2} that displayed a polymorphism information content value of 0.76. The human gene was mapped using fluorescence in situ hybridization (FISH) to chromosome 1q25. Of interest, the gene encoding the enzyme prostaglandin-endoperoxide synthase 2 (cyclooxygenase-2), which acts on the arachidonic acid product of cPLA{sub 2}, was previously localized to this same chromosomal region, raising the possibility of coordinate regulation. Identification of intragenic markers may facilitate studies of polymorphic variants of these genes as candidates for disorders in which perturbations of the eicosanoid cascade may play a role. 20 refs., 3 figs., 2 tabs.

  5. Association between polymorphisms of the CRH and POMC genes with economic traits in Korean cattle (Hanwoo).

    PubMed

    Seong, J; Kong, H S

    2015-01-01

    The corticotrophin-releasing hormone (CRH) and proo-piomelanocortin (POMC) genes are considered to play an important role in the growth and development of mammals. In this study, the bovine CRH and POMC genes were characterized to detect genetic variation at these loci in relation to economic traits in Korean cattle (Hanwoo). Nine single nucleotide polymorphisms (SNPs; C148T, A186G, A234C, G269A, G1030A, G1084A, A1136C, G1179C, and A1439G) were detected in the CRH gene, and six SNPs (C7017T, A7027T, C7050T, G7063T, C7160T, and C7221T) were detected in the POMC gene. Three SNPs in the CRH gene (G1030A, G1084A, and G1179C) were missense mutations, and three SNPs in the POMC gene (C7017T, A7027T, and C7160T) were missense mutations. Statistical analysis indicated that one CRH polymorphism (G1084A) was signifi-cantly (P = 0.05) associated with the longissimus dorsi muscle area (LMA), and a POMC polymorphism (C7221T) significantly influenced LMA and marbling scores. A significant interaction was detected be-tween CRH and POMC in relation to carcass weight and LMA. These results indicate that CRH and POMC may be candidate genes for car-cass traits, and suggest that the interaction between CRH and POMC strongly affects carcass traits in cattle. PMID:26400272

  6. TLR2, TLR3, TLR4 and CD14 gene polymorphisms associated with oral lichen planus risk.

    PubMed

    Stanimirovic, Dragan; Zeljic, Katarina; Jankovic, Ljiljana; Magic, Marko; Hadzi-Mihajlovic, Milos; Magic, Zvonko

    2013-10-01

    The aim of this study was to assess whether polymorphisms in toll-like receptor (TLR) and cluster of differentiation 14 (CD14) genes are associated with oral lichen planus (OLP) risk and clinical course of the disease. The study group consisted of 101 patients with confirmed OLP and 104 healthy blood donors without systemic or oral mucosal diseases. Single nucleotide polymorphisms of TLR2 (rs3804099), TLR3 (rs3775291 and rs5743312), TLR4 (rs4986790 and rs4986791), and CD14 (rs2569190) genes were genotyped using real-time PCR or PCR-restriction fragment length polymorphism (PCR-RFLP). The rs5743312 TLR3 gene polymorphism was associated with increased OLP risk in comparison with the wild type genotype (OR = 15.984, P = 0.011). No association with OLP risk was observed for the polymorphisms studied in TLR2, TLR4 and CD14 genes or for the rs3775291 polymorphism of the TLR3 gene. The polymorphisms of the TLR3 gene were in linkage disequilibrium (D' = 1, r(2) = 0.1). Identified haplotypes were not associated with the risk of OLP. The findings of the current study suggest that the TT genotype of the rs5743312 TLR3 gene polymorphism may play a significant role in the aetiology of OLP. PMID:24028589

  7. Contribution of protein Z gene single-nucleotide polymorphism to systemic lupus erythematosus in Egyptian patients.

    PubMed

    Yousry, Sherif M; Shahin, Rasha M H; El Refai, Rasha M

    2016-09-01

    Protein Z has been reported to exert an important role in inhibiting coagulation. Polymorphisms in the protein Z gene (PROZ) may affect protein Z levels and thus play a role in thrombosis. This study aimed to investigate the prevalence and clinical significance of protein Z gene G79A polymorphism in Egyptian patients with systemic lupus erythematosus (SLE). We studied the distribution of the protein Z gene (rs17882561) (G79A) single-nucleotide polymorphism by PCR-restriction fragment length polymorphism in 100 Egyptian patients with SLE and 100 age, sex, and ethnically matched controls. There was no statistically significant difference in the distribution of the genotypes between SLE patients and the control group in our study (P = 0.103). But a statistically significant difference in the frequency of the alleles between SLE patients and controls was observed (P = 0.024). Also a significant association was detected between protein Z genotypes (and also A allele) and thrombosis, which is one of the manifestations of SLE (P = 0.004 and P = 0.001, respectively). Moreover, we observed a significant association between the protein Z AA and GA genotypes (and also A allele) and the presence of anticardiolipin antibodies (P = 0.016 and P = 0.004, respectively). The minor A allele of the G79A polymorphism in the protein Z gene might contribute to the genetic susceptibility of SLE in Egyptian patients. Also, an influence for this polymorphism on some of the disease manifestations has been elucidated, so protein Z G79A AG/AA may be a risk factor for thrombosis. PMID:26761586

  8. Polymorphisms in cell cycle regulatory genes, urinary arsenic profile and urothelial carcinoma

    SciTech Connect

    Chung, C.-J.; Huang, C.-J.; Pu, Y.-S.; Su, C.-T.; Huang, Y.-K.; Chen, Y.-T.; Hsueh, Y.-M.

    2008-10-15

    Introduction: Polymorphisms in p53, p21 and CCND1 could regulate the progression of the cell cycle and might increase the susceptibility to inorganic arsenic-related cancer risk. The goal of our study was to evaluate the roles of cell cycle regulatory gene polymorphisms in the carcinogenesis of arsenic-related urothelial carcinoma (UC). Methods: A hospital-based case-controlled study was conducted to explore the relationships among the urinary arsenic profile, 8-hydroxydeoxyguanosine (8-OHdG) levels, p53 codon 72, p21 codon 31 and CCND1 G870A polymorphisms and UC risk. The urinary arsenic profile was determined using high-performance liquid chromatography (HPLC) and hydride generator-atomic absorption spectrometry (HG-AAS). 8-OHdG levels were measured by high-sensitivity enzyme-linked immunosorbent assay (ELISA) kits. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymerase (PCR-RFLP). Results: Subjects carrying the p21 Arg/Arg genotype had an increased UC risk (age and gender adjusted OR = 1.53; 95% CI, 1.02-2.29). However, there was no association of p53 or CCND1 polymorphisms with UC risk. Significant effects were observed in terms of a combination of the three gene polymorphisms and a cumulative exposure of cigarette smoking, along with the urinary arsenic profile on the UC risk. The higher total arsenic concentration, monomethylarsonic acid percentage (MMA%) and lower dimethylarsinic acid percentage (DMA%), possessed greater gene variant numbers, had a higher UC risk and revealed significant dose-response relationships. However, effects of urinary 8-OHdG levels combined with three gene polymorphisms did not seem to be important for UC risk. Conclusions: The results showed that the variant genotype of p21 might be a predictor of inorganic arsenic-related UC risk.

  9. Cancer Familial Aggregation (CFA) and G446A polymorphism in ARLTS1 gene.

    PubMed

    Masojć, Bartłomiej; Mierzejewski, Marek; Cybulski, Cezary; van de Wetering, Thierry; Debniak, Tadeusz; Górski, Bohdan; Jaworowska, Ewa; Tarnowska, Czesława; Lenner, Marcin; Scott, Rodney J; Lubiński, Jan

    2006-09-01

    ARLTS1--a member of ADP-ribosylation factor family, is a newly described candidate tumour suppressor gene. Recent studies show that a nonsense polymorphism, G446A (Trp149Stop), in ARLTS1 gene is significantly more frequent in familial cancer cases than in sporadic cancer cases. This study presents analysis of the germ-line G446A polymorphism in the ARLTS1 gene among 1686 consecutively collected patients with breast cancer, prostate cancer, malignant melanoma, thyroid papillary cancer or laryngeal cancer in Poland. The G446A allele was present in 1.81% (9/497) breast cancer patients, 1.46% (5/343) prostate cancer patients, 1.76% (7/397) melanoma patients, 1.65% (3/182) thyroid papillary carcinoma patients and 2.68% (8/299) of laryngeal cancer patients. The frequency of this polymorphism in the control group was 1.45% (8/552). Differences in the frequency of the G446A polymorphism between case and control groups were not statistically significant. In addition, there was no significant difference in the number of Cancer Familial Aggregations (CFA) among breast, prostate, thyroid or laryngeal cancer cases harbouring the G446A polymorphism, when compared to the G446A negative cases. Interestingly out of the CFA melanoma cases, 4/6 (66.6%) were found to harbour the change compared to only 20.2% (69/341) sporadic melanoma cases. This difference was statistically significant (p = 0.02, OR = 7.8). The results of this study suggest that the G446A in ARLTS1 gene is probably not associated with an increased risk of sporadic breast cancer, prostate cancer, melanoma, thyroid papillary cancer or laryngeal cancer. Moreover, the G446A polymorphism is not significantly more frequent in CFA cases except for families in which the proband had melanoma. To confirm this result more cases of melanoma should be analysed. PMID:16570116

  10. Renalase Gene rs2576178 Polymorphism in Hemodialysis Patients: Study in Bosnia and Herzegovina

    PubMed Central

    Kiseljakovic, Emina; Mackic-Djurovic, Mirela; Hasic, Sabaheta; Beciragic, Amela; Valjevac, Amina; Alic, Lejla; Resic, Halima

    2016-01-01

    Introduction: Renalase is a protein secreted in kidneys and considered as a blood pressure modulator. High rates of hypertension and its regulation in patients on hemodialysis demands search for potential cause and treatment. The aim of this study was to determine the genotype and allele frequencies of renalase gene rs2576178 polymorphism in population from Bosnia and Herzegovina. Also, the objective of present study was to find the possible association between renalase gene rs2576178 polymorphism and hypertension in patients on hemodialysis. Material and Methods: The genotype of renalase gene rs2576178 polymorphism was determined in 137 participants (100 patients on hemodialysis and 37 controls), using polymerase chain reaction (PCR) and subsequent cleavage with MspI restriction endonuclease. Genotype and allele frequencies were assessed for Hardy-Weinberg equilibrium using a Chi-squared test. The value of P<0.05 was considered as statistically significant. Results: Comparison of genotype distribution and allele frequency in participants on hemodialysis with and without hypertension, and healthy control showed no statistical difference. Conclusion: The results of the study suggest that renalase gene rs2576178 polymorphism is not a factor that influences blood pressure in patients on hemodialysis. PMID:26980928

  11. Association of a single nucleotide polymorphism of calpain 1 gene with meat tenderness of the yak

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The association of a single nucleotide polymorphism (SNP) of calpain 1 (CAPN1) gene with shear force of 2.54 cm steaks from M. longissimus dorsi from Gannan yaks (Bos grunniens, n = 181) was studied. The experimental design was a repeated measures with the main unit in a completely randomized design...

  12. BIALLELIC POLYMORPHISM IN THE INTRON REGION OF B-TUBULIN GENE OF CRYPTOSPORIDIUM PARASITES

    EPA Science Inventory

    Nucleotide sequencing of polymerase chain reaction-amplified intron region of the Cryptosporidium parvum B-tubulin gene in 26 human and 15 animal isolates revealed distinct genetic polymorphism between the human and bovine genotypes. The separation of 2 genotypes of C. parvum is...

  13. Polymorphisms in the hemagglutinin gene influenced the viral shedding of pandemic 2009 influenza virus in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The contribution of influenza virus quasi-species for transmission efficiency and replication is poorly understood. In the present study we show that naturally occurring polymorphisms present in the hemagglutinin (HA) gene of two 2009 pandemic H1N1 isolates, A/California/04/2009 (Ca/09) and A/Mexico...

  14. Copy number polymorphism in the α-globin gene cluster of European rabbit (Oryctolagus cuniculus)

    PubMed Central

    Campos, R; Storz, J F; Ferrand, N

    2012-01-01

    Comparative genomic studies have revealed that mammals typically possess two or more tandemly duplicated copies of the α-globin (HBA) gene. The domestic rabbit represents an exception to this general rule, as this species was found to possess a single HBA gene. Previous electrophoretic surveys of HBA polymorphism in natural populations of the European rabbit (Oryctolagus cuniculus) revealed extensive geographic variation in the frequencies of three main electromorphs. The variation in frequency of two electromorphs is mainly partitioned between two distinct subspecies of European rabbit, and a third is restricted to the hybrid zone between the two rabbit subspecies in Iberia. Here we report the results of a survey of nucleotide polymorphism, which revealed HBA copy number polymorphism in Iberian populations of the European rabbit. By characterizing patterns of HBA polymorphism in populations from the native range of the European rabbit, we were able to identify the specific amino-acid substitutions that distinguish the previously characterized electromorphs. Within the hybrid zone, we observed the existence of a second HBA gene duplicate, named HBA2, that mostly represents a novel sequence haplotype, which occurs in higher frequency within the hybrid zone, and thus appears to have arisen in hybrids of the two distinct subspecies. Although this novel gene is also present in other wild Iberian populations, it is almost absent from French populations, which suggest a recent ancestry, associated with the establishment of the post-Pleistocene contact zone between the two European rabbit subspecies. PMID:22146981

  15. Identification of genomic polymorphisms in upstream elements of the bovine CYP3A28 gene

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The cytochrome P450 (CYP) enzyme family consists of a group of heme-containing monooxygenases that participate in metabolism and phase I detoxification. Previously, our group reported that the coding sequence for the CYP3A28 gene in cattle was polymorphic and related to cattle performance on toxic t...

  16. Clinical Efficacy of Fluvoxamine and Functional Polymorphism in a Serotonin Transporter Gene on Childhood Autism

    ERIC Educational Resources Information Center

    Sugie, Yoko; Sugie, Hideo; Fukuda,Tokiko; Ito, Masataka; Sasada, Yumiko; Nakabayashi, Mutsumi; Fukashiro, Kazunobu; Ohzeki, Takehiko

    2005-01-01

    We studied the correlation between response to fluvoxamine and serotonin transporter gene promoter region polymorphism (5-HTTLPR). Eighteen children with autistic disorder completed a 12-week double-blind, placebo-controlled, randomized crossover study of fluvoxamine. Behavioral assessments were obtained before and at 12 weeks of treatment.…

  17. ASSOCIATION OF RESISTANCE TO AVIAN COCCIDIOSIS WITH SINGLE NUCLEOTIDE POLYMORPHISMS IN THE ZYXIN GENE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our previous genetic studies demonstrated that resistance to avian coccidiosis was linked with microsatellite markers LEI0071 and LEI0101 on chromosome 1. In this study, the associations between parameters of resistance to coccidiosis and single nucleotide polymorphisms (SNPs) in 3 candidate genes ...

  18. The effects of single nucleotide polymorphisms (SNPs) of calpastatin (CAST) gene on meat tenderness of yak.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The association of single nucleotide polymorphisms (SNPs) of calpastatin (CAST) gene with shear force of 2.54 cm steaks from M. longissimus dorsi from Gannan yaks (Bos grunniens, n=181) was studied. Yaks were harvested at 2, 3, and 4 yr of age (n=51, 59, and 71, respectively), and samples of each ya...

  19. Mutations and a polymorphism in the factor VIII gene discovered by denaturing gradient gel electrophoresis

    SciTech Connect

    Kogan, S.; Gitschier, J. )

    1990-03-01

    Hemophilia A results from mutations in the gene coding for coagulation factor VIII. The authors gradient gel electrophoresis to screen for mutations in the region of the factor VIII gene coding for the first acidic domain. Amplification primers were designed employing the MELTMAP computer program to optimize the ability to detect mutations. Screening of amplified DNA from 228 unselected hemophilia A patients revealed two mutations and one polymorphism. Rescreening the same population by making heteroduplexes between amplified patient and control samples prior to electrophoresis revealed one additional mutation. The mutations include two missense and one 4-base-pair deletion, and each mutation was found in patients with severe hemophilia. The polymorphism, located adjacent to the adenine branch site in intron 7, is useful for genetic prediction in some cases where the Bcl I and Xba I polymorphisms are uninformative. These results suggest that DNA amplification and denaturing gradient gel electrophoresis should be an excellent strategy for identifying mutations and polymorphisms in defined regions of the factor VIII gene and other large genes.

  20. Landscape heterogeneity predicts gene flow in a widespread polymorphic bumble bee, Bombus bifarius (Hymentoptera: Apidae).

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bombus bifarius is a widespread bumble bee that occurs in montane regions of western North America. This species has several major color polymorphisms, and shows evidence of genetic structuring among regional populations. We test whether this structure is evidence for discrete gene flow barriers tha...

  1. Identification of Staphylococcus spp. by PCR-Restriction Fragment Length Polymorphism of gap Gene

    PubMed Central

    Yugueros, Javier; Temprano, Alejandro; Sánchez, María; Luengo, José María; Naharro, Germán

    2001-01-01

    Oligonucleotide primers specific for the Staphylococcus aureus gap gene were previously designed to identify 12 Staphylococcus spp. by PCR. In the present study, AluI digestion of PCR-generated products rendered distinctive restriction fragment length polymorphism patterns that allowed 24 Staphylococcus spp. to be identified with high specificity. PMID:11574593

  2. The CXCR2 Gene Polymorphism Is Associated with Stroke in Patients with Essential Hypertension

    PubMed Central

    Timasheva, Yanina R.; Nasibullin, Timur R.; Mustafina, Olga E.

    2015-01-01

    Hypertension is the major risk factor for stroke, and genetic factors contribute to its development. Inflammation has been hypothesized to be the key link between blood pressure elevation and stroke. We performed an analysis of the association between inflammatory mediator gene polymorphisms and the incidence of stroke in patients with essential hypertension (EH). The study group consisted of 625 individuals (296 patients with noncomplicated EH, 71 hypertensive patients with ischemic stroke, and 258 control subjects). Both patients and controls were ethnic Tatars originating from the Republic of Bashkortostan (Russian Federation). The analysis has shown that the risk of ischemic stroke was associated with the CXCR2 rs1126579 polymorphism. Our results indicate that among patients with EH, the heterozygous genotype carriers had a higher risk of stroke (OR = 1.72, 95% CI 1.01-2.92), whereas the CXCR2*C/C genotype was protective against stroke (OR = 0.32, 95% CI 0.12-0.83). As shown by the gene-gene interaction analysis, the CXCR2 rs1126579 polymorphism was also present in all genotype/allele combinations associated with the risk of stroke. Genetic patterns associated with stroke also included polymorphisms in the CCL2, CCL18, CX3CR1, CCR5, and CXCL8 (IL8) genes, although no association between these loci and stroke was detected by individual analysis. PMID:26648969

  3. Apolipoprotein E gene polymorphisms and retinal vascular signs: The Atherosclerosis Risk in Communities (ARIC) Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our objective was to examine the association between apolipoprotein E (APOE) gene polymorphisms and retinal microvascular signs. We used a population-based, cross-sectional study. Participants from the Atherosclerosis Risk in Communities Study (n=10,036; aged 49-73 years) had retinal photographs tak...

  4. Relation between functional polymorphism of catalase gene (-262C>T) and recurrent depressive disorder.

    PubMed

    Galecki, Piotr; Szemraj, Janusz; Zboralski, Krzysztof; Florkowski, Antoni; Lewinski, Andrzej

    2009-01-01

    Numerous studies have provided information indicating the involvement of oxidative stress in the pathophysiology of depressive disorder (DD). The antioxidative system protects against the effects caused by reactive oxygen species (ROS). Catalase (CAT) is one of antioxidative enzymes observed to change their levels in the course of depression. The enzyme decomposes hydrogen peroxide (H(2)O(2)), whose overproduction is a result of many processes taking place in depression. Therefore, functional polymorphism of the CAT gene can be a candidate marker of the risk of depression. The presented study assessed the correlation between -262C>T polymorphism of the CAT gene, which influences the increase of CAT expression and activity, and the risk of depression development. The study, carried out on a homogeneous group recruited from the Polish population, enrolled 149 healthy subjects and 149 depressive patients. The groups were age-matched. The obtained results indicate no correlation between -262C>T polymorphism of the CAT gene (both with respect to genotype distribution and allele frequency) and the risk of depression. Nevertheless, further studies assessing the correlations between depression and polymorphism of the genes encoding antioxidative enzymes on larger groups of subjects should be undertaken. PMID:19855359

  5. The Association between Infants' Self-Regulatory Behavior and MAOA Gene Polymorphism

    ERIC Educational Resources Information Center

    Zhang, Minghao; Chen, Xinyin; Way, Niobe; Yoshikawa, Hirokazu; Deng, Huihua; Ke, Xiaoyan; Yu, Weiwei; Chen, Ping; He, Chuan; Chi, Xia; Lu, Zuhong

    2011-01-01

    Self-regulatory behavior in early childhood is an important characteristic that has considerable implications for the development of adaptive and maladaptive functioning. The present study investigated the relations between a functional polymorphism in the upstream region of monoamine oxidase A gene (MAOA) and self-regulatory behavior in a sample…

  6. Association of AGT M235T gene polymorphism with HSP/HSPN risk.

    PubMed

    Mao, Song; Huang, Songming

    2015-02-01

    To evaluate the association between angiotensinogen (AGT) gene polymorphism and the risk of Henoch-Schönlein purpura (HSP)/Henoch-Schönlein purpura nephritis (HSPN) we searched the eligible studies through Pub Med, Embase, Cochrane, and China National Knowledge Infrastructure (CNKI) databases according to predefined criteria. A random-effects model was used to calculate the combined odds ratios (ORs) and its corresponding 95% confidence interval (CI). Five studies were recruited for the analysis of the association between AGT M235T gene polymorphism and HSP/HSPN risk. M allele was associated with lower risk of HSP in adult (p = 0.050), TT genotype was associated with the susceptibility to HSP in adult (p = 0.039). AGT M235T gene polymorphism was not associated with HSP risk in children. No marked association was observed between AGT M235T gene polymorphism and HSPN risk. No evidence of publication bias was observed. In conclusion, M allele might be a protective factor against the HSP risk in adult, TT genotype might be a risk factor for the susceptibility to HSP in adult. However, further larger studies should be performed in the future. PMID:25350836

  7. No Polymorphism in Plasmodium falciparum K13 Propeller Gene in Clinical Isolates from Kolkata, India

    PubMed Central

    Chatterjee, Moytrey; Ganguly, Swagata; Saha, Pabitra; Bankura, Biswabandhu; Basu, Nandita; Das, Madhusudan; Guha, Subhasish K.; Maji, Ardhendu K.

    2015-01-01

    Molecular markers associated with artemisinin resistance in Plasmodium falciparum are yet to be well defined. Recent studies showed that polymorphisms in K13 gene are associated with artemisinin resistance. The present study was designed to know the pattern of polymorphisms in propeller region of K13 gene among the clinical isolates collected from urban Kolkata after five years of ACT implementation. We collected 59 clinical isolates from urban Kolkata and sequenced propeller region of K13 gene in 51 isolates successfully. We did not find any mutation in any isolate. All patients responded to the ACT, a combination of artesunate + sulphadoxine-pyrimethamine. The drug regimen is still effective in the study area and there is no sign of emergence of resistance against artemisinin as evidenced by wild genotype of K13 gene in all isolates studied. PMID:26688755

  8. Frequency of mutations and polymorphisms in borderline ovarian tumors of known cancer genes

    PubMed Central

    Stemke-Hale, Katherine; Shipman, Kristy; Kitsou-Mylona, Isidora; de Castro, David Gonzalez; Hird, Vicky; Brown, Robert; Flanagan, James; Hani Gabra, H; Mills, Gordon B.; Agarwal, R; El-Bahrawy, Mona

    2013-01-01

    Borderline ovarian tumors represent an understudied subset of ovarian tumors. Most studies investigating aberrations in borderline tumors have focused on KRAS/BRAF mutations. In this study we conducted an extensive analysis of mutations and single nucleotide polymorphisms in borderline ovarian tumors. Using the Sequenom MassARRAY platform we investigated 160 mutations/polymorphisms in 33 genes involved in cell signalling, apoptosis, angiogenesis, cell cycle regulation, and cellular senescence. Of 52 tumors analysed, 33 were serous, 18 mucinous and 1 endometrioid. KRAS c.35G>A p.Gly12Asp mutations were detected in 8 tumors (6 serous and 2 mucinous), BRAF V600E mutations in 2 serous tumors, and PIK3CA H1047Y and PIK3CA E542K mutations in a serous and an endometrioid BOT respectively. CTNNB1 mutation was detected in a serous tumor. Potentially functional polymorphisms were found in VEGF, ABCB1, FGFR2 and PHLPP2. VEGF polymorphisms were the most common and detected at 4 loci. PHLPP2 polymorphisms were more frequent in mucinous as compared to serous tumors (p=0.04), with allelic imbalance in one case. This study represents the largest and most comprehensive analysis of mutations and functional single nucleotide polymorphisms in borderline ovarian tumors to date. At least 25% of borderline ovarian tumors harbour somatic mutations associated with potential response to targeted therapeutics. PMID:23174937

  9. Adiponectin Regulates Vascular Endothelial Growth Factor-C Expression in Macrophages via Syk-ERK Pathway

    PubMed Central

    Hu, Di; Fukuhara, Atsunori; Miyata, Yugo; Yokoyama, Chieko; Otsuki, Michio; Kihara, Shinji; Shimomura, Iichiro

    2013-01-01

    Adiponectin is exclusively expressed in adipose tissues and exhibits protective effects against cardiovascular and metabolic diseases. It enhances AMP-activated kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα) signaling in the liver and skeletal muscles, however, its signaling pathways in macrophages remain to be elucidated. Here, we show that adiponectin upregulated the expression of vascular endothelial growth factor (VEGF)-C, and induced phosphorylation of extracellular signal-regulated kinase (ERK) in macrophages. Inhibition of Syk abrogated adiponectin-induced VEGF-C expression and ERK phosphorylation. Furthermore, inhibition of ERK blocked the induction of VEGF-C gene. Inhibition of Syk, but not that of ERK, abrogated adiponectin-induced expression of cyclooxygenase (COX)-2, tissue inhibitor of metalloproteinase (TIMP)-1, and interleukin (IL)-6. These results indicate that adiponectin regulates VEGF-C expression via Syk-ERK pathway in macrophages. PMID:23424645

  10. Pesticide, Gene Polymorphisms and Bladder Cancer among Egyptian Agricultural Workers

    PubMed Central

    Amr, Sania; Dawson, Rebecca; Saleh, Doa’a A.; Magder, Laurence S.; St. George, Diane Marie; El-Daly, Mai; Squibb, Katherine; Mikhail, Nabiel N.; Abdel-Hamid, Mohamed; Khaled, Hussein; Loffredo, Christopher A.

    2013-01-01

    We examined the associations between pesticide exposure, genetic polymorphisms for NAD(P)H:quinone oxidoreductase I (NQO1) and superoxide dismutase 2 (SOD2), and urinary bladder cancer risk among male agricultural workers in Egypt. We used logistic regression to analyze data from a multi-center case-control study and estimate adjusted odds ratio (OR) and 95% CI (confidence interval) Exposure to pesticides was associated with increased bladder cancer risk (1.68 (1.23–2.29)) in a dose-dependent manner. The association was slightly stronger for urothelial (1.79 (1.25–2.56) than for squamous cell carcinoma (1.55 (1.03–2.31)), and among participants with combined genotypes for low NQO1 and high SOD2 (2.14 (1.19–3.85) activities as compared to those with high NQO1 and low SOD2 genotypes (1.53 (0.73–3.25)). In conclusion, among male agricultural workers in Egypt, pesticide exposure is associated with bladder cancer risk and possibly modulated by genetic polymorphism. PMID:24219772

  11. Polymorphism of the Transferrin Gene in Eye Diseases: Keratoconus and Fuchs Endothelial Corneal Dystrophy

    PubMed Central

    Wójcik, Katarzyna A.; Jiménez-García, Manuel P.; Kaminska, Anna; Polakowski, Piotr; Szaflik, Jerzy; Szaflik, Jacek P.

    2013-01-01

    Oxidative stress may play a role in the pathogenesis of keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD). Iron may promote the stress by the Fenton reaction, so its homeostasis should be strictly controlled. Transferrin is essential for iron homeostasis because it transports iron from plasma into cells. The malfunction of transferrin, which may be caused by variation in its gene (TF) variation, may contribute to oxidative stress and change KC and FECD risk. To verify this hypothesis we investigated the association between three polymorphisms of the TF gene, g.3296G>A (rs8177178), g.3481A>G (rs8177179), and c.–2G>A (rs1130459), and KC and FECD occurrence. Genotyping was performed in blood lymphocytes in 216 patients with KC, 130 patients with FECD and 228 controls by PCR-RFLP. We studied also the influence of other risk factors. The A/A genotype and the A allele of the g.3296G>A polymorphism were associated with KC occurrence, while the G allele was negatively correlated with it. We observed a decrease in KC occurrence associated with the A/G genotype of the g.3481A>G polymorphism. We did not find any association between the c.–2G>A polymorphism and KC. No association was found between all three polymorphisms and FECD occurrence. PMID:24350254

  12. Association study of ankylosing spondylitis and polymorphisms in ERAP1 gene in Zhejiang Han Chinese population.

    PubMed

    Liu, Yangbo; Li, Liangda; Shi, Shanfen; Chen, Xin; Gao, Jianqing; Zhu, Minyu; Yuan, Jiandong

    2016-02-01

    The susceptibility loci of ERAP1 polymorphisms have been found to be strongly associated with ankylosing spondylitis (AS). The researches in multiple ethnic cohorts suggested that the population attributable risk in ERAP1 polymorphisms is at a high significance level. This study was undertaken to estimate the prevalence and incidence of subsets of AS and investigate the specific variants of ERAP1 polymorphisms in AS susceptibility, in the Han ethnic Chinese population in Zhejiang Province. AS patients were selected, diagnosed, and confirmed by a qualified rheumatologist. The basal clinical and demographic characteristics were compared with all subjects. Genotypes for eight selected single nucleotide polymorphisms (SNPs) in ERAP1 gene (rs27038, rs27037, rs27434, rs27980, rs7711564, rs30187, rs10050860, and rs17482078) were determined by using the Sequenom MassARRAY iPLEX platform in Zhejiang Han Chinese population. Association analyses were performed on the whole genotyped data set in 707 unrelated ankylosing spondylitis cases and 837 ethnically matched controls. We observed the strongest association between AS and HLA-B27, which confers over 90 % of ankylosing spondylitis cases. Moreover, we found three loci of ERAP1 polymorphisms were at a high significance level (rs27037 P = 0.00451; rs27434 P = 0.00012; rs27980 P = 0.00682) with AS in Zhejiang population. We also confirmed polymorphism locus of ERAP1 previously reported association with AS (rs27434; P = 5.3 × 10(-12)). Our results indicated a difference in the mechanism of susceptibility loci in subsets of Zhejiang Han Chinese population and provided further evidence that rs27434 is the key polymorphism associated with AS in ERAP1 gene. PMID:26350268

  13. Risk Factors in Normal-Tension Glaucoma and High-Tension Glaucoma in relation to Polymorphisms of Endothelin-1 Gene and Endothelin-1 Receptor Type A Gene

    PubMed Central

    Wróbel-Dudzińska, Dominika; Kosior-Jarecka, Ewa; Łukasik, Urszula; Kocki, Janusz; Witczak, Agnieszka; Mosiewicz, Jerzy; Żarnowski, Tomasz

    2015-01-01

    The aim of the research is to analyse the influence of polymorphisms of endothelin-1 gene and endothelin-1 receptor type A gene on the clinical condition of patients with primary open angle glaucoma. Methods. 285 Polish patients took part in the research (160 normal-tension glaucoma and 125 high-tension glaucoma). DNA was isolated by standard methods and genotype distributions of four polymorphisms in genes encoding endothelin-1 (K198N) and endothelin-1 receptor type A polymorphisms (C1222T, C70G, and G231A) were determined. Genotype distributions were compared between NTG and HTG groups. The clinical condition of participants was examined for association with polymorphisms. Results. A similar frequency of occurrence of the polymorphic varieties of the studied genes was observed in patients with NTG and HTG. There is no relation between NTG risk factors and examined polymorphisms. NTG patients with TT genotype of K198N polymorphism presented with the lowest intraocular pressure in comparison to GG + GT genotype (p = 0.03). In NTG patients with CC genotype of C1222T polymorphism (p = 0.028) and GG of C70G polymorphism (p = 0.03) the lowest values of mean blood pressure were observed. Conclusions. The studied polymorphic varieties (K198N, C1222T) do have an influence on intraocular pressure as well as arterial blood pressure in NTG patients. PMID:26697209

  14. Association between MTHFR gene polymorphisms and the risk of autism spectrum disorders: a meta-analysis.

    PubMed

    Pu, Danhua; Shen, Yiping; Wu, Jie

    2013-10-01

    Methylenetetrahydrofolate reductase (MTHFR) is essential for DNA biosynthesis and the epigenetic process of DNA methylation, and its gene polymorphisms have been implicated as risk factors for birth defects, neurological disorders, and cancers. However, reports on the association of MTHFR polymorphisms with autism spectrum disorders (ASD) are inconclusive. Therefore, we investigated the relationship of the MTHFR polymorphisms (C677T and A1298C) and the risk of ASD by meta-analysis. Up to December 2012, eight case-control studies involving 1672 patients with ASD and 6760 controls were included for meta-analysis. The results showed that the C677T polymorphism was associated with significantly increased ASD risk in all the comparison models [T vs. C allele (frequency of allele): odds ratio (OR) = 1.42, 95% confidence interval (CI): 1.09-1.85; CT vs. CC (heterozygote): OR = 1.48, 95% CI: 1.09-2.00; TT vs. CC (homozygote): OR = 1.86, 95% CI: 1.08-3.20; CT+TT vs. CC (dominant model): OR = 1.56, 95% CI: 1.12-2.18; and TT vs. CC+CT (recessive model): OR = 1.51, 95% CI: 1.02-2.22], whereas the A1298C polymorphism was found to be significantly associated with reduced ASD risk but only in a recessive model (CC vs. AA+AC: OR = 0.73, 95% CI: 0.56-0.97). In addition, we stratified the patient population based on whether they were from a country with food fortification of folic acid or not. The meta-analysis showed that the C677T polymorphism was found to be associated with ASD only in children from countries without food fortification. Our study indicated that the MTHFR C677T polymorphism contributes to increased ASD risk, and periconceptional folic acid may reduce ASD risk in those with MTHFR 677C>T polymorphism. PMID:23653228

  15. CD16 and CD32 Gene Polymorphisms May Contribute to Risk of Idiopathic Thrombocytopenic Purpura.

    PubMed

    Xu, Jiannan; Zhao, Liyun; Zhang, Yan; Guo, Qingxu; Chen, Hui

    2016-01-01

    BACKGROUND Epidemiological studies have evaluated the associations of CD16 158F>V and CD32 131H>R gene polymorphisms with the risk of idiopathic thrombocytopenic purpura (ITP). MATERIAL AND METHODS Published studies on CD16 158F>V and CD32 131H>R polymorphisms with susceptibility to ITP were systematically reviewed until April 1, 2014. The Cochrane Library Database, Medline, CINAHL, EMBASE, Web of Science, and Chinese Biomedical Database (CBM) were used to search for relevant studies and then a meta-analysis was conducted by using Stata 12.0 software in order to produce consistent statistical results. RESULTS In total, 10 clinical case-control studies with 741 ITP patients and 1092 healthy controls were enrolled for quantitative data analysis. Results of this meta-analysis suggest that CD16 158F>V polymorphism had strong correlations with the susceptibility to ITP under 5 genetic models (all P<0.05). However, no similar associations were found between CD32 131H>R polymorphism and the susceptibility to ITP (all P>0.05). Subgroup analysis by ethnicity revealed that CD16 158F>V polymorphism was associated with the increased risk of ITP among both Caucasian and non-Caucasian populations. Nevertheless, no statistically significant correlations between CD32 131H>R polymorphism and the risk of ITP were observed among Caucasians and non-Caucasians (all P>0.05). CONCLUSIONS Our findings indicate that CD16 158F>V polymorphism may contribute to the increased risk of ITP, whereas CD32 131H>R polymorphism may not be an important risk factor for ITP. PMID:27315784

  16. CD16 and CD32 Gene Polymorphisms May Contribute to Risk of Idiopathic Thrombocytopenic Purpura

    PubMed Central

    Xu, Jiannan; Zhao, Liyun; Zhang, Yan; Guo, Qingxu; Chen, Hui

    2016-01-01

    Background Epidemiological studies have evaluated the associations of CD16 158F>V and CD32 131H>R gene polymorphisms with the risk of idiopathic thrombocytopenic purpura (ITP). Material/Methods Published studies on CD16 158F>V and CD32 131H>R polymorphisms with susceptibility to ITP were systematically reviewed until April 1, 2014. The Cochrane Library Database, Medline, CINAHL, EMBASE, Web of Science, and Chinese Biomedical Database (CBM) were used to search for relevant studies and then a meta-analysis was conducted by using Stata 12.0 software in order to produce consistent statistical results. Results In total, 10 clinical case-control studies with 741 ITP patients and 1092 healthy controls were enrolled for quantitative data analysis. Results of this meta-analysis suggest that CD16 158F>V polymorphism had strong correlations with the susceptibility to ITP under 5 genetic models (all P<0.05). However, no similar associations were found between CD32 131H>R polymorphism and the susceptibility to ITP (all P>0.05). Subgroup analysis by ethnicity revealed that CD16 158F>V polymorphism was associated with the increased risk of ITP among both Caucasian and non-Caucasian populations. Nevertheless, no statistically significant correlations between CD32 131H>R polymorphism and the risk of ITP were observed among Caucasians and non-Caucasians (all P>0.05). Conclusions Our findings indicate that CD16 158F>V polymorphism may contribute to the increased risk of ITP, whereas CD32 131H>R polymorphism may not be an important risk factor for ITP. PMID:27315784

  17. Analysis of Polymorphisms in the Lactotransferrin Gene Promoter and Dental Caries

    PubMed Central

    Brancher, João Armando; Pecharki, Giovana Daniela; Doetzer, Andrea Duarte; Medeiros, Kamilla Gabriella dos Santos; Cordeiro Júnior, Carlos Alberto; Sotomaior, Vanessa Santos; Bauer, Peter; Trevilatto, Paula Cristina

    2011-01-01

    Regarding host aspects, there has been strong evidence for a genetic component in the etiology of caries. The salivary protein lactotransferrin (LTF) exhibits antibacterial activity, but there is no study investigating the association of polymorphisms in the promoter region of LTF gene with caries. The objective of this study was firstly to search the promoter region of the human LTF gene for variations and, if existent, to investigate the association of the identified polymorphisms with dental caries in 12-year-old students. From 687 unrelated, 12-year-old, both sex students, 50 individuals were selected and divided into two groups of extreme phenotypes according to caries experience: 25 students without (DMFT = 0) and 25 with caries experience (DMFT ≥ 4). The selection of individuals with extreme phenotypes augments the chances to find gene variations which could be associated with such phenotypes. LTF gene-putative promoter region (+39 to −1143) of the selected 50 individuals was analyzed by high-resolution melting technique. Fifteen students, 8 without (DMFT = 0) and 7 with caries experience (mean DMFT = 6.28), presented deviations of the pattern curve suggestive of gene variations and were sequenced. However, no polymorphisms were identified in the putative promoter region of the LTF gene. PMID:22190933

  18. Polymorphic CUG repeats in human mRNAs and their effects on gene expression.

    PubMed

    Tian, Bin; Mukhopadhyay, Rupa; Mathews, Michael B

    2005-01-01

    Expanded CUG repeats in the 3'-untranslated region (UTR) of the gene encoding myotonic dystrophy protein kinase (DMPK) cause myotonic dystrophy type 1 disease (DM1). The presence of such repeats has been found to impede gene expression at several levels in model systems. We took a bioinformatic approach to survey all human mRNA sequences for polymorphic CUG repeats. Our survey revealed that CUG repeats occur widely in various regions of mRNAs, with higher frequency in protein coding regions than 5'-UTRs or 3'-UTRs. About 30 genes were found to contain CUG repeats that are polymorphic in the number of repeats, suggesting the potential to expand or shrink. However, long polymorphic repeats were restricted to the 3'-UTR of the DMPK gene and the coding region of the ribosomal protein L14 gene. Using cell-free translation systems, we showed that extended CUG repeats can inhibit protein synthesis in vitro in the rabbit reticulocyte lysate, but not in wheat germ extracts, consistent with our previous finding of an interaction of CUG repeats with the protein kinase PKR. In transfected cells, CUG repeats can inhibit gene expression both in cis and in trans. However, observations with PKR-minus cells indicate that these effects are not primarily attributable to the interaction of extended CUG repeats with PKR. Northwestern blotting detected the presence in human cells of more CUG-binding proteins than are currently known. PMID:17114933

  19. Genetic Polymorphisms of Metastasis Suppressor Gene NME1 and Breast Cancer Survival

    PubMed Central

    Qu, Shimian; Long, Jirong; Cai, Qiuyin; Shu, Xiao-Ou; Cai, Hui; Gao, Yu-Tang; Zheng, Wei

    2009-01-01

    Purpose Ample evidence supports an important role of tumor metastasis suppressor genes in cancer metastatic processes. We evaluated the association of genetic polymorphisms of tumor metastasis suppressor gene NME1 with breast cancer prognosis in a follow-up study of patients with primary breast cancer and further investigated the functions of these polymorphisms. Experimental Design NME1 genotypes were analyzed in a cohort of 1134 breast cancer patients recruited as part of the Shanghai Breast Cancer Study who were followed for a median of 7.1 years. In vitro biochemical analyses were carried out to examine the function of NME1 gene polymorphisms. Results Single nucleotide polymorphisms (SNPs) in the promoter region of the NME1 gene were found to be associated with breast cancer prognosis. Patients carrying the C allele in rs16949649 were associated with higher breast cancer-specific mortality (HR =1.4, 95% CI =1.1–1.9) as compared to those carrying the wild-type allele, and the association was more evident in patients with an early stage cancer (HR=1.7, 95% CI =1.2–2.5). SNP rs2302254 was also associated with breast cancer prognosis, and the association was statistically significant for the risk of breast cancer relapse, metastasis, and death (HR=1.3, 95% CI, 1.0–1.6). In vitro biochemical analyses showed that minor alleles in rs2302254 and rs3760468, which is in strong linkage disequilibrium with rs16949646, altered nuclear proteins binding capacity and reduced NME1 promoter activity, supporting the results from an association study of these SNPs with breast cancer survival. Conclusion Promoter polymorphisms in the NME1 gene may alter its expression and influence breast cancer survival. PMID:18676749

  20. Folate and One-Carbon Metabolism Gene Polymorphisms and Their Associations With Oral Facial Clefts

    PubMed Central

    Boyles, Abee L.; Wilcox, Allen J.; Taylor, Jack A.; Meyer, Klaus; Fredriksen, Åse; Ueland, Per Magne; Drevon, Christian A.; Vollset, Stein Emil; Lie, Rolv Terje

    2008-01-01

    Folate metabolism plays a critical role in embryonic development. Prenatal folate supplementation reduces the risk of neural tube defects and probably oral facial clefts. Previous studies of related metabolic genes have associated polymorphisms in cystathionine-beta-synthase (CBS) and 5,10-methylenetetrahydrofolate reductase (MTHFR) with cleft risk. We explored associations between genes related to one-carbon metabolism and clefts in a Norwegian population-based study that included 362 families with cleft lip with or without cleft palate (CL/P) and 191 families with cleft palate only (CPO). We previously showed a 39% reduction in risk of CL/P with folic acid supplementation in this population. In the present study we genotyped 12 polymorphisms in nine genes related to one-carbon metabolism and looked for associations of clefting risk with fetal polymorphisms, maternal polymorphisms, as well as parent-of-origin effects, using combined likelihood-ratio tests (LRT). We also stratified by maternal periconceptional intake of folic acid (>400 μg) to explore gene-exposure interactions. We found a reduced risk of CL/P with mothers who carried the CBS C699T variant (rs234706); relative risk was 0.94 with one copy of the T allele (95% CI 0.63-1.4) and 0.50 (95% CI 0.26-0.96) with two copies (P = 0.008). We found no evidence of interaction of this variant with folate status. We saw no evidence of risk from the MTHFR C677T variant (rs1801133) either overall or after stratifying by maternal folate intake. No associations were found between any of the polymorphisms and CPO. Genetic variations in the nine metabolic genes examined here do not confer a substantial degree of risk for clefts. Published 2008 Wiley-Liss, Inc.† PMID:18203168

  1. Association of I-FABP gene polymorphism and the risk of coronary heart disease

    PubMed Central

    Yuan, Dong; Yu, Changqing; Zeng, Chunyu

    2015-01-01

    Objective: The study aimed to investigate the association between polymorphism of I-FABP gene and coronary heart disease (CHD). Methods: 225 patients with CHD were randomly recruited into the case group, and 196 healthy elderly volunteers were recruited from Medical Examination Center of our hospital as control. General clinical data were collected and plasma TC, TG, LDL-C, HDL-C levels were measured. Besides, polymerase chain reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) technology were used to detect the polymorphism of Hha-I enzyme cleavage sites in I-FABP gene in the study population. Results: Hha-I cleavage sites occurred at codon 54 in exon in the coding sequencing of I-FABP gene in all participants. After cleavage with Hha-I enzyme, the genotypes were identified as wild-type A/A, heterozygous mutant A/T and homozygous mutant T/T. In case group, A/T and T/T genetic carriers had significantly higher levels of TC, TG and LDL-C than A/A carriers (P<0.05). However, in control group, similar differences were not observed (P>0.05). BMI, dietary habits and I-FABP alleles were independent risk factors of CHD. Conclusion: The polymorphism of I-FABP gene existed in the study population. And this genetic variation had influence on lipid metabolism, which was associated with the risk of developing CHD. I-FABP gene polymorphism may contribute to the increased genetic susceptibility to CHD. PMID:26629163

  2. Endothelial nitric oxide synthase gene polymorphism is associated with sickle cell disease patients in India.

    PubMed

    Nishank, Sudhansu Sekhar; Singh, Mendi Prema Shyam Sunder; Yadav, Rajiv; Gupta, Rasik Bihari; Gadge, Vijay Sadashiv; Gwal, Anil

    2013-12-01

    Patients with sickle cell disease (SCD) produce significantly low levels of plasma nitric oxide (NO) during acute vaso-occlusive crisis. In transgenic sickle cell mice, NO synthesized by endothelial nitric oxide synthase (eNOS) enzyme of vascular endothelial cells has been found to protect the mice from vaso-occlusive events. Therefore, the present study aims to explore possible association of eNOS gene polymorphism as a potential genetic modifier in SCD patients. A case control study involving 150 SCD patients and age- and ethnicity-matched 150 healthy controls were genotyped by PCR-restriction fragment length polymorphism techniques for three important eNOS gene polymorphisms-eNOS 4a/b, eNOS 894G>T and eNOS -786T>C. It was observed that SCD patients had significantly higher frequencies of mutant alleles besides heterozygous and homozygous mutant genotypes of these three eNOS gene polymorphisms and low levels of plasma nitrite (NO2) as compared with control groups. The SCD severe group had significantly lower levels of plasma NO2 and higher frequencies of mutant alleles of these three SNPs of eNOS gene in contrast to the SCD mild group of patients. Haplotype analysis revealed that frequencies of one mutant haplotype '4a-T-C' (alleles in order of eNOS 4a/b, eNOS 894G>T and eNOS -786T>C) were significantly high in the severe SCD patients (P<0.0001), whereas the frequency of a wild haplotype '4b-G-T' was found to be significantly high (P<0.0001) in the SCD mild patients, which indicates that eNOS gene polymorphisms are associated with SCD patients in India and may act as a genetic modifier of the phenotypic variation of SCD patients. PMID:24088668

  3. Adiponectin exacerbates collagen-induced arthritis via enhancing Th17 response and prompting RANKL expression.

    PubMed

    Sun, Xiaoxuan; Feng, Xiaoke; Tan, Wenfeng; Lin, Na; Hua, Minhui; Wei, Yu; Wang, Fang; Li, Ningli; Zhang, Miaojia

    2015-01-01

    We previously reported adiponectin (AD) is highly expressed in the inflamed synovial joint tissue and correlates closely with progressive bone erosion in Rheumatoid arthritis (RA) patients. Here, we investigate the role of adiponectin in regulating Th17 response and the expression of receptor activator of nuclear factor-κB ligand (RANKL) in mice with CIA mice by intraarticularly injection of adiponectin into knee joints on day 17, day 20 and day 23 post first collagen immunization. The increased adiponectin expression was found in inflamed joint tissue of collagen-induced arthritis (CIA) mice. Adiponectin injection resulted in an earlier onset of arthritis, an aggravated arthritic progression, more severe synovial hyperplasia, bone erosion and osteoporosis in CIA mice. CD4(+)IL-17(+) Th17 cells, IL-17 mRNA and RANKL mRNA expression were markedly increased in the joint tissue of adiponectin treated CIA mice. Moreover, adiponectin treatment markedly enhanced Th17 cell generation from naive CD4(+) T cells in vitro, which accompanied by the high expression of Th17 transcription factor ROR-γt, and Th17 cytokine genes included IL-22 and IL-23. This study reveals a novel effect of adiponectin in exacerbating CIA progression by enhancing Th17 cell response and RANKL expression. PMID:26063682

  4. Genetic polymorphisms of interleukin genes and the risk of Alzheimer's disease: An update meta-analysis

    PubMed Central

    Mun, Myung-Jin; Kim, Jin-Ho; Choi, Ji-Young; Jang, Won-Cheoul

    2016-01-01

    Objectives Recently, several meta-analyses have reported an association between interleukin (IL) gene polymorphisms and the risk of Alzheimer's disease (AD). Several further papers discussing the relationship with the risk of AD have recently been published. The aim of this meta-analysis was to re-evaluate and update the associations between IL gene polymorphisms and the risk of AD. Methods The search sources were PubMed, Science Direct, Scopus, and Google Scholar up to July 2015, and the following search terms were used: “interleukin 1 or interleukin 6 or interleukin 10” and “variant or polymorphism or SNP” in combination with “Alzheimer's disease”. A meta-analysis using the pooled odds ratios and 95% confidence intervals was carried out to assess the associations between four polymorphisms of IL genes (− 889C > T in IL-1α, − 511C > T in IL-1β, − 174G > C in IL-6 and − 1082G > A in IL-10) and the risk of AD under the heterozygous, homozygous, dominant, and recessive models with fixed- or random-effects models. Results A total of 21,864 cases and 40,321 controls from 93 individual studies were included in this meta-analysis. Our results indicated that the − 889C > T polymorphism was strongly associated with the increased risk of AD. However, three polymorphisms were not associated with the risk of AD. Conclusions Similar to previous meta-analyses, our updated meta-analysis suggested that the − 889C > T polymorphism may be a factor in AD. However, the results of our meta-analysis of the − 174G > C polymorphism differed from those of previous meta-analyses. Consequently, we suggest that the − 174G > C polymorphism may not be a risk factor for AD. PMID:27014584

  5. Porcine NAMPT gene: search for polymorphism, mapping and association studies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    NAMPT encodes for an enzyme catalysing the rate-limiting step in NAD biosynthesis. The extracellular form of the enzyme is known as adipokine visfatin. We detected SNP AM999341:g.669T>C in intron 9 and SNP FN392209:g.358A>G in the promoter of the gene. RH mapping linked the gene to microsatellite SW...

  6. Polymorphisms in the phosducin (PDC) gene on chromosome 1q25-32

    SciTech Connect

    Humphries, P.; Mansergh, F.C.; Farrar, G.J.

    1994-09-01

    Phosducin (33 kDa protein or MEKA) is a principal water-soluble phosphoprotein in the rod and cone photoreceptor cells and pinealocytes. This protein modulates the phototransduction cascade by binding to the beta and gamma subunit complexes of transducin. The PDC gene has been mapped to 1q25-32, the region of linkage of two hereditary retinal degenerative disorders; autosomal dominant juvenile-onset open-angle glaucoma and one form of autosomal recessive RP. Using previously published sequence data, PCR primers were designed to amplify the coding and 5{prime} flanking regions of the PDC gene. Direct sequencing revealed three polymorphisms in the 5{prime} flanking region, two of which were in regions highly homologous between humans and mice. Analysis of the polymorphisms was then extended to larger population samples using SSCPE and denaturing gel analysis. The first polymorphism PDC1 resulted from an insertion of a G residue at position -653/4. Allele frequencies were determined to be 0.51 (insG) and 0.49 (normal) giving a PIC value of 0.50. A deletion of a T residue at position -488 was the basis of the PDC2 polymorphism with allele frequencies of 0.88 (normal) and 0.12 (delT) and a PIC value of 0.21. Interestingly, the allele with an inserted G residue in PDC1 always segregrated with the deleted T allele in PDC2. The third polymorphism PDC3 was caused by a T or G residue at position -1083. Allele frequencies of 0.26 (G residue) and 0.74 (T residue) were determined from an analysis of 80 individuals with an overall PIC value of 0.39. The identification of these three polymorphisms in the PDC gene will be useful for future genetic linkage studies of chromosome 1q in inherited retinopathies.

  7. Protective role of Interleukin 27 (IL-27) gene polymorphisms in patients with ulcerative colitis.

    PubMed

    Yamamoto-Furusho, Jesús K; Posadas-Sánchez, Rosalinda; Alvarez-León, Edith; Vargas-Alarcón, Gilberto

    2016-04-01

    Ulcerative colitis (UC) is a chronic condition of unknown etiology and a polygenic disease. The interleukin 27 (IL-27) have been implicated in the pathogenesis of several autoimmune diseases including inflammatory bowel disease. Several polymorphisms of IL-27 have been associated with several types of cancer and immune disorders. The aim of the present study was to evaluate the association between IL-27 gene polymorphisms and the development of UC. Four polymorphisms of IL-27p28 gene (rs181206, rs26528, rs17855750, and rs40837) and three of the Epstein-Barr virus-induced gene 3 (EBI3) (rs428253, rs4740, and rs4905) were genotyped by 5' exonuclease TaqMan genotyping assays on an ABI Prism 7900HT Fast Real-Time PCR System in 375 Mexican patients with UC and 1599 Mexican Mestizo healthy unrelated individuals. IL-27 levels were determined in 458 healthy controls. Under recessive model adjusted by age and gender, the IL-27p28 rs17855750 polymorphism was associated with decreased risk of developing UC (OR=0.27, 95% CI: 0.06-1.13, P=0.031). On the other hand, under recessive models adjusted by age and gender, the EBI3 rs428253 (OR=0.54, 95% CI: 0.29-0.99, P=0.035), rs4740 (OR=0.60, 95% CI: 0.36-1.01, P=0.046) and rs4905 (OR=0.59, 95% CI: 0.35-1.01, P=0.043) were associated with decreased risk of developing UC. Similar levels of IL-27 were observed among the genotypes of the studied polymorphisms. IL-27 polymorphisms might play a protective role for the development of UC in the Mexican population. PMID:26905929

  8. C10X polymorphism in the CARD8 gene is associated with bacteraemia

    PubMed Central

    Asfaw Idosa, Berhane; Sahdo, Berolla; Balcha, Ermias; Kelly, Anne; Söderquist, Bo; Särndahl, Eva

    2014-01-01

    The NLRP3 inflammasome is an intracellular multi-protein complex that triggers caspase-1 mediated maturation of interleukin-1β (IL-1β); one of the most potent mediators of inflammation and a major cytokine produced during severe infections, like sepsis. However, the excessive cytokine levels seem to stage for tissue injury and organ failure, and high levels of IL-1β correlates with severity and mortality of sepsis. Instead, recent data suggest caspase-1 to function as a guardian against severe infections. CARD8 has been implied to regulate the synthesis of IL-1β via interaction to caspase-1. In recent years, polymorphism of CARD8 (C10X) per se or in combination with NLRP3 (Q705K) has been implicated with increased risk of inflammation. The aim was to investigate the correlation of these polymorphisms with severe blood stream infection. Human DNA was extracted from blood culture bottles that were found to be positive for microbial growth (i.e. patients with bacteraemia). Polymorphisms Q705K in the NLRP3 gene and C10X in the CARD8 gene were genotyped using TaqMan genotyping assay. The results were compared to healthy controls and to samples from patients with negative cultures. The polymorphism C10X was significantly over-represented among patients with bacteraemia as compared to healthy controls, whereas patients with negative blood culture were not associated with a higher prevalence. No association was observed with polymorphism Q705K of NLRP3 in either group of patients. Patients carrying polymorphism C10X in the CARD8 gene are at increased risk of developing bacteraemia and severe inflammation. PMID:25400921

  9. Polymorphic variation in the 11beta-hydroxylase gene associates with reduced 11-hydroxylase efficiency.

    PubMed

    Barr, Marianne; MacKenzie, Scott M; Friel, Elaine C; Holloway, Christine D; Wilkinson, Donna M; Brain, Nick J R; Ingram, Mary C; Fraser, Robert; Brown, Morris; Samani, Nilesh J; Caulfield, Mark; Munroe, Patricia B; Farrall, Martin; Webster, John; Clayton, David; Dominiczak, Anna F; Connell, John M C; Davies, Eleanor

    2007-01-01

    The -344 C/T and intron 2 conversion variants in the CYP11B2 gene, encoding aldosterone synthase, have been associated with markers of impaired 11beta-hydroxylase activity. We hypothesize that this association is because of variations in the adjacent 11beta-hydroxylase gene (CYP11B1) and arises through linkage disequilibrium between CYP11B1 and CYP11B2. The pattern of variation across the entire CYP11B locus was determined by sequencing 26 normotensive subjects stratified by and homozygous for the -344 and intron conversion variants. Eighty-three variants associated with -344 and intron conversion were identified. Haplotype analysis revealed 4 common haplotypes, accounting for 68% of chromosomes, confirming strong linkage disequilibrium across the region. Two novel CYP11B1 polymorphisms upstream of the coding region (-1889 G/T and -1859 A/G) were identified as contributing to the common haplotypes. Given the potential for such mutations to affect transcriptional regulation of CYP11B1, these were analyzed further. A total of 512 hypertensive subjects from the British Genetics of Hypertension Study population were genotyped for these polymorphisms. A significant association was identified between the -1889 polymorphism and urinary tetrahydrodeoxycortisol/total cortisol metabolite ratio, indicating reduced 11beta-hydroxylase efficiency. A similar pattern was observed for the -1859 polymorphism, but this did not achieve statistical significance. Functional studies in vitro using luciferase reporter gene constructs show that these polymorphisms significantly alter the transcriptional response of CYP11B1 to stimulation by adrenocorticotropic hormone or forskolin. This study strongly suggests that the impaired 11beta-hydroxylase efficiency associated previously with the CYP11B2 -344 and intron conversion variants is because of linkage with these newly identified polymorphisms in CYP11B1. PMID:17075029

  10. Genetic Architecture of Plasma Adiponectin Overlaps With the Genetics of Metabolic Syndrome–Related Traits

    PubMed Central

    Henneman, Peter; Aulchenko, Yurii S.; Frants, Rune R.; Zorkoltseva, Irina V.; Zillikens, M. Carola; Frolich, Marijke; Oostra, Ben A.; van Dijk, Ko Willems; van Duijn, Cornelia M.

    2010-01-01

    OBJECTIVE Adiponectin, a hormone secreted by adipose tissue, is of particular interest in metabolic syndrome, because it is inversely correlated with obesity and insulin sensitivity. However, it is not known to what extent the genetics of plasma adiponectin and the genetics of obesity and insulin sensitivity are interrelated. We aimed to evaluate the heritability of plasma adiponectin and its genetic correlation with the metabolic syndrome and metabolic syndrome–related traits and the association between these traits and 10 ADIPOQ single nucleotide polymorphisms (SNPs). RESEARCH DESIGN AND METHODS We made use of a family-based population, the Erasmus Rucphen Family study (1,258 women and 967 men). Heritability analysis was performed using a polygenic model. Genetic correlations were estimated using bivariate heritability analyses. Genetic association analysis was performed using a mixed model. RESULTS Plasma adiponectin showed a heritability of 55.1%. Genetic correlations between plasma adiponectin HDL cholesterol and plasma insulin ranged from 15 to 24% but were not significant for fasting glucose, triglycerides, blood pressure, homeostasis model assessment of insulin resistance (HOMA-IR), and C-reactive protein. A significant association with plasma adiponectin was found for ADIPOQ variants rs17300539 and rs182052. A nominally significant association was found with plasma insulin and HOMA-IR and ADIPOQ variant rs17300539 after adjustment for plasma adiponectin. CONCLUSIONS The significant genetic correlation between plasma adiponectin and HDL cholesterol and plasma insulin should be taken into account in the interpretation of genome-wide association studies. Association of ADIPOQ SNPs with plasma adiponectin was replicated, and we showed association between one ADIPOQ SNP and plasma insulin and HOMA-IR. PMID:20067957

  11. MicroRNA-378 Regulates Adiponectin Expression in Adipose Tissue: A New Plausible Mechanism

    PubMed Central

    Ishida, Masayoshi; Shimabukuro, Michio; Yagi, Shusuke; Nishimoto, Sachiko; Kozuka, Chisayo; Fukuda, Daiju; Soeki, Takeshi; Masuzaki, Hiroaki; Tsutsui, Masato; Sata, Masataka

    2014-01-01

    Aims Mechanisms regulating adiponectin expression have not been fully clarified. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, are involved in biological processes, including obesity and insulin resistance. We evaluated whether the miRNA-378 pathway is involved in regulating adiponectin expression. Methods and Results First, we determined a putative target site for miRNA-378 in the 3 prime untranslated region (3'UTR) of the adiponectin gene by in silico analysis. The levels of adiponectin mRNA and protein were decreased in 3T3-L1 cells overexpressing the mimic of miRNA-378. Luminescence activity in HEK293T cells expressing a renilla-luciferase-adiponectin-3'UTR sequence was inhibited by overexpressing the mimic of miRNA-378, and the decrease was reversed by adding the inhibitor of miRNA-378. Moreover, we confirmed the inhibitory effects of the mimic were cancelled in a deleted mutant of the miR-378 3′-UTR binding site. Addition of tumor necrosis factor-α (TNFα) led a upregulation of miR-378 and downregulation of adiponectin at mRNA and protein levels in 3T3-L1 cells. Level of miR-378 was higher and mRNA level of adiponectin was lower in diabetic ob/ob mice than those of normal C57BL/6 mice and levels of miR378 and adiponectin were negatively well correlated (r = −0.624, p = 0.004). Conclusions We found that levels of miRNA-378 could modulate adiponectin expression via the 3'UTR sequence-binding site. Our findings warrant further investigations into the role of miRNAs in regulating the adiponectin expression. PMID:25379946

  12. [Alzheimer's disease and methylenetetrahydrofolate reductase gene polymorphisms: a potential nutrigenomic approach for Mexico].

    PubMed

    Castillo-Quan, Jorge I; Pérez-Osorio, Julia M

    2009-01-01

    The establishment of medical genomics in Mexico offers the possibility to study in a more comprehensive manner the etiological factors of different diseases, providing a global view of the interaction between the genome and the environment. Nutrition is recognized as a significant determinant in several diseases, yet its interaction with polymorphisms, and in general with the genome, has not been properly addressed Mexico has a high prevalence of polymorphisms of the methylenetetrahydrofolate reductase gene, and in both clinical and basic studies this has been associated with an increased susceptibility of developing Alzheimer's disease. We propose a potential nutrigenomic approach for the study of Alzheimer disease in Mexico. PMID:19518022

  13. Gene polymorphisms potentially related to the pharmacokinetics of clozapine: a systematic review.

    PubMed

    Krivoy, Amir; Gaughran, Fiona; Weizman, Abraham; Breen, Gerome; MacCabe, James H

    2016-07-01

    Clozapine is currently the ultimate effective therapy for otherwise treatment-refractory schizophrenia. However, the drug is also associated with many adverse effects, some of them potentially fatal. Thus, there is an unmet need to predict clinical response to clozapine. As the pharmacokinetics of clozapine vary considerably between and within individuals, there may be an association between genetic polymorphisms and clozapine plasma concentration and consequently, clinical response. We have reviewed studies that have investigated the association between clozapine metabolic pathways related to genes polymorphisms in relation to plasma clozapine concentration and clinical response. Overall, most of the studies reported negative results. The only gene polymorphism that has been found to be associated with clozapine plasma concentration and response was the ABCB1 gene, which codes for transmembrane transporters expressed in the bowel mucosa, blood-brain barrier, kidney and liver. More prospective longitudinal studies are needed to elucidate the possible role of the ABCB1 polymorphism and transmembrane transporters in clozapine pharmacokinetics and clinical response. PMID:25563806

  14. Association of IFNGR2 gene polymorphisms with pulmonary tuberculosis among the Vietnamese.

    PubMed

    Hijikata, Minako; Shojima, Junko; Matsushita, Ikumi; Tokunaga, Katsushi; Ohashi, Jun; Hang, Nguyen T L; Horie, Toru; Sakurada, Shinsaku; Hoang, Nguyen P; Thuong, Pham H; Lien, Luu T; Keicho, Naoto

    2012-05-01

    Interferon-γ (IFN-γ) is a key molecule of T helper 1 (Th1)-immune response against tuberculosis (TB), and rare genetic defects of IFN-γ receptors cause disseminated mycobacterial infection. The aim of the present study was to investigate whether genetic polymorphisms found in the Th1-immune response genes play a role in TB. In our study, DNA samples were collected from two series of cases including 832 patients with new smear-positive TB and 506 unrelated individuals with no history of TB in the general population of Hanoi, Vietnam. Alleles of eight microsatellite markers located around Th1-immune response-related genes and single nucleotide polymorphisms near the promising microsatellites were genotyped. A set of polymorphisms within the interferon gamma receptor 2 gene (IFNGR2) showed a significant association with protection against TB (P = 0.00054). Resistant alleles tend to be less frequently found in younger age at diagnosis (P = 0.011). Luciferase assays revealed high transcriptional activity of the promoter segment in linkage disequilibrium with resistant alleles. We conclude that the polymorphisms of IFNGR2 may confer resistance to the TB development of newly infected individuals. Contribution of the genetic factors to TB appeared to be different depending on age at diagnosis. PMID:22057826

  15. Approaches to evaluating the association of vitamin D receptor gene polymorphisms with breast cancer risk.

    PubMed

    Guy, Michelle; Lowe, Lorraine C; Bretherton-Watt, Deborah; Mansi, Janine L; Colston, Kay W

    2003-01-01

    The steroid hormone 1,25 dihydroxyvitamin D3 is thought to protect against breast cancer. Its actions are mediated via the vitamin D receptor (VDR) and a number of polymorphisms in the VDR gene have been identified, some of which may alter susceptibility to breast cancer. This study has investigated whether specific VDR gene polymorphisms are associated with breast cancer risk in a UK Caucasian population. Female breast cancer patients (n = 313) and control women with a negative screening mammogram (n = 410) were recruited and their VDR polymorphisms were determined. The 3' VDR polymorphism BsmI was significantly associated with breast cancer risk; odds ratio bb vs. BB genotype = 1.79 (95% CI, 1.12-2.86; P = 0.0221). In addition, over 70% of seven commonly used breast cancer cell lines were found to have the at-risk genotype bb. The 5' FokI gene variant was not associated with breast cancer risk. Further investigations into how these different genotypes may affect the functional mechanisms of the VDR will provide a better strategy for identifying women at risk of breast cancer and for developing improved treatments. PMID:12899513

  16. Association of thrombogenic genes polymorphisms with hepatocellular carcinoma in HCV Egyptian patients.

    PubMed

    Hanafy, Amr S; Alaa, Farag A; Randa, Mohamed H

    2016-04-10

    The rate of development of fibrosis varies among HCV patients and affected by many variables. We aimed to investigate the association between mutations in Factor V, prothrombin gene and thrombospondin 1 polymorphisms with hepatic fibrosis progression rate and development of HCC in patients infected with HCV and if they are potential markers for early prediction of disease progression. A total of 280 HCV-infected patients (70 with mild fibrosis, 70 with advanced fibrosis, 70 cirrhotic patients and 70 HCC patients) and 100 healthy controls were included. Factor V Leiden G1691A, prothrombin G20210A and thrombospondin 1 mutations were analyzed by restriction fragment length polymorphism. We observed that there were no significant differences between Factor V Leiden (G1691A) or TPS-1 (A2210G) polymorphisms in the four patient subgroups and control group. In HCC patients, the frequencies of GA genotype were significantly increased compared with control subject. HCV patients carrying GA genotype were more likely to develop hepatocellular carcinoma (OR=5.4, 95% CI=1.09-27.05; P=0.026).We concluded that the risk of HCC was increased 5-fold in subjects carrying GA genotype of prothrombin G20210A gene. However, there was no evidence for a significant association between thrombogenic genes polymorphisms and progression of fibrosis in HCV Egyptian patients. PMID:26768578

  17. Correlation between PON1 gene polymorphisms and breast cancer risk: a Meta-analysis

    PubMed Central

    Wen, Yayuan; Huang, Zemin; Zhang, Xiaohua; Gao, Bo; He, Yujun

    2015-01-01

    Objective: A number of studies have investigated the relationship between the PON1 gene polymorphisms and breast cancer risk, but the conclusions are not consistent. In this paper, a meta-analysis was conducted to explore the possible reasons for these inconsistencies, expecting to further clarify the correlation between PON1 gene polymorphisms and breast cancer risk. Methods: After searches in the database such as MEDLINE, EBSCO, ProQuest, Google Scholar, High-Wire, SID (Scientific Information Database) and PubMed, 7 literatures were collected. RevMan 5.2 software was used to perform the meta-analysis. Random-effects or fixed-effects model was used to analyze the odds ratio (OR) and 95% confidence intervals. Results: The analysis of L55M single nucleotide polymorphisms (SNPs) showed that M allele frequency was positively correlated with the incidence risk of breast cancer (OR=1.34, 95% CI: 1.03-1.74). While we did not found Q192R polymorphism associated with the risk of breast cancer (OR=1.0, 95% CI: 0.71-1.42). Conclusion: For PON1 gene, the frequencies of M allele were associated with the incidence risk of breast cancer. PMID:26884950

  18. Circulating Endocannabinoids and the Polymorphism 385C>A in Fatty Acid Amide Hydrolase (FAAH) Gene May Identify the Obesity Phenotype Related to Cardiometabolic Risk: A Study Conducted in a Brazilian Population of Complex Interethnic Admixture.

    PubMed

    Martins, Cyro José de Moraes; Genelhu, Virginia; Pimentel, Marcia Mattos Gonçalves; Celoria, Bruno Miguel Jorge; Mangia, Rogerio Fabris; Aveta, Teresa; Silvestri, Cristoforo; Di Marzo, Vincenzo; Francischetti, Emilio Antonio

    2015-01-01

    The dysregulation of the endocannabinoid system is associated with cardiometabolic complications of obesity. Allelic variants in coding genes for this system components may contribute to differences in the susceptibility to obesity and related health hazards. These data have mostly been shown in Caucasian populations and in severely obese individuals. We investigated a multiethnic Brazilian population to study the relationships among the polymorphism 385C>A in an endocannabinoid degrading enzyme gene (FAAH), endocannabinoid levels and markers of cardiometabolic risk. Fasting plasma levels of endocannabinoids and congeners (anandamide, 2-arachidonoylglycerol, N-oleoylethanolamide and N-palmitoylethanolamide) were measured by liquid chromatography-mass spectrometry in 200 apparently healthy individuals of both genders with body mass indices from 22.5 ± 1.8 to 35.9 ± 5.5 kg/m2 (mean ± 1 SD) and ages between 18 and 60 years. All were evaluated for anthropometric parameters, blood pressure, metabolic variables, homeostatic model assessment of insulin resistance (HOMA-IR), adiponectin, leptin, C-reactive protein, and genotyping. The endocannabinoid levels increased as a function of obesity and insulin resistance. The homozygous genotype AA was associated with higher levels of anandamide and lower levels of adiponectin versus wild homozygous CC and heterozygotes combined. The levels of anandamide were independent and positively associated with the genotype AA position 385 of FAAH, C-reactive protein levels and body mass index. Our findings provide evidence for an endocannabinoid-related phenotype that may be identified by the combination of circulating anandamide levels with genotyping of the FAAH 385C>A; this phenotype is not exclusive to mono-ethnoracial populations nor to individuals with severe obesity. PMID:26561012

  19. Circulating Endocannabinoids and the Polymorphism 385C>A in Fatty Acid Amide Hydrolase (FAAH) Gene May Identify the Obesity Phenotype Related to Cardiometabolic Risk: A Study Conducted in a Brazilian Population of Complex Interethnic Admixture

    PubMed Central

    Martins, Cyro José de Moraes; Genelhu, Virginia; Pimentel, Marcia Mattos Gonçalves; Celoria, Bruno Miguel Jorge; Mangia, Rogerio Fabris; Aveta, Teresa; Silvestri, Cristoforo; Di Marzo, Vincenzo; Francischetti, Emilio Antonio

    2015-01-01

    The dysregulation of the endocannabinoid system is associated with cardiometabolic complications of obesity. Allelic variants in coding genes for this system components may contribute to differences in the susceptibility to obesity and related health hazards. These data have mostly been shown in Caucasian populations and in severely obese individuals. We investigated a multiethnic Brazilian population to study the relationships among the polymorphism 385C>A in an endocannabinoid degrading enzyme gene (FAAH), endocannabinoid levels and markers of cardiometabolic risk. Fasting plasma levels of endocannabinoids and congeners (anandamide, 2-arachidonoylglycerol, N-oleoylethanolamide and N-palmitoylethanolamide) were measured by liquid chromatography-mass spectrometry in 200 apparently healthy individuals of both genders with body mass indices from 22.5 ± 1.8 to 35.9 ± 5.5 kg/m2 (mean ± 1 SD) and ages between 18 and 60 years. All were evaluated for anthropometric parameters, blood pressure, metabolic variables, homeostatic model assessment of insulin resistance (HOMA-IR), adiponectin, leptin, C-reactive protein, and genotyping. The endocannabinoid levels increased as a function of obesity and insulin resistance. The homozygous genotype AA was associated with higher levels of anandamide and lower levels of adiponectin versus wild homozygous CC and heterozygotes combined. The levels of anandamide were independent and positively associated with the genotype AA position 385 of FAAH, C-reactive protein levels and body mass index. Our findings provide evidence for an endocannabinoid-related phenotype that may be identified by the combination of circulating anandamide levels with genotyping of the FAAH 385C>A; this phenotype is not exclusive to mono-ethnoracial populations nor to individuals with severe obesity. PMID:26561012

  20. Polymorphism in the melatonin receptor gene in buffalo populations of the Brazilian Amazon.

    PubMed

    Machado, E B; Souza, B B; Guimarães, R C; Azevedo, J S N; Gonçalves, E C; Ribeiro, H F L; Rolim Filho, S T; Silva Filho, E

    2016-01-01

    Buffalo farming in Brazil is increasing, as is the challenge of identifying molecular markers that will improve productivity. Therefore, the aim of this study was to analyze single nucleotide polymorphisms of the receptor gene for the hormone melatonin in buffaloes from northern Brazil by polymerase chain reactions (PCRs) and restriction fragment length polymorphism assays. The PCR products exhibited a cutting point for HpaI at the 318th position of the gene, indicating a transition substitution (T↔C). This substitution was synonymic, and did not alter the stability of the mRNA structure. Allelic and genotypic frequencies differed between the populations studied, and all of the populations demonstrated endogamy and were in Hardy-Weinberg equilibrium. Therefore, the HpaI restriction marker in the melatonin receptor gene cannot be used for genetic improvement, but is an excellent marker for population genetic studies. PMID:27173294

  1. Combinations of FUT2 gene polymorphisms and environmental factors are associated with oral cancer risk.

    PubMed

    Su, Kuo-Jung; Ho, Chuan-Chen; Lin, Chiao-Wen; Chen, Mu-Kuan; Su, Shih-Chi; Yu, Yung-Luen; Yang, Shun-Fa

    2016-05-01

    In humans, fucosyltransferase-2 (FUT2) plays an important role in α1,2- linkage of fucose and participates in complex cellular processes such as fertilization, embryogenesis, and immune responses. However, little information is available concerning the FUT2 expression in tumorigenesis. The aim of this work was to investigate the combined effect of FUT2 gene polymorphisms and exposure to environmental carcinogens on the susceptibility and clinic pathological characteristics of oral cancer. Four SNPs of the FUT2 gene (rs281377, rs1047781, rs601338, and rs602662) from 1200 non-cancer controls and 700 oral squamous cell carcinoma (OSCC) patients were analyzed by real-time polymerase chain reaction (PCR). The samples were further analyzed to clarify the associations between these gene polymorphisms and the risk of OSCC, and the impact of these SNPs on the susceptibility and clinic pathological characteristics of OSCC. After adjusting for other covariant, we observed that betel quid chewing among 1255 smokers who carrying at least one C genotype (TC and CC) at rs281377 and least one T genotype (TA and TT) at rs1047781 were exhibited synergistic effects of environmental factors (betel quid and cigarette use) on the susceptibility of oral cancer. Taken together, our results support gene-environment interactions of FUT2 polymorphisms with smoking and betel quid chewing habits possibly altering oral cancer susceptibility. Furthermore, to our knowledge, this is the first study of association between FUT2 gene variants and OSCC risk. PMID:26646561

  2. Exploring polymorphisms and effects of candidate genes on milk fat quality in dairy sheep.

    PubMed

    Crisà, A; Marchitelli, C; Pariset, L; Contarini, G; Signorelli, F; Napolitano, F; Catillo, G; Valentini, A; Moioli, B

    2010-08-01

    The aim of the present study was to investigate the genetic control of the fatty acid (FA) composition in milk from 3 breeds of sheep: Altamurana, Gentile di Puglia, and Sarda. Single nucleotide polymorphisms within genes, encoding enzymes putatively involved in the synthesis and metabolism of milk fat, were selected for analysis, and the allele substitution effects were determined for 16 genes, which were polymorphic in the 3 sheep breeds, upon the milk fat composition. Four genes (alpha-1-antichymotrypsin-2; diacylglycerol O-acyltransferase homolog-2; propionyl Coenzyme A carboxylase, beta polypeptide; and insulin-like growth factor-I) play a role in the desaturation of stearic FA into polyunsaturated fatty acids. Furthermore, 2 genes (growth hormone receptor and zona pellucida glycoprotein-2) affect the variability of the total fat content in addition to the butyric and stearic FA profile, and the fatty acid synthetase gene has an influence on the medium-chain FA. Milk FA profiles play an important role in dairy sheep farming because they have a large effect on cheese characteristics and also because sheep milk may be marketed as a source of nutraceuticals because it contains higher levels of conjugated linoleic acid than milk from other ruminants. The current study evaluated the global effects of a large number of single nucleotide polymorphisms and haplotypes on traits that are not commonly investigated in sheep but that are potentially very useful for improving milk quality. PMID:20655453

  3. Effects of RAGE Gene Polymorphisms on the Risk and Progression of Hepatocellular Carcinoma.

    PubMed

    Su, Shih-Chi; Hsieh, Ming-Ju; Chou, Ying-Erh; Fan, Wen-Lang; Yeh, Chao-Bin; Yang, Shun-Fa

    2015-08-01

    Hepatocellular carcinoma (HCC) is a common malignancy of the liver, whose heterogeneous incidence reflects genetic variations among individuals in the main risk factors. The receptor for advanced glycosylation endproducts (RAGE) is a multiligand receptor and known to be implicated in various pathogenic conditions, such as diabetes, inflammatory disorder, Alzheimer disease, and cancer. In this study, the impact of RAGE gene polymorphisms on the susceptibility to hepatocarcinogenesis was explored. Four single-nucleotide polymorphisms (SNPs), rs184003 (1704G > T), rs1800624 (-374T > A), rs1800625 (-429T > C), and rs2070600 (Gly82Ser), as well as 1 gene polymorphism of RAGE gene, a 63 bp deletion allele (-407 to -345) were analyzed between 300 cancer-free subjects and 265 HCC cases. We detected a significant association of rs1800625 with the increased risk of HCC (odds ratio [OR], 2.565; 95% confidence interval [CI], 1.492-4.409 and adjusted odds ratio [AOR], 2.568; 95% CI, 1.418-4.653). However, patients who possess at least 1 polymorphic allele of rs1800625 are less prone to develop late-stage (stage III/IV, OR, 0.502; 95% CI, 0.243-1.037; P = 0.059 and AOR, 0.461; 95% CI, 0.219-0.970; P = 0.041) and large-size tumors (OR, 0.398; 95% CI, 0.183-0.864; P = 0.017 and AOR, 0.351; 95% CI, 0.157-0.781; P = 0.010). Furthermore, individuals bearing specific haplotypes of 4 RAGE SNPs tested are more inclined to have HCC. In conclusion, our data suggest a correlation of RAGE gene polymorphism rs1800625 with the early stage of liver tumorigenesis and implicate its protective role in the progression of HCC. PMID:26313784

  4. Effect of MDR1 gene polymorphisms on mortality in paraquat intoxicated patients.

    PubMed

    Kim, Hak Jae; Kim, Hyung-Ki; Kwon, Jun-Tack; Lee, Sun-Hyo; El Park, Sam; Gil, Hyo-Wook; Song, Ho-Yeon; Hong, Sae-Yong

    2016-01-01

    Paraquat is a fatal herbicide following acute exposure. Previous studies have suggested that multidrug resistance protein 1 (MDR1) might help remove paraquat from the lungs and the kidney. MDR1 single-nucleotide polymorphisms (SNPs) are involved in the pharmacokinetics of many drugs. The purpose of this study was to determine whether MDR1 SNPs were associated with the mortality in paraquat intoxicated patients. We recruited 109 patients admitted with acute paraquat poisoning. They were genotyped for C1236T, G2677T/A, and C3435T single-nucleotide polymorphisms (SNPs) of MDR1 gene. Their effects on mortality of paraquat intoxicated patients were evaluated. Overall mortality rate was 66.1%. Regarding the C1236T of the MDR1 gene polymorphism, 21 (19.3%) had the wild type MDR1 while 88 (80.7%) had homozygous mutation. Regarding the C3435T MDR1 gene polymorphism, 37(33.9%) patients had the wild type, 23 (21.1%) had heterozygous mutation, and 49 (45.0%) had homozygous mutation. Regarding the G2677T/A MDR1 gene polymorphism, 38 (34.9%) patients had the wild type, 57 (52.3%) had heterozygous mutation, and 14 (12.8%) had homozygous mutation. None of the individual mutations or combination of mutations (two or three) of MDR1 SNP genotypes altered the morality rate. The mortality rate was not significantly different among SNP groups of patients with <4.0 μg/mL paraquat. In conclusion, MDR1 SNPs have no effect on the mortality rate of paraquat intoxicated patients. PMID:27545861

  5. Polymorphisms of IL-10 gene in patients infected with HCV under antiviral treatment in southern Brazil.

    PubMed

    da Silva, Naylê Maria Oliveira; Germano, Fabiana Nunes; Vidales-Braz, Beatris Maria; Carmo Zanella, Ricardo do; dos Santos, Deise Machado; Lobato, Rubens; de Martinez, Ana Maria Barral

    2015-06-01

    Interleukin-10 (IL-10) is a cytokine that plays an important role in the regulation of the immune system. Gene polymorphisms of IL-10 have been associated with the different expression levels of this cytokine. In hepatitis C virus infection, IL-10 appears to interfere with the progression of disease, viral persistence and the response to therapy. This study investigated genetic variability in the IL-10 gene promoter between patients infected with hepatitis C virus (HCV) and healthy individuals, associating the frequency of polymorphisms with different aspects of viral infection. This is a case-control study with 260 patients who were infected with HCV and 260 healthy individuals. Genotyping of the polymorphisms was performed using the technique of amplification refractory mutation system PCR (ARMS-PCR) for regions of the IL-10 gene promoter (-1082 G/A, -819 C/T, -592 C/A). The frequencies of alleles and genotypes related to polymorphisms in the IL-10 gene promoter showed a higher frequency of the G allele and genotype GG in the -1082 region between the infected group and the control group (p=0.005 and p=0.001, respectively), whereas the AA genotype was significantly more frequent in the control group. The frequencies of the haplotypes GTA and GCC were higher in the group of infected individuals, whereas the haplotype ATA was more frequent in the healthy group (p<0.006). It was also observed that the genotypes GG and AG in the region -1082 were significantly more frequent among patients infected with HCV who were in advanced stages of fibrosis and cirrhosis (p=0.042). No association was observed between polymorphisms of IL-10 and sustained virologic response (SVR). PMID:25797191

  6. Association of Vitamin D Receptor Gene Polymorphisms with Colorectal Cancer in a Saudi Arabian Population

    PubMed Central

    Alkhayal, Khayal A.; Awadalia, Zainab H.; Vaali-Mohammed, Mansoor-Ali; Al Obeed, Omar A.; Al Wesaimer, Alanoud; Halwani, Rabih; Zubaidi, Ahmed M.

    2016-01-01

    Background Vitamin D, causally implicated in bone diseases and human malignancies, exerts its effects through binding to the vitamin D receptor (VDR). VDR is a transcription factor modulating the expression of several genes in different pathways. Genetic variants in the VDR gene have been associated with several cancers in different population including colorectal cancer. Objective To assess the association of VDR gene polymorphisms in relation with colorectal cancer (CRC) in a Saudi population. Methods The polymorphisms of VDR gene (BsmI, FokI, ApaI and TaqI) were analyzed by the polymerase chain reaction amplification of segments of interest followed by Sanger sequencing. One hundred diagnosed CRC patients and 100 healthy control subjects that were age and gender matched were recruited. Results We did not observe significant association of any of the four VDR polymorphisms with colorectal cancer risk in the overall analysis. Although not statistically significant, the AA genotype of BsmI conferred about two-fold protection against CRCs compared to the GG genotype. Stratification of the study subjects based on age and gender suggests statistically significant association of CRC with the ‘C’ allele of ApaI in patients >57 years of age at disease diagnosis and BsmI polymorphism in females. In addition, statistically significant differences were observed for the genotypic distributions of VDR-BsmI, ApaI and TaqI SNPs between Saudi Arabian population and several of the International HapMap project populations. Conclusion Despite the absence of correlation of the examined VDR polymorphisms with CRCs in the combined analysis, ApaI and BsmI loci are statistically significantly associated with CRC in elderly and female patients, respectively. These findings need further validation in larger cohorts prior to utilizing these SNPs as potential screening markers for colorectal cancers in Saudi population. PMID:27309378

  7. Effect of MDR1 gene polymorphisms on mortality in paraquat intoxicated patients

    PubMed Central

    Kim, Hak Jae; Kim, Hyung-Ki; Kwon, Jun-Tack; Lee, Sun-hyo; el Park, Sam; Gil, Hyo-Wook; Song, Ho-yeon; Hong, Sae-yong

    2016-01-01

    Paraquat is a fatal herbicide following acute exposure. Previous studies have suggested that multidrug resistance protein 1 (MDR1) might help remove paraquat from the lungs and the kidney. MDR1 single-nucleotide polymorphisms (SNPs) are involved in the pharmacokinetics of many drugs. The purpose of this study was to determine whether MDR1 SNPs were associated with the mortality in paraquat intoxicated patients. We recruited 109 patients admitted with acute paraquat poisoning. They were genotyped for C1236T, G2677T/A, and C3435T single-nucleotide polymorphisms (SNPs) of MDR1 gene. Their effects on mortality of paraquat intoxicated patients were evaluated. Overall mortality rate was 66.1%. Regarding the C1236T of the MDR1 gene polymorphism, 21 (19.3%) had the wild type MDR1 while 88 (80.7%) had homozygous mutation. Regarding the C3435T MDR1 gene polymorphism, 37(33.9%) patients had the wild type, 23 (21.1%) had heterozygous mutation, and 49 (45.0%) had homozygous mutation. Regarding the G2677T/A MDR1 gene polymorphism, 38 (34.9%) patients had the wild type, 57 (52.3%) had heterozygous mutation, and 14 (12.8%) had homozygous mutation. None of the individual mutations or combination of mutations (two or three) of MDR1 SNP genotypes altered the morality rate. The mortality rate was not significantly different among SNP groups of patients with <4.0 μg/mL paraquat. In conclusion, MDR1 SNPs have no effect on the mortality rate of paraquat intoxicated patients. PMID:27545861

  8. Relationship of Volumetric Bone Mineral Density and Structural Parameters with ERα Gene Polymorphisms

    PubMed Central

    Cepollaro, C.; Lauretani, F.; Gozzini, A.; Masi, L.; Falchetti, A.; Monte, F.; Carbonell-Sala, S.; Tanini, A.; Corsi, A.M.; Bandinelli, S.; Ferrucci, L.; Brandi, M.L.

    2009-01-01

    Bone mineral density (BMD) contributes to bone strength, and methods for clinical assessment of bone quality characteristics beyond what can be gathered by BMD are awaited. Peripheral quantitative computed tomography (pQCT) allows for separate assessments of cortical and trabecular bone, providing information on bone geometry. Previous studies examining the relationship between estrogen receptor α (ERα) gene polymorphisms and BMD have been performed in large populations. However, only limited information is available on the possible segregation of ERα gene polymorphisms with bone structural properties. The aim of our study was to evaluate the association of XbaI and PvuII ERα gene polymorphisms with QCT parameters. We studied 900 subjects (541 women, 449 men) participating to the InCHIANTI study. By tibial pQCT we evaluated trabecular volumetric BMD, cortical volumetric BMD, cortical bone area, and cortical thickness (CtTh). Subjects were genotyped for ERα gene PvuII and XbaI polymorphisms. Analysis of variance was used for statistical analysis. Male subjects with PP and XX genotypes had higher geometric parameters, and female subjects with XX and PP genotypes showed higher densitometric parameters than other genotypes; however, the differences did not reach statistical significance. After adjustment for potential confounders, we found a significant (P = 0.002) CtTh difference across PvuII polymorphism in male subjects, with higher CtTh values in PP genotypes with respect to Pp and pp genotypes. These results show a relationship between the presence of the P allele and higher values of CtTh in male subjects, indicating for ERα a role in the control of tibial bone geometry. PMID:17505773

  9. Polymorphism in the 3' untranslated region of the phenylalanine hydroxylase gene detected by enzyme mismatch cleavage: evolution of haplotypes.

    PubMed

    Ramus, S J; Cotton, R G

    1995-12-01

    A polymorphism was identified in 3' untranslated region of the phenylalanine hydroxylase gene using the newly described mutation detection method, enzyme mismatch cleavage. This polymorphism, 1546 G-->A, was linked to three mutations on several haplotype backgrounds. A group of haplotypes was identified as evolving from the one ancestral haplotype on which this base substitution occurred. The possible Celtic or Viking origin of this polymorphism is discussed. PMID:8522340

  10. The tandem-repeat polymorphism of the DC-SIGNR gene in HCV infection.

    PubMed

    Nattermann, J; Ahlenstiel, G; Berg, T; Feldmann, G; Nischalke, H D; Müller, T; Rockstroh, J; Woitas, R; Sauerbruch, T; Spengler, U

    2006-01-01

    The C-type lectin DC-SIGNR has been shown to bind hepatitis C virus (HCV). Here, we analysed the tandem-repeat polymorphism of the DC-SIGNR gene with respect to intraindividual HCV replication. In a cross-sectional comparison HCV-infected patients (n = 430) and healthy subjects (n = 100) were genotyped for the DC-SIGNR polymorphism using PCR. The distribution of DC-SIGNR alleles did not differ significantly between the two groups. However, HCV-infected patients with 5-, 6-, and 7-repeat alleles had higher HCV-RNA levels when compared with carriers of 4- and 9-repeat alleles (P < 0.05). Thus, the DC-SIGNR polymorphism might affect HCV loads supporting the concept that DC-SIGNR contributes to HCV replication efficacy. PMID:16364081

  11. The TOMM40 gene rs2075650 polymorphism contributes to Alzheimer's disease in Caucasian, and Asian populations.

    PubMed

    Huang, Hao; Zhao, Jun; Xu, Biyun; Ma, Xu; Dai, Qiaoyun; Li, Taishun; Xue, Fangjing; Chen, Bingwei

    2016-08-15

    Largescale genome-wide association studies (GWAS) showed that the TOMM40 rs2075650 polymorphism is significantly associated with Alzheimer's disease (AD) in Caucasian ancestry and Asian population. Here, we evaluated this association with large-scale samples from selected 12 studies (N=28,515; 10,358 cases and 18,157 controls) through the PubMed, AlzGene, and Google Scholar. We identified a significant association between rs2075650 and AD with P=0.000, OR=4.178 and 95% CI 1.891-9.228. In subgroup analysis, we identified significant association between rs2075650 polymorphism and AD in both Asian and Caucasians but not mixed populations. Collectively, our analysis shows TOMM40 rs2075650 polymorphism is associated with AD susceptibility in Asian, Caucasian, and mixed populations. We believe that our analysis will be helpful for future genetic researches on AD. PMID:27328316

  12. MDR-1 gene C/T polymorphism in COPD: data from Aegean part of Turkey

    PubMed Central

    Toru, Ümran; Ayada, Ceylan; Genç, Osman; Turgut, Sebahat; Turgut, Günfer; Bulut, İsmet

    2014-01-01

    Objective: Genetic factors, in addition to oxidative stress factors, have been implicated in the development of chronic obstructive pulmonary disease (COPD). Multi-drug resistant-1 (MDR-1) is a gene located on chromosome 7 and the products of this gene protect lung tissue from oxidative stress. We searched the frequency of MDR-1 gene C/T polymorphism in patients with COPD and aimed to explain the association between MDR-1 gene and COPD development. Methods: 47 patients with COPD and 64 healthy control participants were placed in this study. DNAs were extracted from blood samples and MDR-1 amplification of DNA was performed using polymerase chain reaction and enzyme digestion techniques. Results: The frequencies of MDR-1 genotypes were found 17.0% for CC, 51.1% for CT and 31.9% for TT in the COPD group and 39.1% for CC, 53.1% for CT and 7.8% for TT in the control group. The distribution of MDR-1 gene C alleles were found 32.3% in COPD group and 67.7% in control group; T alleles were found 55.1% in COPD group and 44.9% in control group. There was statistically significant difference between the groups for genotype and allele frequency of MDR-1 gene (P = 0.001). Conclusion: TT genotype of MDR-1 gene was significantly more frequent in COPD patients. MDR-1 gene C/T polymorphism may play a role in COPD development. PMID:25419400

  13. The Association between MTHFR Gene Polymorphisms and Hepatocellular Carcinoma Risk: A Meta-Analysis

    PubMed Central

    Deng, Yan; Huang, Shan; Xu, Juanjuan; Li, Haiwei; Li, Shan; Zhao, Jinmin

    2013-01-01

    Background The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and hepatocellular carcinoma (HCC) risk was inconsistent and underpowered. To clarify the effects of MTHFR gene polymorphisms on the risk of HCC, a meta-analysis of all available studies relating C677T and/or A1298C polymorphisms of MTHFR gene to the risk of HCC was conducted. Methods The authors searched PubMed, EMBASE, Cochrane Library, Web of Science, and Chinese Biomedical Literature database (CBM) for the period up to July 2012. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Metaregression and subgroup analyses were performed to identify the source of heterogeneity. Results Finally, 12 studies with 2,351 cases and 4,091 controls were included for C677T polymorphism and 6 studies with 1,333 cases and 1,878 controls were included for A1298C polymorphism. With respect to A1298C polymorphism, significantly decreased HCC risk was found in the overall population (CC vs. AA: OR = 0.660, 95%CI 0.460–0.946, P = 0.024; recessive model: OR = 0.667, 95%CI = 0.470–0.948, P = 0.024). In subgroup analyses, significantly decreased HCC risk was found in Asian population (CC vs. AA: OR = 0.647, 95%CI = 0.435–0.963; P = 0.032) and population-based studies (CC vs. AA: OR = 0.519, 95%CI = 0.327–0.823; P = 0.005). With respect to C677T polymorphism, no significant association with HCC risk was demonstrated in overall and stratified analyses. Conclusions We concluded that MTHFR A1298C polymorphism may play a protective role in the carcinogenesis of HCC. Further large and well-designed studies are needed to confirm this association. PMID:23457501

  14. Complement factor H gene polymorphisms and Chlamydia pneumoniae infection in age-related macular degeneration

    PubMed Central

    Haas, P; Steindl, K; Schmid-Kubista, KE; Aggermann, T; Krugluger, W; Hageman, GS; Binder, S

    2014-01-01

    Purpose To investigate the association of the complement factor H gene (CFH) Y402H polymorphism and age-related macular degeneration (AMD) in the Austrian population (Caucasoid descent), and to determine whether there is an association between exposure to Chlamydia pneumoniae—responsible for up to 20% of community-acquired pneumoniae—and the AMD-associated CFH risk polymorphism. Methods Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis in 75 unrelated AMD patients and compared with 75 healthy, age-matched control subjects. C. pneumoniae serum IgG was tested by ELISA (R&D) in both groups. The association between the CFH Y402H genetic polymorphism and the disease was examined by χ2-test and logistic regression. Results CFH Y402H genotype frequencies differed significantly between AMD patients and healthy controls (1277 TT, 22.7%; 1277 TC, 53.3%; and 1277 CC, 22.7% in the AMD group; 1277 TT, 48.0%; 1277 TC, 38.7%; and 1277 CC, 13.3% in the control group) showing a P-value <0.005 (OR:2.920/3.811). No association was found between a positive C. pneumoniae titre and AMD (P = 0.192), nor was any association found between C. pneumoniae and the CFH Y402H polymorphism. Conclusions Our data confirm that the CFH Y402H polymorphism is a risk factor for AMD in the Austrian population with a higher frequency of the Y402 polymorphism in AMD patients. No association between preceding C. pneumoniae infection and diagnosed AMD was found. PMID:19169230

  15. Association between CTLA-4 gene polymorphism and ankylosing spondylitis: a case-control study

    PubMed Central

    Wang, Nai-Guo; Wang, Da-Chuan; Tan, Bing-Yi; Wang, Feng; Yuan, Ze-Nong

    2015-01-01

    Aims: The aim of our study was to evaluate the association between CTLA-4 polymorphisms (+49A/G, -318C/T and CT60A/G) and ankylosing spondylitis (AS) susceptibility. Methods: A total of 120 AS cases and healthy controls, matched on the age and gender, were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) were used to determine the gentypes of +49A/G, -318C/T and CT60A/G polymorphisms. Genotype distribution in control group was assessed by Hardy Weinberg Equilibrium (HWE) test. Odds ratio (OR) with 95% confidence interval (95% CI) were adopted to evaluate the relationship of CTLA-4 polymorphisms and AS susceptibility. Results: In our study, genotype distribution of the three polymorphisms in control group was consistent with the HWE (P > 0.05). The genotype analysis showed that AA genotype of + 49A/G polymorphism could increase the risk for AS (OR=2.357, 95% CI=1.127-4.930). Moreover, the frequency of A allele was also presented as a risk factor for AS. Additionally, AA genotype and A allele of CT60A/G appeared to be related with AS susceptibility (OR=2.610, 95% CI=1.047-6.510; OR=1.751, 95% CI=1.160-2.641). However, the T allele of -318C/T appeared to be a protective factor for AS (OR=0.383, 95% CI=0.228-0.643). Conclusion: In summary, there existed significant association between CTLA-4 gene polymorphisms and increased or decreased risk for AS. PMID:26261646

  16. DNA repair gene ERCC1 polymorphisms may contribute to the risk of glioma.

    PubMed

    Yuan, Guanqian; Gao, Dandan; Ding, Shaofeng; Tan, Jun

    2014-05-01

    Polymorphisms in excision repair cross-complementing rodent repair deficiency complementation group 1 (ERCC1) gene have been shown to affect individual susceptibility to glioma, though studies have yielded conflicting results. This meta-analysis aims to derive a more precise estimation of the association between ERCC1 C8092A and C118T polymorphisms and glioma risk. A literature search of PubMed, Embase, Web of Science, Cochrane Library, and CBM databases was conducted to identify all eligible studies published before August 5, 2013. Crude odds ratios (ORs) with their corresponding confidence intervals (95% CIs) were used to assess the strength of this association. A meta-analysis was performed by reviewing seven studies on the C8092A polymorphism (2,978 cases and 4,051 controls) and four studies on the C118T polymorphism (1,390 Asian cases and 1,546 Asian controls). Pooled analysis yielded a significant association between the C8092A variant genotype and increased risk of glioma. As for ethnicity, the A allele was associated with increased risk of glioma in Asians, while no similar finding was observed in Caucasians. Stratified analyses by histological subtype indicated that the C8092A polymorphism showed a significant association with the risk of non-glioblastoma multiforme. For the C118T polymorphism, increased glioma susceptibility was also observed among Asians. Taken together, results from our meta-analysis support the view that common variants in ERCC1 may contribute to susceptibility to glioma, especially in Asians. However, further studies investigating the significance of these two polymorphisms as markers of susceptibility to and disease progression of glioma are still needed. PMID:24453030

  17. Association of RAGE gene polymorphisms with sporadic Parkinson's disease in Chinese Han population.

    PubMed

    Gao, Jing; Teng, Jijun; Liu, Hongxin; Han, Xun; Chen, Biao; Xie, Anmu

    2014-01-24

    Previous studies have corroborated receptor for advanced glycation end-products (RAGE) ablation had a protective effect on nigral dopaminergic neurons in the MPTP model of Parkinson's disease (PD). Genetic variation of RAGE gene may be associated with the development of onset of sporadic PD. The present study aimed to explore the possible association of RAGE gene polymorphisms namely -374T/A,-429T/C, and G82S with PD. A total of 285 PD patients and 285 healthy-matched individuals in Chinese Han population were enrolled. Genotype analyses were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Only the -429T/C polymorphism denoted a significant difference between PD patients and controls (P=0.015) of the three examined single nucleotide polymorphisms (SNPs). Our data also revealed that -429C allele carriers seem to have a decreased risk of PD (OR=0.617, P=0.007). Moreover, there were significant differences in genotype distribution in female PD group and its healthy-matched control subgroup (P=0.014), as well as between late-onset PD (LOPD) and the controls subgroup (P=0.016). However, for -374T/A and 82GS polymorphisms, there was no significant difference in the genotype and allele frequencies between PD patients and the controls, as well as gender- and age-related differences. Our present findings indicate that the RAGE -429T/C polymorphism may be associated with the susceptibility of PD and the CC genotype of -429T/C may be a protective factor for PD in Chinese Han population. PMID:24304868

  18. Impact of VEGF-C Gene Polymorphisms and Environmental Factors on Oral Cancer Susceptibility in Taiwan

    PubMed Central

    Chien, Ming-Hsien; Liu, Yu-Fan; Hsin, Chung-Han; Lin, Chien-Huang; Shih, Chun-Han; Yang, Shun-Fa; Cheng, Chao-Wen; Lin, Chiao-Wen

    2013-01-01

    Background Oral cancer, which is the fourth most common male cancer, is associated with environmental carcinogens in Taiwan. Vascular endothelial growth factor (VEGF)-C, an angiogenic/lymphangiogenic factor with high expression levels in tumor tissues, plays important roles in the development of several malignancies. This study was designed to examine associations of five VEGF-C gene polymorphisms with the susceptibility to and clinicopathological characteristics of oral squamous cell carcinoma. Methodology/Principal Findings Five single-nucleotide polymorphisms (SNPs) of VEGF-C were analyzed by a real-time polymerase chain reaction (PCR) in 470 male patients with oral cancer and 426 cancer-free controls. In this study, we found that the VEGF-C rs7664413 and rs2046463 polymorphisms were associated with oral-cancer susceptibility but not with any clinicopathological parameters. The GGACA or GACTG haplotype of five VEGF-C SNPs (rs3775194, rs11947611, rs1485766, rs7664413, and rs2046463) combined was also related to the risk of oral cancer. Among 611 male smokers, VEGF-C polymorphism carriers who also chewed betel quid were found to have a 14.5–24.2-fold risk of having oral cancer compared to the VEGF-C wild-type carrier who did not chew betel quid. Among 461 male betel-quid chewers, VEGF-C polymorphism carriers who also smoked had a 2.7–18.1-fold risk of having oral cancer compared to those who carried the wild type but did not smoke. Conclusions Our results suggest that the two SNPs of VEGF-C (rs7664413 and rs2046463) and either of two haplotypes of five SNPs combined have potential predictive significance in oral carcinogenesis. Gene-environmental interactions among VEGF-C polymorphisms, smoking, and betel-quid chewing might alter one's susceptibility to oral cancer. PMID:23593187

  19. Association of Genetic Polymorphisms in TNF and MIF Gene with the Risk of Primary Dysmenorrhea.

    PubMed

    Dogru, Hatice Yilmaz; Ozsoy, Asker Zeki; Karakus, Nevin; Delibas, Ilhan Bahri; Isguder, Cigdem Kunt; Yigit, Serbulent

    2016-08-01

    Primary dysmenorrhea, which affects 90 % of adolescent girls and more than 50 % of menstruating women worldwide, is characterized by recurrent pain during menses in the absence of a detectable organic disease. The aim of this study is to assess the association between MIF -173 and TNF -308 genetic polymorphisms and the clinical features of primary dysmenorrhea. The study population comprised 154 unrelated female patients with clinical diagnosis of dysmenorrhea, and a total of 144 control subjects were recruited consecutively. The MIF -173G > C promoter polymorphism (rs755622) and TNF gene -308G > A (rs1800629) polymorphism were analyzed by polymerase chain reaction-based restriction fragment length polymorphism assay. Two fragments (268 and 97 bp) were seen when the G allele was present at position -173, and three fragments (206, 97, and 62 bp) were observed when the C allele was present. Two fragments (87 and 20 bp) were seen when G allele was present at position -308. There were statistically significant associations between age at menarche and history of back pain among dysmenorrhea patients and MIF gene -173G > C polymorphism (p = 0.003 and p = 0.042, respectively). The genotype and allele frequencies of -308G > A polymorphism showed statistically significant differences between dysmenorrhea patients and controls (p = 0.023 and p = 0.009, respectively). A high association was also observed when the patients were compared with the controls according to the GG genotype versus GA+AA genotypes (p = 0.009). The present study showed that the TNF-α -308 GG genotype may be a useful tool to predict the susceptibility of dysmenorrhea. PMID:27105877

  20. Detection of Cytotoxic T-Lymphocyte Associated Antigen-4 Gene Polymorphism in Type 1 Diabetes Mellitus.

    PubMed

    Arafa, Roshdan M; Desouky, Somaya M; Emam, Sherin M; Abed, Neveen Tawfik; Mohamed, Sahar Y

    2015-01-01

    Type 1 diabetes is one of the most common chronic childhood illnesses. Interplay between genetic susceptibility and environmental factors is thought to provide the fundamental element for the disease. It has been shown that more than 40 genetic loci are associated with T1DM. Important one among these is the CTLA-4. This work aimed to detect Cytotoxic T Lymphocyte-associated antigen 4 (CTLA-4) gene polymorphism in patients with type 1 diabetes mellitus T1DM using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to clarify its role in the susceptibility to T1DM. The study was carried out on forty unrelated Egyptian children with TIDM. Twenty unrelated healthy children were enrolled as a control group. Blood samples were collected from patients and control groups and subjected to CTLA-4 gene polymorphism analysis using polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP). CTLA-4 G allele and GG homozygous genotype were significantly increased in T1DM patients than in control group (P < 0.001, P = 0.002 respectively). There was significant association between the three CTLA-4 genotypes (AA, AG, GG) and diabetic complications (p = 0.002), AG and GG polymorphisms were associated with complications of diabetes with ratio 84.6% and 100% respectively. While no association was found with sex, weight, height, risk factors of diabetes or insulin treatment. It was concluded that there is a strong association between AG polymorphism and T1DM (P = 0.002). PMID:26415372

  1. G-protein-coupled estrogen receptor-30 gene polymorphisms are associated with uterine leiomyoma risk

    PubMed Central

    Kasap, Burcu; Turhan, Nilgün Öztürk; Edgünlü, Tuba; Duran, Müzeyyen; Akbaba, Eren; Öner, Gökalp

    2016-01-01

    The G-protein-coupled estrogen receptor, GPER-1) is a member of the G-protein-coupled receptor 1 family and is expressed significantly in uterine leiomyomas. To understand the relationship between GPR30 single nucleotide polymorphisms and the risk of leiomyoma, we measured the follicle-stimulating hormone (FSH) and estradiol (E2) levels of 78 perimenopausal healthy women and 111 perimenopausal women with leiomyomas. The participants’ leiomyoma number and volume were recorded. DNA was extracted from whole blood with a GeneJET Genomic DNA Purification Kit. An amplification-refractory mutation system polymerase chain reaction approach was used for genotyping of the GPR30 gene (rs3808350, rs3808351, and rs11544331). The differences in genotype and allele frequencies between the leiomyoma and control groups were calculated using the chi-square (χ2) and Fischer’s exact test. The median FSH level was higher in controls (63 vs. 10 IU/L, p=0.000), whereas the median E2 level was higher in the leiomyoma group (84 vs. 9.1 pg/mL, p=0.000). The G allele of rs3808351 and the GG genotype of both the rs3808350 and rs3808351 polymorphisms and the GGC haplotype increased the risk of developing leiomyoma. There was no significant difference in genotype frequencies or leiomyoma volume. However, the GG genotype of the GPR30 rs3808351 polymorphism and G allele of the GPR30 rs3808351 polymorphism were associated with the risk of having a single leiomyoma. Our results suggest that the presence of the GG genotype of the GPR30 rs3808351 polymorphism and the G allele of the GPR30 rs3808351 polymorphism affect the characteristics and development of leiomyomas in the Turkish population. PMID:26773178

  2. Effect of metallothionein 2A gene polymorphism on allele-specific gene expression and metal content in prostate cancer

    SciTech Connect

    Krześlak, Anna; Forma, Ewa; Jóźwiak, Paweł; Szymczyk, Agnieszka; Bryś, Magdalena

    2013-05-01

    Metallothioneins (MTs) are highly conserved, small molecular weight, cysteine rich proteins. The major physiological functions of metallothioneins include homeostasis of essential metals Zn and Cu and protection against cytotoxicity of heavy metals. The aim of this study was to determine whether there is an association between the − 5 A/G single nucleotide polymorphism (SNP; rs28366003) in core promoter region and expression of metallothionein 2A (MT2A) gene and metal concentration in prostate cancer tissues. MT2A polymorphism was determined by the polymerase chain reaction–restriction fragment length polymorphism technique (PCR–RFLP) using 412 prostate cancer tissue samples. MT2A gene expression analysis was performed by real-time RT-PCR method. A significant association between rs28366003 genotype and MT2A expression level was found. The average mRNA level was found to be lower among minor allele carriers (the risk allele) than average expression among homozygotes for the major allele. Metal levels were analyzed by flamed atomic absorption spectrometer system. Highly statistically significant associations were detected between the SNP and Cd, Zn, Cu and Pb levels. The results of Spearman's rank correlation showed that the expressions of MT2A and Cu, Pb and Ni concentrations were negatively correlated. On the basis of the results obtained in this study, we suggest that SNP polymorphism may affect the MT2A gene expression in prostate and this is associated with some metal accumulation. - Highlights: • MT2A gene expression and metal content in prostate cancer tissues • Association between SNP (rs28366003) and expression of MT2A • Significant associations between the SNP and Cd, Zn, Cu and Pb levels • Negative correlation between MT2A gene expression and Cu, Pb and Ni levels.

  3. Polymorphisms within the promoter and the intron 2 of the serotonin transporter gene in a population of bulimic patients.

    PubMed

    Lauzurica, N; Hurtado, A; Escartí, A; Delgado, M; Barrios, V; Morandé, G; Soriano, J; Jáuregui, I; González-Valdemoro, M I; García-Camba, E; Fuentes, J A

    2003-12-11

    The serotonin transporter (5-HTT) gene is a firm candidate to explain eating disorders. In this association study, two different polymorphisms were analysed: a variable number of tandem repeat (VNTR) polymorphism in intron 2 and a deletion/insertion polymorphism (5-HTTLPR) in the promoter region. The hypothesis that these gene polymorphisms may be a susceptibility factor in bulimia nervosa (BN) was explored in a female population of 102 purgative bulimics. BN patients who have suffered preceding anorexia nervosa (AN) episodes formed the so-called previous AN bulimic patient group. In our sample of normal-eater controls and purging type bulimics, regardless of whether or not the BN patients had suffered prior AN episodes, no differences were found considering the frequencies of genotypes, alleles or haplotypes of both polymorphic regions of the 5-HTT gene. PMID:14625025

  4. Chicken TAP genes differ from their human orthologues in locus organisation, size, sequence features and polymorphism.

    PubMed

    Walker, Brian A; van Hateren, Andrew; Milne, Sarah; Beck, Stephan; Kaufman, Jim

    2005-05-01

    We have previously shown that in the chicken major histocompatibility complex, the two transporters associated with antigen processing genes (TAP1 and TAP2) are located head to head between two classical class I genes. Here we show that the region between these two TAP genes has transcription factor-binding sites in common with class I gene promoters. The TAP genes are also up-regulated by interferon-gamma in a similar way to mammalian TAP genes and in a way that suggests they are both transcribed from a bi-directional promoter. The gene structures of TAP1 and TAP2 differ from that of human TAPs in that TAP1 has a truncated exon 1 and TAP2 has fused exons, resulting in a much smaller gene size. The truncation of TAP1 results in the loss of approximately 150 amino acids, which are thought to be involved in endoplasmic reticulum retention, heterodimer formation and tapasin binding, compared to human TAP1. Most of the protein sequence features involved in binding ATP are conserved, with two exceptions: chicken TAP1 has a glycine in the switch region where other TAPs have glutamine or histidine, and both chicken TAP genes have serines in the C motif where mammalian TAP2 has an alanine. Lastly, the chicken TAP genes are highly polymorphic, with at least as many TAP alleles as there are class I alleles, as seen by investigating nine inbred lines of chicken. The close proximity of the TAP genes to the class I genes and the high level of polymorphism may allow co-evolution of the genes, allowing TAP molecules to transport peptides specifically for the class I molecules of that haplotype. PMID:15900495

  5. Frequency of mutations and polymorphisms in borderline ovarian tumors of known cancer genes.

    PubMed

    Stemke-Hale, Katherine; Shipman, Kristy; Kitsou-Mylona, Isidora; de Castro, David G; Hird, Vicky; Brown, Robert; Flanagan, James; Gabra, Hani; Mills, Gordon B; Agarwal, Roshan; El-Bahrawy, Mona

    2013-04-01

    Borderline ovarian tumors represent an understudied subset of ovarian tumors. Most studies investigating aberrations in borderline tumors have focused on KRAS/BRAF mutations. In this study, we conducted an extensive analysis of mutations and single-nucleotide polymorphisms (SNPs) in borderline ovarian tumors. Using the Sequenom MassArray platform, we investigated 160 mutations/polymorphisms in 33 genes involved in cell signaling, apoptosis, angiogenesis, cell cycle regulation and cellular senescence. Of 52 tumors analyzed, 33 were serous, 18 mucinous and 1 endometrioid. KRAS c.35G>A p.Gly12Asp mutations were detected in eight tumors (six serous and two mucinous), BRAF V600E mutations in two serous tumors, and PIK3CA H1047Y and PIK3CA E542K mutations in a serous and an endometrioid BOT, respectively. CTNNB1 mutation was detected in a serous tumor. Potentially functional polymorphisms were found in vascular endothelial growth factor (VEGF), ABCB1, FGFR2 and PHLPP2. VEGF polymorphisms were the most common and detected at four loci. PHLPP2 polymorphisms were more frequent in mucinous as compared with serous tumors (P=0.04), with allelic imbalance in one case. This study represents the largest and most comprehensive analysis of mutations and functional SNPs in borderline ovarian tumors to date. At least 25% of borderline ovarian tumors harbor somatic mutations associated with potential response to targeted therapeutics. PMID:23174937

  6. Risk of open angle glaucoma due to tumor necrosis factor alpha gene polymorphisms

    PubMed Central

    Hamid, Mona Abdel; Moemen, Leqaa; Labib, Hany; Helmy, Hazem; Elsergany, Tarek

    2016-01-01

    Introduction Axonal degeneration and retinal ganglion cell apoptosis in glaucoma is associated with tumor necrosis factor alpha (TNF-α), which is an important pro-inflammatory cytokine. The aim of this study was to determine the association between the risk of open angle glaucoma (OAG) in the Egyptian population and tumor necrosis factor alpha (TNF-α) gene polymorphisms. Methods Sixty OAG patients and 26 healthy unrelated controls were used to analyze TNF-α polymorphism G-308A using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Results the GG genotype was found at a higher frequency in the controls than in the patients, and the AA and GA genotypes were associated strongly with OAG. Conclusion In this study, we found that the TNF-α polymorphism G-308A was associated significantly with OAG in the Egyptian population. However, there is a need for population-based studies with large numbers of subjects. Also, long-term follow up is required to verify the association between TNF-α polymorphism G-308A and glaucoma susceptibility. PMID:27054008

  7. A Delta-Sarcoglycan Gene Polymorphism as a Risk Factor for Hypertrophic Cardiomyopathy

    PubMed Central

    Garrido-Garduño, Martín H.; Pérez-Martínez, Ramón A.; Ruiz, Victor M.; Herrera-Tepatlán, Esteban; Rodríguez-Cruz, Maricela; Jiménez-Vaca, Ana L.; Minauro-Sanmiguel, Fernando; Salamanca-Gómez, Fabio A.

    2012-01-01

    Background: The C allele of c.−94C>G polymorphism of the delta-sarcoglycan gene was associated as a risk factor for coronary spasm in Japanese patients with hypertrophic cardiomyopathy (HCM). Aim: We evaluated whether the c.−94C>G polymorphism can be a risk factor for HCM in Mexican patients. Methods: The polymorphism was genotyped and the risk was estimated in 35 HCM patients and 145 healthy unrelated individuals. Data of this polymorphism reported in Mexican Amerindian populations were included. Results: The C allele frequency in HCM patients was higher with an odds ratio (OR) of 2.37, and the risk for the CC genotype increased to 5.0. The analysis with Mexican Amerindian populations showed that the C allele frequency was significantly higher in HCM patients with an OR of 2.96 and for CC genotype the risk increased to 7.60. Conclusions: The C allele of the c.−94C>G polymorphism is a risk factor for HCM, which is increased by the Amerindian component and can play an important role in the etiology and progression of disease in Mexican patients. PMID:22524166

  8. Associations between matrix metalloproteinase gene polymorphisms and the development of cerebral infarction.

    PubMed

    Zhao, J H; Xu, Y M; Xing, H X; Su, L L; Tao, S B; Tian, X J; Yan, H Q; Ji, S B

    2015-01-01

    The aim of this study was to investigate the association between MMP3 rs3025058 and MMP9 rs3918242 polymorphisms and the development of ischemic stroke in a Chinese population. Between May 2013 and January 2015, 335 patients with ischemic stroke and 335 health control subjects were enrolled in this study. The MMP3 rs3025058 and MMP9 rs3918242 polymorphisms were analyzed using polymerase chain reaction coupled with restriction fragment length polymorphism. By multivariate logistic regression analysis, the CC genotype of MMP9 rs3918242 was shown to be associated with a significantly increased risk of ischemic stroke when compared with the TT genotype [OR (95%CI) = 5.47 (2.64-12.38)]. The TC+CC genotype of MMP9 rs3918242 was furthermore found to be associated with an elevated risk of ischemic stroke in higher BMI individuals [OR (95%CI) = 1.81 (1.03-3.22)]. The findings of this study suggest that the MMP9 rs3918242 polymorphism is associated with an elevated risk of ischemic stroke and that this gene polymorphism interacts with BMI in the risk of ischemic stroke. PMID:26782596

  9. Low-Dose Aspirin-Associated Upper and Mid Gastrointestinal Tract Damage and Gene Polymorphism.

    PubMed

    Shiotani, Akiko; Fujita, Yoshihiko; Nishio, Kazuto

    2015-01-01

    The risk of gastrointestinal (GI) bleeding is increased in association with the use of low-dose aspirin (LDA). There are few studies of the association between genetic polymorphisms and the risks of aspirin-induced ulcer or its complications. Individuals with two single nucleotide polymorphisms (SNPs) of cyclooxygenase-1 (COX-1), A-842G and C50T, exhibit increased sensitivity to aspirin and lower prostaglandin synthesis capacity but the polymorphism lacked statistical significance in relation to an association with bleeding peptic ulcer. In our previous Japanese study, SLCO1B1 521TT genotype and the SLCO1B1 *1b haplotype were significantly associated with the risk of peptic ulcer and ulcer bleeding in patients taking LDA, especially in the patients with angiotensin converting enzyme inhibitor (ACEI), angiotensin type 1 receptor blocker (ARB), or statin co-treatment. Protonpump inhibitors (PPIs) are recommended for patients who require antiplatelet therapy and have a history of upper GI bleeding. The interaction between PPIs and consequent impaired effectiveness of clopidogrel has caused concern regarding the effect of genetic polymorphisms of the CYP2C19 which mediates conversion of clopidogrel to its active metabolite. The later recent genome-wide analysis of SNPs indicated the association of several SNPs with small bowel bleeding in Japanese patients taking LDA. The data are still lacking and further prospective studies are needed to identify the specific gene polymorphisms as risk or protective factors for GI bleeding associated with LDA. PMID:26369686

  10. Association between XPG gene polymorphisms and development of gastric cancer risk in a Chinese population.

    PubMed

    Feng, Y B; Fan, D Q; Yu, J; Bie, Y K

    2016-01-01

    We conducted a case-control study to investigate the role of three common single nucleotide polymorphisms (SNPs) in the xeroderma pigmentosum complementation group G (XPG) gene (rs2094258, rs751402 and rs17655) in the development of gastric cancer in a Chinese population. Between January 2012 and December 2014, samples from a total of 177 patients with gastric cancer and 237 control subjects were collected from the Ankang City Central Hospital. XPG rs2094258, rs751402 and rs17655 polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Using logistic regression analysis, we found that the CC genotype of rs17655 was associated with an elevated risk of gastric cancer, and the adjusted odds ratio (OR) and 95% confidence intervals (95%CI) were 1.91 and 1.07-3.41, respectively. Moreover, individuals carrying the GC + CC genotype of rs17655 had an increased susceptibility to gastric cancer (OR = 1.61, 95%CI = 1.03-2.54). However, we did not observe a significant association between XPG rs2094258 and rs751402 polymorphisms and development of gastric cancer. In conclusion, our study suggests that the rs17655 polymorphism in XPG is associated with an increased risk of gastric cancer. The results of our findings should be further validated by further large sample size studies. PMID:27323165

  11. C677T (RS1801133 ) MTHFR gene polymorphism frequency in a colombian population

    PubMed Central

    Gómez-Gutierrez, Alberto; Gómez, Piedad Elena; Casas-Gomez, Maria Consuelo; Briceño, Ignacio

    2015-01-01

    Introduction: Abnormal levels of the enzyme methylenetetrahydrofolate reductase (MTHFR) are associated with an increased risk of both cardiovascular and cerebrovascular disease and higher concentrations of homocysteine. Abnormal levels are also related to birth defects, pregnancy complications, cancer and toxicity to methotrexate (MTX). Polymorphisms of MTHFR affect the activity of the enzyme. Genetic associations have been related to treatment efficacy. Objective: To establish the frequency of the C> T polymorphism at nucleotide 677 of the MTHFR gene in a group of Colombian individuals. Methods: Data from pharmacogenetic microarrays that include MTX sensibility-associated polymorphisms were retrospectively collected (Pathway Genomics®). The frequency of the C> T MTHFR rs1801133 marker polymorphism was analyzed. Results: Microarray data from 68 men and 84 women were analyzed. Comparisons of genotype C/C vs. C/T and T/T were statistically significantly different (p= 0.00, p= 0.026, respectively), as were C/T and T / T (p= 0.0001). Conclusions: Results for the C/C and C/T genotypes in a Colombian population are similar to other previously studied groups of healthy subjects. Subjects from our population might be at risk of developing diseases associated with MTHFR polymorphisms and might present toxicity and adverse effects if treated with MTX, which suggests the need to evaluate therapeutic alternatives based on individual pharmacogenetic studies. PMID:26309343

  12. The human BARX2 gene: genomic structure, chromosomal localization, and single nucleotide polymorphisms.

    PubMed

    Hjalt, T A; Murray, J C

    1999-12-15

    The BARX genes 1 and 2 are Bar class homeobox genes expressed in craniofacial structures during development. In this report, we present the genomic structure, chromosomal localization, and polymorphic markers in BARX2. The gene has four exons, ranging in size from 85 to 1099 bp. BARX2 is localized on human chromosome 11q25, as determined by radiation hybrid mapping. In the mouse, Barx2 is coexpressed with Pitx2 in several tissues. Based on the coexpression, BARX2 was assumed to be a candidate gene for those cases of Rieger syndrome that cannot be associated with mutations of PITX2. Mutations in PITX2 cause some cases of Rieger syndrome, an autosomal dominant disorder affecting eyes, teeth, and umbilicus. DNA from Rieger patients was subjected to single-strand conformation polymorphism screening of the BARX2 coding region. Three single nucleotide polymorphisms were found in a normal population, although no etiologic mutations were detectable in over 100 cases of Rieger syndrome or in individuals with related ocular disorders. PMID:10644443

  13. Vitamin D gene pathway polymorphisms and risk of colorectal, breast, and prostate cancer.

    PubMed

    McCullough, Marjorie L; Bostick, Roberd M; Mayo, Tinisha L

    2009-01-01

    Higher vitamin D exposure is hypothesized to prevent several cancers, possibly through genomic effects modulated by the vitamin D receptor (VDR), and autocrine/paracrine metabolism of the VDR's ligand, 1alpha,25-(OH)(2)-vitamin D. Herein we review the background and evidence to date on associations between polymorphisms in VDR and selected genes in the vitamin D pathway in relation to colorectal, breast, and prostate cancer. Although most studies to date have examined only a few VDR polymorphisms, more are beginning to comprehensively investigate polymorphisms in the VDR as well as in other vitamin D pathway genes, such as the vitamin D-binding protein gene (Gc) and CYP27B1 and CYP24A1, which code for enzymes that, respectively, synthesize and degrade 1alpha,25-(OH)(2)-vitamin D. Currently, there is no strong, consistent epidemiologic evidence for substantial influences of single variants in vitamin D pathway genes on risk for colorectal, breast, or prostate cancer, but promising leads are developing. PMID:19400699

  14. Effect of leptin gene polymorphisms on growth, slaughter and meat quality traits of grazing Brangus steers.

    PubMed

    Corva, P M; Fernández Macedo, G V; Soria, L A; Papaleo Mazzucco, J; Motter, M; Villarreal, E L; Schor, A; Mezzadra, C A; Melucci, L M; Miquel, M C

    2009-01-01

    Leptin is a hormone that affects the regulation of feed intake, energy balance and body composition in mammals. Several polymorphisms in the bovine leptin gene have been associated with phenotypic variance of these traits. We evaluated two known single nucleotide polymorphisms (SNPs) in the leptin gene of 253 grazing Brangus steers. Brangus is a 5/8 Angus-3/8 Brahman composite. Data were collected during two consecutive growth/fattening cycles from two farms in southeast Buenos Aires province, Argentina. One of the markers is in the promoter region of the gene (SNP1) and the other is a non-synonymous polymorphism in exon 2 (SNP2). The traits that we evaluated were live weight gain in the spring, gain in backfat thickness in the spring, final live weight, final ultrasound backfat thickness, final ultrasound rib eye area, carcass weight and length, carcass yield, kidney fat, kidney fat percentage, backfat thickness, rib eye area, and intramuscular fat percentage. Both markers affected some meat traits; though the only significant associations were of SNP1 with ultrasound rib eye area and of SNP2 with carcass yield and backfat thickness. Under the same conditions as in the present study, leptin markers could be of help only as part of a larger genotyping panel including other relevant genes. PMID:19283678

  15. Polymorphism and genetic mapping of the human oxytocin receptor gene on chromosome 3

    SciTech Connect

    Michelini, S.; Urbanek, M.; Goldman, D.

    1995-06-19

    Centrally administered oxytocin has been reported to facilitate affiliative and social behaviors, in functional harmony with its well-known peripheral effects on uterine contraction and milk ejection. The biological effects of oxytocin could be perturbed by mutations occurring in the sequence of the oxytocin receptor gene, and it would be of interest to establish the position of this gene on the human linkage map. Therefore we identified a polymorphism at the human oxytocin receptor gene. A portion of the 3{prime} untranslated region containing a 30 bp CA repeat was amplified by polymerase chain reaction (PCR), revealing a polymorphism with two alleles occurring with frequencies of 0.77 and 0.23 in a sample of Caucasian CEPH parents (n = 70). The CA repeat polymorphism we detected was used to map the human oxytocin receptor to chromosome 3p25-3p26, in a region which contains several important genes, including loci for Von Hippel-Lindau disease (VHL) and renal cell carcinoma. 53 refs., 2 figs., 1 tab.

  16. The association between sex-related interleukin-6 gene polymorphisms and the risk for cerebral palsy

    PubMed Central

    2014-01-01

    Background The relationship between genetic factors and the development of cerebral palsy (CP) has recently attracted much attention. Polymorphisms in the genes encoding proinflammatory cytokines have been shown to be associated with susceptibility to perinatal brain injury and development of CP. Interleukin-6 (IL-6) is a proinflammatory cytokine that plays a pivotal role in neonatal brain injury, but conflicting results have been reported regarding the association between IL-6 single nucleotide polymorphisms (SNPs) and CP. The purpose of this study was to analyze IL-6 gene polymorphisms and protein expression and to explore the role of IL-6 in the Chinese CP population. Methods A total of 753 healthy controls and 713 CP patients were studied to detect the presence of five SNPs (rs1800796, rs2069837, rs2066992, rs2069840, and rs10242595) in the IL-6 locus. Of these, 77 healthy controls and 87 CP patients were selected for measurement of plasma IL-6 by Luminex assay. The SHEsis program was used to analyze the genotyping data. For all comparisons; multiple testing on each individual SNP was corrected by the SNPSpD program. Results There were no differences in allele or genotype frequencies between the overall CP patients and controls among the five genetic polymorphisms. However, subgroup analysis found significant sex-related differences in allele and genotype frequencies. Differences were found between spastic CP and controls in males for rs2069837; between CP with periventricular leukomalacia and controls in males for rs1800796 and rs2066992; and between term CP and controls in males for rs2069837. Plasma IL-6 levels were higher in CP patients than in the controls, and this difference was more robust in full-term male spastic CP patients. Furthermore, the genotype has an effect on IL-6 synthesis. Conclusions The influence of IL-6 gene polymorphisms on IL-6 synthesis and the susceptibility to CP is related to sex and gestational age. PMID:24903966

  17. Association between ERAP1 gene polymorphisms and ankylosing spondylitis susceptibility in Han population

    PubMed Central

    Wang, Jian; Li, Hang; Wang, Jianwei; Gao, Xiang

    2015-01-01

    Purposes: The present study was designed to investigate the relationship between endoplasmic reticulum amino peptidase 1 (ERAP1) gene polymorphisms and ankylosing spondylitis (AS) in Han population of Shaanxi province. Methods: 100 AS patients and 100 healthy people were enrolled in present study as case and control groups respectively, and the control group was matched with the case group by age and gender. ERAP1 gene rs27434 and rs7711564 polymorphisms were test by TaqMan probe genotyping method. SHEsis software was used to operate linkage disequilibrium (LD) and haplotype analysis between the two single nucleotide polymorphisms (SNPs). χ2 test was employed to compare the differences of the genotype, allele and haplotype frequencies between the case and control groups. Relative risk of AS was represented by odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: In ERAP1 rs27434 and rs7711564 polymorphisms, the frequencies of AA and CC genotypes in case group were significantly higher compared to those in control group (P=0.036; P=0.039), and so were the frequencies of A and C alleles (OR=1.589, 95% CI=1.070-2.359, P=0.028; OR=1.535, 95% CI=1.021-2.308, P=0.050). Linkage disequilibrium test and haplotype analysis of the alleles of the two SNPs showed that the frequency of A-C haplotype was higher in case group than that in control group (P=0.005), which indicated that A-C might be the susceptible haplotype to AS. Conclusions: ERAP1 gene rs27434 and rs7711564 polymorphisms may increase the risk of AS. PMID:26617903

  18. Bactericidal Permeability Increasing Protein Gene Polymorphism is Associated with Inflammatory Bowel Diseases in the Turkish Population

    PubMed Central

    Can, Güray; Akın, Hakan; Özdemir, Filiz T.; Can, Hatice; Yılmaz, Bülent; Eren, Fatih; Atuğ, Özlen; Ünsal, Belkıs; Hamzaoğlu, Hülya O.

    2015-01-01

    Background/Aims: Inflammatory bowel disease, a chronic inflammatory disease with unknown etiology, affects the small and large bowel at different levels. It is increasingly considered that innate immune system may have a central position in the pathogenesis of the disease. As a part of the innate immune system, bactericidal permeability increasing protein has an important role in the recognition and neutralization of gram-negative bacteria. The aim of our study was to investigate the involvement of bactericidal permeability increasing protein gene polymorphism (bactericidal permeability increasing protein Lys216Glu) in inflammatory bowel disease in a large group of Turkish patients. Patients and Methods: The present study included 528 inflammatory bowel disease patients, 224 with Crohn's disease and 304 with ulcerative colitis, and 339 healthy controls. Results: Bactericidal permeability increasing protein Lys216Glu polymorphism was found to be associated with both Crohn's disease and ulcerative colitis (P = 0.0001). The frequency of the Glu/Glu genotype was significantly lower in patients using steroids and in those with steroid dependence (P = 0.012, OR, 0.80; 95% confidence interval [CI]: 0.68-0.94; P = 0.0286, OR, 0.75; 95% CI: 0.66-0.86, respectively). There was no other association between bactericidal permeability increasing protein gene polymorphism and phenotypes of inflammatory bowel disease. Conclusions: Bactericidal permeability increasing protein Lys216Glu polymorphism is associated with both Crohn's disease and ulcerative colitis. This is the first study reporting the association of bactericidal permeability increasing protein gene polymorphism with steroid use and dependence in Crohn's disease. PMID:26228368

  19. Evidence for polymorphism in the cytochrome P450 2D50 gene in horses.

    PubMed

    Corado, C R; McKemie, D S; Young, A; Knych, H K

    2016-06-01

    Metabolism is an essential factor in the clearance of many drugs and as such plays a major role in the establishment of dosage regimens and withdrawal times. CYP2D6, the human orthologue to equine CYP2D50, is a drug-metabolizing enzyme that is highly polymorphic in humans leading to widely differing levels of metabolic activity. As CYP2D6 is highly polymorphic, in this study it was hypothesized that the gene coding for the equine orthologue, CYP2D50, may also be prone to polymorphism. Blood samples were collected from 150 horses, the CYP2D50 gene was cloned and sequenced; and full-length sequences were analyzed for single nucleotide polymorphisms (SNPs), deletions, or insertions. Pharmacokinetic data were collected from a subset of horses following the administration of a single oral dose of tramadol and probit analysis used to calculate metabolic ratios. Prior to drug administration, the ability of recombinant CYP2D50 to metabolize tramadol to O-desmethyltramadol was confirmed. Sequencing of CYP2D50 identified 126 exonic SNPs, with 31 of those appearing in multiple horses. Oral administration of tramadol to a subset of these horses revealed variable metabolic ratios (tramadol: O-desmethyltramadol) in individual horses and separation into three metabolic groups. While a limited number of horses of primarily a single breed were studied, the variability in tramadol metabolism to O-desmethyltramadol between horses and preliminary evidence of what appears to be poor, extensive, and ultra-rapid metabolizers supports further study of the potential for genetic polymorphisms in the CYP2D50 gene in horses. PMID:26441153

  20. Genetic association of cyclooxygenase-2 gene polymorphisms with Parkinson’s disease susceptibility in Chinese Han population

    PubMed Central

    Dai, Yi; Wu, Yuquan; Li, Yansheng

    2015-01-01

    Objective: The aim of this study was to explore the genetic association of cyclooxygenase-2 (COX2) gene promoter region polymorphisms with Parkinson’s disease (PD) susceptibility in Chinese Han population. Methods: The genotyping of COX2 gene polymorphisms was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 122 patients with PD and 120 healthy persons. The association strength of gene polymorphism with disease was measured by odds ratio (OR) and 95% confidence interval (95% CI) calculated using χ2 test which also evaluated the Hardy-Weinberg equilibrium (HWE) of gene polymorphism in controls. The linkage disequilibrium and haplotype were also analyzed as evidence in the analysis of association. Results: On condition that the genotypes distributions of COX2 -1290A>G, -1195G>A, -765G>C in the control group all conformed to HWE, however, only the homozygous genotype AA of -1195G>A polymorphism showed an association with PD (OR=0.432, 95% CI=0.196-0.950). In addition, in haplotype analysis, G-A-C haplotype frequency in cases was significantly lower than the controls, compared with the common haplotype A-G-G (P=0.031, OR=0.375, 95% CI=0.149-0.940). Conclusions: COX2 -1195G>A polymorphism might play a protective role in the onset of PD and G-A-C haplotype in this three promoter region polymorphisms also showed a negative association. PMID:26722563

  1. A COMMON POLYMORPHISM IN THE METHYLENETETRAHYDROFOLATE REDUCTASE (MTHFR) GENE IS ASSOCIATED WITH QUANTITATIVE ULTRASOUND IN THOSE WITH LOW PLASMA FOLATE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A study of a polymorphism in the MTHFR gene, plasma folate, and bone phenotypes in 1632 individuals revealed that the genotype effect on BMD and quantitative ultrasound was dependent on the level of folate. Our findings support the hypothesis that the association between an MTHFR polymorphism and bo...

  2. Identification of Polymorphisms in the Enhancer Region of the Bovine Prolactin Gene and Association with Fertility in Beef Cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives were to investigate the polymorphic nature of the enhancer region of the bovine prolactin (PRL) gene and determine the association of these polymorphisms with fertility in beef cows. Primers were designed to amplify a 500 base pair fragment 892 to 1392 bases upstream of the bovine PRL gen...

  3. The effects of polymorphisms in 7 candidate genes on resistance to Salmonella Enteritidis in native chickens.

    PubMed

    Tohidi, R; Idris, I B; Malar Panandam, J; Hair Bejo, M

    2013-04-01

    Salmonella enterica serovar Enteritidis infection is a common concern in poultry production for its negative effects on growth as well as food safety for humans. Identification of molecular markers that are linked to resistance to Salmonella Enteritidis may lead to appropriate solutions to control Salmonella infection in chickens. This study investigated the association of candidate genes with resistance to Salmonella Enteritidis in young chickens. Two native breeds of Malaysian chickens, namely, Village Chickens and Red Junglefowl, were evaluated for bacterial colonization after Salmonella Enteritidis inoculation. Seven candidate genes were selected on the basis of their physiological role in immune response, as determined by prior studies in other genetic lines: natural resistance-associated protein 1 (NRAMP1), transforming growth factor β3 (TGFβ3), transforming growth factor β4 (TGFβ4), inhibitor of apoptosis protein 1 (IAP1), caspase 1 (CASP1), lipopolysaccharide-induced tumor necrosis factor (TNF) α factor (LITAF), and TNF-related apoptosis-inducing ligand (TRAIL). Polymerase chain reaction-RFLP was used to identify polymorphisms in the candidate genes; all genes exhibited polymorphisms in at least one breed. The NRAMP1-SacI polymorphism correlated with the differences in Salmonella Enteritidis load in the cecum (P = 0.002) and spleen (P = 0.01) of Village Chickens. Polymorphisms in the restriction sites of TGFβ3-BsrI, TGFβ4-MboII, and TRAIL-StyI were associated with Salmonella Enteritidis burden in the cecum, spleen, and liver of Village Chickens and Red Junglefowl (P < 0.05). These results indicate that the NRAMP1, TGFβ3, TGFβ4, and TRAIL genes are potential candidates for use in selection programs for increasing genetic resistance against Salmonella Enteritidis in native Malaysian chickens. PMID:23472012

  4. Oxytocin and Vasopressin Receptor Gene Polymorphisms: Role in Social and Psychiatric Traits

    PubMed Central

    Aspé-Sánchez, Mauricio; Moreno, Macarena; Rivera, Maria Ignacia; Rossi, Alejandra; Ewer, John

    2016-01-01

    Oxytocin (OXT) and arginine-vasopressin (AVP) are two phylogenetically conserved neuropeptides that have been implicated in a wide range of social behaviors. Although a large body of research, ranging from rodents to humans, has reported on the effects of OXT and AVP administration on affiliative and trust behaviors, and has highlighted the genetic contributions of OXT and AVP receptor polymorphisms to both social behaviors and to diseases related to social deficits, the consequences of peptide administration on psychiatric symptoms, and the impact of receptor polymorphisms on receptor function, are still unclear. Despite the exciting advances that these reports have brought to social neuroscience, they remain preliminary and suffer from the problems that are inherent to monogenetic linkage and association studies. As an alternative, some studies are using polygenic approaches, and consider the contributions of other genes and pathways, including those involving DA, 5-HT, and reelin, in addition to OXT and AVP; a handful of report are also using genome-wide association studies. This review summarizes findings on the associations between OXT and AVP receptor polymorphism, social behavior, and psychiatric diseases. In addition, we discuss reports on the interactions of OXT and AVP receptor genes and genes involved in other pathways (such as those of dopamine, serotonin, and reelin), as well as research that has shed some light on the impact of gene polymorphisms on the volume, connectivity, and activation of specific neural structures, differential receptor expression, and plasma levels of the OXT and AVP peptides. We hope that this effort will be helpful for understanding the studies performed so far, and for encouraging the inclusion of other candidate genes not explored to date. PMID:26858594

  5. Oxytocin and Vasopressin Receptor Gene Polymorphisms: Role in Social and Psychiatric Traits.

    PubMed

    Aspé-Sánchez, Mauricio; Moreno, Macarena; Rivera, Maria Ignacia; Rossi, Alejandra; Ewer, John

    2015-01-01

    Oxytocin (OXT) and arginine-vasopressin (AVP) are two phylogenetically conserved neuropeptides that have been implicated in a wide range of social behaviors. Although a large body of research, ranging from rodents to humans, has reported on the effects of OXT and AVP administration on affiliative and trust behaviors, and has highlighted the genetic contributions of OXT and AVP receptor polymorphisms to both social behaviors and to diseases related to social deficits, the consequences of peptide administration on psychiatric symptoms, and the impact of receptor polymorphisms on receptor function, are still unclear. Despite the exciting advances that these reports have brought to social neuroscience, they remain preliminary and suffer from the problems that are inherent to monogenetic linkage and association studies. As an alternative, some studies are using polygenic approaches, and consider the contributions of other genes and pathways, including those involving DA, 5-HT, and reelin, in addition to OXT and AVP; a handful of report are also using genome-wide association studies. This review summarizes findings on the associations between OXT and AVP receptor polymorphism, social behavior, and psychiatric diseases. In addition, we discuss reports on the interactions of OXT and AVP receptor genes and genes involved in other pathways (such as those of dopamine, serotonin, and reelin), as well as research that has shed some light on the impact of gene polymorphisms on the volume, connectivity, and activation of specific neural structures, differential receptor expression, and plasma levels of the OXT and AVP peptides. We hope that this effort will be helpful for understanding the studies performed so far, and for encouraging the inclusion of other candidate genes not explored to date. PMID:26858594

  6. Association between SIRT1 Gene Polymorphisms and Breast Cancer in Egyptians

    PubMed Central

    Rizk, Sherine M.; Shahin, Nancy N.; Shaker, Olfat G.

    2016-01-01

    Background Breast cancer is reported to cause the highest mortality among female cancer patients. Previous studies have explored the association of silent mating-type information regulator 2 homolog 1 (SIRT1) gene expression with prognosis in breast cancer. However, no studies exist, so far, on the role of SIRT1 gene polymorphism in breast cancer risk or prognosis. The present study aimed to assess the association between SIRT1 gene polymorphisms and breast cancer in Egyptians. Methods The study comprised 980 Egyptian females divided into a breast cancer group (541 patients) and a healthy control group (439 subjects). SIRT1 gene single nucleotide polymorphisms (SNPs) rs3758391, rs3740051 and rs12778366 were genotyped using real-time polymerase chain reaction (RT-PCR). Allelic and genotypic frequencies were determined in both groups and association with breast cancer and clinicopathological characteristics was assessed. Results Breast cancer patients exhibited elevated serum SIRT1 levels which varied among different tumor grades. SIRT1 rs3758391 and rs12778366 TT genotypes were more frequent, exhibited higher SIRT1 levels than CC and CT genotypes and were associated with histologic grade and lymph node status. SIRT1 rs12778366 TT genotype also correlated with negative estrogen receptor (ER) and progesterone receptor (PR) statuses. The T allele frequency for both SNPs was higher in breast cancer patients than in normal subjects. Combined GG and AG genotypes of rs3740051 were more frequent, showed higher serum SIRT1 levels than the AA genotype, and were associated with ER and PR expression. Furthermore, inheritance of the G allele was associated with breast cancer. Conclusions Our findings reveal that rs3758391 and rs12778366 polymorphisms of SIRT1 gene are associated with breast cancer risk and prognosis in the Egyptian population. PMID:26999517

  7. Polymorphisms of genes encoding interleukin-4 and its receptor in Iranian patients with juvenile idiopathic arthritis.

    PubMed

    Ziaee, Vahid; Rezaei, Arezou; Harsini, Sara; Maddah, Marzieh; Zoghi, Samaneh; Sadr, Maryam; Moradinejad, Mohammad Hassan; Rezaei, Nima

    2016-08-01

    As cytokines, including interleukin-4 (IL-4), seem to have a pivotal role in the pathogenesis of juvenile idiopathic arthritis (JIA), this study is aimed at investigating of association of polymorphisms in IL-4 and IL-4 receptor α (IL-4RA) genes with susceptibility to JIA. A case-control study was conducted on 53 patients with JIA and 139 healthy unrelated controls. Single nucleotide polymorphisms of IL-4 gene at positions -1098, -590, and -33, as well as IL-4RA gene at position +1902 were genotyped using polymerase chain reaction with sequence-specific primers method and compared between patients and healthy individuals. At the allelic level, C allele at IL-4 -33 was found to be more frequent in patients compared to control (P value <0.01). At the genotypic level, CC genotype at IL-4 -590 (P value <0.01), together with CC and TT genotypes at IL-4 -33 (P value <0.01), were significantly higher in patients with JIA, while TC genotypes at IL-4 -590 and -33 positions were found to be lower in case group (P value <0.01). At the haplotypic level, IL-4 (positions -1098, -509, -33) TTC, GCC, and TTT haplotypes were significantly lower than controls (P value <0.01, P value = 0.03, and P value = 0.04, respectively). Although, TCC haplotype at the same positions was found to be higher in patients (P value <0.01). Polymorphic site of +1902 IL-4RA gene did not differ between cases and controls. Polymorphisms in promoter region of IL-4 but not IL-4RA genes confer susceptibility to JIA and may predispose individuals to adaptive immune responses. PMID:26951255

  8. Association of CD44 Gene Polymorphism with Survival of NSCLC and Risk of Bone Metastasis

    PubMed Central

    Liu, Yaosheng; Qing, Haifeng; Su, Xiuyun; Wang, Cheng; Li, Zhuo; Liu, Shubin

    2015-01-01

    Background Previous studies have reported CD44 expression influenced the development and progression of tumors. The aim of this study was to investigate whether single-nucleotide polymorphisms (SNPs) of the CD44 gene are associated with survival of non-small cell lung cancer (NSCLC) and occurrence rate of bone metastasis. Material/Methods A total of 234 patients with NSCLC between 2003 and 2010 were enrolled in this study and 468 healthy persons were used as controls. Two polymorphisms, rs13347 and rs187115, in the CD44 gene were genotyped using DNA from blood lymphocytes. For statistical analysis we used the chi-square test, Fisher’s exact test, Kaplan-Meier method, and log-rank test. Results CD44 gene rs13347 polymorphism was not associated with NSCLC risk. For rs187115, the association with NSCLC risk was observed (P<0.001). Allele G carriers had significantly higher occurrence rates of bone metastasis (OR=0.4, 95%CI: 0.20–0.64, P<0.001) and more advanced tumor stage (OR=2.6, 95%CI: 1.50–4.45, P=0.001) compared to carriers of allele A. The survival rates for patients with AA genotype were significantly higher than for patients with the AG+GG genotypes (P<0.001). In multivariate analysis of survival in NSCLC patients, significant predictors were CD44 gene (AG+GG) (RR=0.48, 95%CI: 0.34–0.68, P<0.001), tumor stage (RR=0.45, 95%CI: 0. 0.31–0.65, P<0.001), and bone metastasis (RR=1.52, 95%CI: 1.05–2.21, P=0.027). Conclusions CD44 gene rs187115 polymorphism is a potential predictive marker of survival in NSCLC patients, and is significantly correlated with bone metastasis and tumor stage. PMID:26356590

  9. Impacts of CA9 Gene Polymorphisms on Urothelial Cell Carcinoma Susceptibility and Clinicopathologic Characteristics in Taiwan

    PubMed Central

    Ou, Yen-Chuan; Chen, Chuan-Shu; Li, Jian-Ri; Yang, Shun-Fa

    2013-01-01

    Background Carbonic anhydrase 9 (CA9) is reportedly overexpressed in several types of carcinomas and is generally considered a marker of malignancy. The current study explored the effect of CA9 gene polymorphisms on the susceptibility of developing urothelial cell carcinoma (UCC) and the clinicopathological status. Methodology and Principal Findings A total of 442 participants, including 221 healthy people and 221 patients with UCC, were recruited for this study. Four single-nucleotide polymorphisms (SNPs) of the CA9 gene were assessed by a real-time PCR with the TaqMan assay. After adjusting for other co-variants, the individuals carrying at least one A allele at CA9 rs1048638 had a 2.303-fold risk of developing UCC than did wild-type (CC) carriers. Furthermore, UCC patients who carried at least one A allele at rs1048638 had a higher invasive stage risk (p< 0.05) than did patients carrying the wild-type allele. Moreover, among the UCC patients with smoker, people with at least one A allele of CA9 polymorphisms (rs1048638) had a 4.75-fold (95% CI = 1.204–18.746) increased risk of invasive cancer. Conclusion The rs1048638 polymorphic genotypes of CA9 might contribute to the prediction of susceptibility to and pathological development of UCC. This is the first study to provide insight into risk factors associated with CA9 variants in carcinogenesis of UCC in Taiwan. PMID:24349364

  10. The influence of BMX gene polymorphisms on clinical symptoms after mild traumatic brain injury.

    PubMed

    Wang, Yu-Jia; Hsu, Yu-Wen; Chang, Che-Mai; Wu, Chung-Che; Ou, Ju-Chi; Tsai, Yan-Rou; Chiu, Wen-Ta; Chang, Wei-Chiao; Chiang, Yung-Hsiao; Chen, Kai-Yun

    2014-01-01

    Mild traumatic brain injury (mTBI) is one of the most common neurological disorders. Most patients diagnosed with mTBI could fully recover, but 15% of patients suffer from persistent symptoms. In recent studies, genetic factors were found to be associated with recovery and clinical outcomes after TBI. In addition, results from our previous research have demonstrated that the bone marrow tyrosine kinase gene in chromosome X (BMX), a member of the Tec family of kinases, is highly expressed in rats with TBI. Therefore, our aim in this study was to identify the association between genetic polymorphisms of BMX and clinical symptoms following mTBI. Four tagging single nucleotide polymorphisms (tSNPs) of BMX with minimum allele frequency (MAF) >1% were selected from the HapMap Han Chinese database. Among these polymorphisms, rs16979956 was found to be associated with the Beck anxiety inventory (BAI) and dizziness handicap inventory (DHI) scores within the first week after head injury. Additionally, another SNP, rs35697037, showed a significant correlation with dizziness symptoms. These findings suggested that polymorphisms of the BMX gene could be a potential predictor of clinical symptoms following mTBI. PMID:24860816

  11. Vitamin D receptor gene polymorphisms and breast cancer risk among postmenopausal Egyptian women.

    PubMed

    Abd-Elsalam, Eman Abd-Elkader; Ismaeil, Nadia A; Abd-Alsalam, Hoda Sibai

    2015-08-01

    Many studies reported that vitamin D can protect against various types of cancers. The mechanism of vitamin D action is mediated by the vitamin D receptor (VDR). VDR may have anti-stress function because it has been identified as p53 direct target gene. This research was designed to investigate the role of VDR polymorphisms BsmI (rs 1544410), ApaI (rs 7975232), TaqI (rs 731236), and FokI (rs 10735810) in pathogenesis of breast cancer using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The study included 130 postmenopausal breast cancer cases aged 49 to 65 years and 100 controls aged 50 to 72 years. A significantly increased risk of breast cancer among carriers of BsmI bb genotype was observed (OR = 2.5 (1.1-5.6), P = 0.025). Also, a significantly increased risk of breast cancer was detected among women carrying ApaI aa genotype (OR = 2.2 (1.02-4.5), P = 0.04), while no significant associations were observed between breast cancer risk and genotypes and allele frequencies of FokI and TaqI polymorphisms (P > 0.05). Our study showed that VDR gene polymorphisms (BsmI and ApaI) may contribute to breast cancer risk among postmenopausal women. PMID:25804799

  12. Influence of Angiotensin I-Converting Enzyme Gene Polymorphism on Hepatocellular Carcinoma Risk in China

    PubMed Central

    Yuan, Fang; Zhang, Lu-Shun; Li, Hong-Yu; Liao, Miao

    2013-01-01

    Growing evidence suggests that the angiotensin-converting enzyme (ACE) and endothelial nitric oxide synthase (eNOS) genes are associated with risk in a wide range of cancers. The objective of this study was to examine whether two DNA polymorphisms at the ACE insertion/deletion (I/D) and the variable number of tandem repeats in NOS intron 4 (4a/4b) were linked to the risk of developing hepatocellular carcinoma (HCC) in a Chinese population. The polymorphisms at ACE I/D and eNOS 4a/4b were genotyped in 293 HCC patients and 384 healthy control subjects using polymerase chain reaction. The frequencies of the D allele (p=0.003, OR=0.72, 95% CI=0.58–0.90) in the ACE gene of HCC patients were significantly different from the healthy controls, and a significantly decreased HCC risk was associated with the DD genotype in both the recessive (p<0.001, OR=0.19, 95% CI=0.11–0.34) and codominant models (p<0.001, OR=0.26, 95% CI=0.14–0.48). This study provided evidence that the ACE I/D polymorphism is associated with HCC, indicating that the ACE I/D polymorphism contributes to HCC progression in the Chinese population. PMID:23570557

  13. CCL2 gene polymorphism is associated with post-transplant diabetes mellitus.

    PubMed

    Dabrowska-Zamojcin, Ewa; Romanowski, Maciej; Dziedziejko, Violetta; Maciejewska-Karlowska, Agnieszka; Sawczuk, Marek; Safranow, Krzysztof; Domanski, Leszek; Pawlik, Andrzej

    2016-03-01

    Post-transplant diabetes mellitus (PTDM) is a common complication after solid organ transplantation, especially in recipients treated with calcineurin inhibitors. Previous studies suggest that chronic inflammation and chemokines play an important role in the pathogenesis of diabetes. Single-nucleotide polymorphisms (SNPs) can increase or decrease transcriptional activity and can change the production of chemokines. The aim of this study was to examine the association between CCL2 and CCL5 gene polymorphisms and the development of post-transplant diabetes mellitus. The study included 315 patients who received kidney transplants and were treated with calcineurin inhibitors. Patients were divided into two subgroups: with PTDM (n=43) and without PTDM (n=272). An additive model of univariate Cox regression analysis showed that the hazard of PTDM development was significantly positively associated with the number of CCL2 rs1024611 G alleles (HR 1.65; 95%CI 1.08-2.53; p=0.021). Multivariate Cox regression analysis, taking into the account the recipient's sex, age and BMI, as well as the number of G alleles of the CCL2 rs1024611 polymorphism, revealed that this polymorphism is an independent risk factor for post-transplant diabetes. The results of our study suggest an association between the CCL2 gene rs1024611 G allele and PTDM in patients treated with tacrolimus or cyclosporine. PMID:26802601

  14. The Impact of Gene Polymorphisms on the Success of Anticholinergic Treatment in Children with Overactive Bladder

    PubMed Central

    Gurocak, Serhat; Konac, Ece; Ure, Iyimser; Senol, Cem; Onen, Ilke Hacer; Sozen, Sinan; Menevse, Adnan

    2015-01-01

    Aim. To determine the impact of gene polymorphisms on detrusor contraction-relaxation harmony in children with lower urinary tract symptoms (LUTS). Materials and Methods. Toilet trained children older than 5 years of age with LUTS and normal neurological examination underwent videourodynamic study. The control group was composed of age matched children with no voiding complaints. The study group who filled out the voiding dysfunction symptom score before and after the treatment received standard oxybutynin treatment and was reevaluated 1 year after treatment. Genomic DNA was isolated from all patients and subjected to PCR for amplification. Genotyping of ARGHEF10, ROCK2, ADRB3, and CYP3A4 was carried out with Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) method. Results. 34 (45%) and 42 (55%) patients were enrolled in the study and control group, respectively. ARGEF10 GG, ADRB3 TC, and CYP3A4 AG genotype patients displayed insignificant difference between pre- and posttreatment voiding dysfunction symptom score and bladder volumes. Conclusions. The polymorphism of genes in the cholinergic pathway did not significantly differ clinical parameters. On the other hand, polymorphic patients in the adrenergic pathway seemed to suffer from clinical disappointment. For this reason, we think that the neglected adrenergic pathway could be a new therapeutic target for the treatment of anticholinergic resistant LUTS in children. PMID:26166934

  15. Gene-disease association with human IFNL locus polymorphisms extends beyond hepatitis C virus infections.

    PubMed

    Chinnaswamy, S

    2016-07-01

    Interferon (IFN) lambda (IFN-λ or type III IFN) gene polymorphisms were discovered in the year 2009 to have a strong association with spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection in human hosts. This landmark discovery also brought renewed interest in type III IFN biology. After more than half a decade since this discovery, we now have reports that show that genetic association of IFNL gene polymorphisms in humans is not limited only to HCV infections but extends beyond, to include varied diseases such as non-alcoholic fatty liver disease, allergy and several other viral diseases including that caused by the human immunodeficiency virus. Notably, all these conditions have strong involvement of host innate immune responses. After the discovery of a deletion polymorphism that leads to the expression of a functional IFN-λ4 as the prime 'functional' variant, the relevance of other polymorphisms regulating the expression of IFN-λ3 is in doubt. Herein, I seek to critically address these issues and review the current literature to provide a framework to help further understanding of IFN-λ biology. PMID:27278127

  16. Impact of ESR1 Gene Polymorphisms on Migraine Susceptibility: A Meta-Analysis.

    PubMed

    Li, Li; Liu, Ruozhuo; Dong, Zhao; Wang, Xiaolin; Yu, Shengyuan

    2015-09-01

    An increasing number of studies have explored genetic associations between the functionally important polymorphisms in estrogen receptor 1 (ESR1) gene and migraine susceptibility. The previously reported associations have nevertheless been inconsistent.The present work incorporating the published data derived from 8 publications was performed to assess the impact of these polymorphisms on incident migraine. Strength of the genetic risk was estimated by means of an odds ratio along with the 95% confidence interval (OR and 95% CI).From the results, we found individuals who harbored the 325-GG genotype, compared with those harboring the CC genotype or CG and CC combined genotypes, had almost 50% greater risk of migraine. The same genetic models showed notable associations in subgroups of Caucasians and migraine with aura (MA). For 594G>A, a moderately increased risk of migraine was seen under AG versus GG. The AA + AG versus GG model, however, showed a borderline association with migraine. Subgroup analyses according to ethnicity and subtype of migraine provided statistical evidence of significantly increased risk of migraine in Caucasians and of a marginal association with MA, respectively. Both 325C>G and 594G>A polymorphisms showed no major effects either in males or in females.Based on the statistical data, we conclude some of the ESR1 gene polymorphisms may have major contributions to the pathogenesis of migraine in Caucasian populations. PMID:26334887

  17. Associations between gene polymorphisms of the apelin-APJ system and the risk of hypertension.

    PubMed

    Huang, Feng; Zhu, Pengli; Huang, Qiuxia; Yuan, Yin; Lin, Fan; Li, Qiaowei

    2016-08-01

    The aim of this study was to assess the associations between single nucleotide polymorphisms (SNPs) of the apelin and APJ (apelin receptor) genes and the risk of hypertension in people living in the south-east coastal area of China. A cross-sectional study involving 1031 participants was performed. Genotypes of the apelin (rs3115757, rs56204867 and rs3761581) and APJ (rs7119375 and rs9943582) genes were determined by the TaqMan® MGB probe method. For male patients, the frequencies of mutant alleles in the three apelin gene SNPs were significantly different between the hypertension and control groups (all p < 0.05), while no significant difference was obtained for frequencies of mutant alleles in the two APJ gene SNPs (p > 0.05). For females, the frequencies of mutant alleles in all five SNPs were not significantly different between the hypertension and control groups (all p > 0.05). After adjusting for several factors, the risk of developing hypertension increased significantly in patients, regardless of gender, carrying rs3115757-C, rs56204867-C or rs3761581-A allele (all p < 0.05). The optimal gene-gene interaction model for both males and females with regard to hypertension was apelin rs3761581-apelin rs3115757-APJ rs7119375. In conclusion, gene polymorphisms of the apelin-APJ system are associated with susceptibility to hypertension. PMID:27338090

  18. Molecular cloning, polymorphisms, and expression analysis of the RERG gene in indigenous Chinese goats.

    PubMed

    Sui, M X; Wang, H H; Wang, Z W

    2015-01-01

    The current study aimed to investigate the coding sequence, polymorphisms, and expression of the RERG gene in indigenous Chinese goats. cDNA of RERG, obtained through reverse transcription PCR was analyzed using bioinformatic techniques. Polymorphisms in the exon regions of the RERG gene were identified and their associations with growth traits in three varieties of indigenous Chinese goats were investigated. Expression of the RERG gene in three goat breeds of the same age was detected using real-time quantitative PCR. The results revealed that the cDNA of RERG, which contained a complete open reading frame of 20-620 bp, was 629 bp in length. The associated accession numbers in GenBank are JN672576, JQ917222, and JN580309 for the QianBei Ma goat, the GuiZhou white goat, and the GuiZhou black goat, respectively. Four consistent SNP sites were found in the exon regions of the RERG gene for the three goat breeds. mRNA expression of the RERG gene differed between different tissues in adult goats of same age. The highest expression was observed in lung and spleen tissues, while the lowest expression was recorded in thymus gland tissue. In addition, the expression of the RERG gene in the muscle of Guizhou white goat, GuiZhou black goat, and QianBei Ma goat decreased sequentially. Our results lay the foundations for further investigation into the role of the RERG gene in goat growth traits. PMID:26634455

  19. Renin–angiotensin system gene polymorphisms and endometrial cancer

    PubMed Central

    Delforce, Sarah J; Wang, Yu; Ashton, Katie A; Proietto, Anthony; Otton, Geoffrey; Blackwell, C Caroline; Scott, Rodney J; Lumbers, Eugenie R

    2016-01-01

    Endometrial cancer (EC) is the most common gynaecological malignancy and its incidence is increasing. Dysregulation of the endometrial renin–angiotensin system (RAS) could predispose to EC; therefore, we studied the prevalence of RAS single nucleotide polymorphisms (SNPs) in Australian women with EC. SNPs assessed were AGT M235T (rs699); AGTR1 A1166C (rs5186); ACE A240T and T93C (rs4291, rs4292) and ATP6AP2 (rs2968915). They were identified using TaqMan SNP Genotyping Assays. The C allele of the AGTR1 SNP (rs5186) was more prevalent in women with EC (odds ratio (OR) 1.7, 95% confidence interval (CI) (1.2–2.3), P=0.002). The CC genotype of this SNP is associated with upregulation of the angiotensin II type 1 receptor (AGTR1). The G allele of AGT rs699, which is associated with higher angiotensinogen (AGT) levels, was less prevalent in women with EC (OR 0.54, 95% CI (0.39–0.74), P<0.001) compared with controls. AGT and AGT formed by removal of angiotensin I (des(Ang I)AGT) are both anti-angiogenic. In women with EC who had had hormone replacement therapy (HRT), the prevalence of the AGTR1 SNP (rs5186) and the ACE SNPs (rs4291 and rs4292) was greater than in women who had no record of HRT; SNP rs4291 is associated with increased plasma ACE activity. These data suggest there is an interaction between genotype, oestrogen replacement therapy and EC. In conclusion, the prevalence of two SNPs that enhance RAS activity was different in women with EC compared with healthy controls. These genetic factors may interact with obesity and hyperoestrogenism, predisposing ageing, obese women to EC. PMID:27068935

  20. Renin-angiotensin system gene polymorphisms and endometrial cancer.

    PubMed

    Pringle, Kirsty G; Delforce, Sarah J; Wang, Yu; Ashton, Katie A; Proietto, Anthony; Otton, Geoffrey; Blackwell, C Caroline; Scott, Rodney J; Lumbers, Eugenie R

    2016-05-01

    Endometrial cancer (EC) is the most common gynaecological malignancy and its incidence is increasing. Dysregulation of the endometrial renin-angiotensin system (RAS) could predispose to EC; therefore, we studied the prevalence of RAS single nucleotide polymorphisms (SNPs) in Australian women with EC. SNPs assessed were AGT M235T (rs699); AGTR1 A1166C (rs5186); ACE A240T and T93C (rs4291, rs4292) and ATP6AP2 (rs2968915). They were identified using TaqMan SNP Genotyping Assays. The C allele of the AGTR1 SNP (rs5186) was more prevalent in women with EC (odds ratio (OR) 1.7, 95% confidence interval (CI) (1.2-2.3), P=0.002). The CC genotype of this SNP is associated with upregulation of the angiotensin II type 1 receptor (AGTR1). The G allele of AGT rs699, which is associated with higher angiotensinogen (AGT) levels, was less prevalent in women with EC (OR 0.54, 95% CI (0.39-0.74), P<0.001) compared with controls. AGT and AGT formed by removal of angiotensin I (des(Ang I)AGT) are both anti-angiogenic. In women with EC who had had hormone replacement therapy (HRT), the prevalence of the AGTR1 SNP (rs5186) and the ACE SNPs (rs4291 and rs4292) was greater than in women who had no record of HRT; SNP rs4291 is associated with increased plasma ACE activity. These data suggest there is an interaction between genotype, oestrogen replacement therapy and EC. In conclusion, the prevalence of two SNPs that enhance RAS activity was different in women with EC compared with healthy controls. These genetic factors may interact with obesity and hyperoestrogenism, predisposing ageing, obese women to EC. PMID:27068935

  1. Interleukin-10 -1082 G/A gene polymorphisms in Egyptian children with CAP

    PubMed Central

    Azab, Seham F.; Abdalhady, Mohamed A.; Elsaadany, Hosam F.; Elkomi, Mohamed A.; Elhindawy, Eman M.; Sarhan, Dina T.; Salam, Mohamed M.A.; Allah, Mayy A.N.; Emam, Ahmed A.; Noah, Maha A.; Abdelsalam, Nasser I.; Abdellatif, Sawsan H.; Rass, Anwar A.; Ismail, Sanaa M.; Gheith, Tarek; Aziz, Khalid A.; Hamed, Mohammed E.; Abdelrahman, Hind M.; Ahmed, Ahmed R.; Nabil, Rehab M.; Abdulmaksoud, Rehab S.; Yousef, Hala Y.

    2016-01-01

    Abstract Community-acquired pneumonia (CAP) is one of the leading causes of death worldwide. Cytokines are involved in the pathogenesis of CAP. To date, only a few studies concerned the association of interleukin-10 (IL-10) gene polymorphisms with CAP. In this study, we aimed to investigate whether the -1082(G/A) polymorphism in the promoter region of the IL-10 gene is involved in susceptibility to and the outcome of CAP, and we also measured the serum level of IL-10 to assess its relation to such polymorphism. This was a case–control study included 100 patients with CAP, and matched with age, gender, and ethnicity of 100 healthy control children. IL-10 -1082(G/A) gene polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism, while the serum IL-10 levels were measured by ELISA method. Compared to the controls subjects, the frequencies of the IL-10 -1082 AA genotype and A allele were observed to be overrepresented in patients with CAP (51%; odds ratio [OR] = 2.8; 95% confidence interval [CI]: 1.5–5.3 for the AA genotype; P < 0.01) and (70%; OR: 1.95; 95% CI: 1.27–3.00 for the A allele; P < 0.01, respectively). We found that patients with the GG genotype had significantly higher serum IL-10 levels (46.7 ± 9.5 pg/mL) compared to those with AG genotype (21.8 ± 4.5 pg/mL) and AA genotype (11.5 ± 3.3 pg/mL); P < 0.01, respectively. Our data revealed a significant positive association between the -1082 GG genotype and susceptibility to severe sepsis, acute respiratory failure, and hospital mortality (OR: 3.8; 95% CI: 1.3–11.2; P < 0.01). We demonstrate for the first time, to the best of our knowledge, that IL-10 -1082 (G/A) gene polymorphism may contribute to susceptibility to CAP in Egyptian children. Moreover, we observed that the presence of a G allele or GG genotype at the -1082 position of the promoter region of the IL-10 gene constitute risk factors for developing severe sepsis

  2. Association between Apolipoprotein C-III Gene Polymorphisms and Coronary Heart Disease: A Meta-analysis

    PubMed Central

    Zhang, Jing-Zhan; Xie, Xiang; Ma, Yi-Tong; Zheng, Ying-Ying; Yang, Yi-Ning; Li, Xiao-Mei; Fu, Zhen-Yan; Dai, Chuan-Fang; Zhang, Ming-Ming; Yin, Guo-Ting; Liu, Fen; Chen, Bang-Dang; Gai, Min-Tao

    2016-01-01

    Polymorphisms in the apolipoprotein C-III (APOC3) gene have been reported to be associated with coronary heart disease (CHD), but the data so far have been conflicting. To derive a more precise estimation of these associations, we performed a meta-analysis to investigate the three main polymorphisms (SstI, T-455C, C-482T) of APOC3 in all published studies. Databases including PubMed, Web of Science, Wanfang, SinoMed and CNKI were systematically searched. The association was assessed using odds ratios (ORs) with 95% confidence intervals (CIs). The statistical analysis was performed using Review Manager 5.3.3 and Stata 12.0. A total of 31 studies have been identified. The pooled odds ratio (OR) for the association between the APOC3 gene polymorphisms and CHD and its corresponding 95% confidence interval (95% CI) were evaluated by random or fixed effect models. A statistical association between APOC3 SstI polymorphism and CHD susceptibility was observed under an allelic contrast model (P= 0.003, OR = 1.14, 95% CI = 1.05-1.24), dominant genetic model (P= 0.01, OR = 1.14, 95% CI = 1.03-1.26), and recessive genetic model (P= 0.02, OR = 1.35, 95% CI = 1.06-1.71), respectively. A significant association between the APOC3 T-455C polymorphism and CHD was also detected under an allelic contrast (P < 0.0001, OR = 1.19, 95% CI = 1.10-1.29), dominant genetic model (P= 0.0003, OR = 1.24, 95% CI = 1.11-1.39) and recessive genetic model (P= 0.04, OR = 1.30, 95% CI = 1.01-1.67). No significant association between the APOC3 C-482T polymorphism and CHD was found under an allelic model (P= 0.94, OR = 1.00, 95% CI = 0.93-1.08), dominant genetic model (P= 0.20, OR = 1.07, 95% CI = 0.97-1.18) or recessive genetic model (P= 0.13, OR = 0.90, 95% CI = 0.79-1.03). This meta-analysis revealed that the APOC3 SstI and T-455C polymorphisms significantly increase CHD susceptibility. No significant association was observed between the APOC3 C-482T polymorphism and CHD susceptibility. PMID:26816662

  3. Cytochrome P450 CYP2D6 gene polymorphism and lung cancer susceptibility in Caucasians.

    PubMed

    Legrand-Andréoletti, M; Stücker, I; Marez, D; Galais, P; Cosme, J; Sabbagh, N; Spire, C; Cenée, S; Lafitte, J J; Beaune, P; Broly, F

    1998-02-01

    Many studies have been performed in an attempt to establish a link between the polymorphism of the cytochrome P450 CYP2D6 gene and the incidence of lung cancer. Nevertheless, whether or not this genetic polymorphism has a role in the development of the disease remains unclear. Recently, new advances in our knowledge of the CYP2D6 gene and its locus (CYP2D) have been achieved. In particular, CYP2D6 was found to be highly polymorphic and multiple novel mutations and allelic variants of the gene have been identified. In addition, a number of CYP2D rearrangements, including those with amplification of the gene, have been demonstrated. Taking this new information into account, we have reconsidered the potential influence of CYP2D6 polymorphism in lung cancer susceptibility by performing a comparative analysis of the overall mutational spectrum of CYP2D6 and of the rearrangements of CYP2D in 249 patients with lung cancer and in 265 control individuals matched on age, sex, hospital and residence area. For this purpose, a strategy based on SSCP analysis of the entire coding sequence of CYP2D6 and on RFLP analysis of the gene locus was carried out in DNA samples from each individual. Forty mutations occurring in various combinations on 42 alleles of the gene and 82 different genotypes were identified. No significant difference in the distribution of the mutations, alleles or genotypes was observed between the two groups, except a particular genotype (CYP2D6*1A/*2), which was more common in the sub-group of moderate smokers (< 30 pack-years) suffering from small cell carcinoma (Odds Ratio (OR) 3.6, 95% CI 1.1-11.9). When the phenotype was predicted according to genotype, only a trend toward a higher frequency of ultrarapid metabolizers in patients was obtained. In spite of a complete analysis of the CYP2D6 gene and its locus, this case-control study provides elements against an influence of the CYP2D6 polymorphism on lung cancer susceptibility. PMID:9511176

  4. POLYMORPHISM OF THE PROLACTIN GENE AND ITS EFFECT ON FIBER TRAITS IN GOAT.

    PubMed

    Shamsalddini, S; Mohammadabadi, M R; Esmailizadeh, A K

    2016-04-01

    The prolactin gene (PRL) is a potential candidate gene for the goat cashmere traits in marker-assisted selection. Thus, the aim of this study was to detect PRL gene polymorphism and its association with fiber traits in 200 Raini cashmere goats native to the south-east of Iran. A 196-bp fragment encoding exon 5 within the goat PRL gene was amplified using PCR specific primers. The amplification products were subjected to the single stranded conformation polymorphism (SSCP) analysis. Three different SSCP banding patterns (CC, AC and AA) were observed in exon 5 of the caprine PRL gene. The pattern frequencies for CC, AC and AA were 0.39, 0.38 and 0.23 and frequencies of the A and C alleles were 0.42 and 0.58, respectively. The genotypic distributions did not deviate from the Hardy-Weinberg equilibrium (P> 0.05). The number of observed alleles, number of effective alleles, expected heterozygosity, observed heterozygosity, mean of heterozygosity, expected homozygosity, observed homozygosity, Nei's index and Shanon's index were 2.0, 1.9, 0.48, 0.38, 0.48, 0.51, 0.61, 0.48 and 0.68, respectively. Results of association between genotypes and fiber traits indicated that the CC genotype had the highest fiber length compared with the AA and AC genotypes (P < 0.05) while there was no significant association between the PRL gene genotypes and fiber diameter. These results imply that the PRL gene polymorphism can be used as a molecular marker to improve fiber production without a negative effect on fiber diameter. PMID:27529980

  5. Genetic analysis of polymorphisms in biologically relevant candidate genes in patients with abdominal aortic aneurysms

    PubMed Central

    Ogata, Toru; Shibamura, Hidenori; Tromp, Gerard; Sinha, Moumita; Goddard, Katrina A. B.; Sakalihasan, Natzi; Limet, Raymond; MacKean, Gerald L.; Arthur, Claudette; Sueda, Taijiro; Land, Susan; Kuivaniemi, Helena

    2005-01-01

    Background Abdominal aortic aneurysms (AAAs) are characterized by histologic signs of chronic inflammation, destructive remodeling of extracellular matrix, and depletion of vascular smooth muscle cells. We investigated the process of extracellular matrix remodeling by performing a genetic association study with polymorphisms in the genes for matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and structural extracellular matrix molecules in AAA. Our hypothesis was that genetic variations in one or more of these genes contribute to greater or lesser activity of these gene products, and thereby contribute to susceptibility for developing AAAs. Methods DNA samples from 812 unrelated white subject (AAA, n = 387; controls, n = 425) were genotyped for 14 polymorphisms in 13 different candidate genes: MMP1(nt−1607), MMP2(nt−955), MMP3(nt−1612), MMP9(nt−1562), MMP10(nt+180), MMP12(nt−82), MMP13(nt−77), TIMP1(nt+434), TIMP1(rs2070584), TIMP2(rs2009196), TIMP3(nt−1296), TGFB1(nt−509), ELN(nt+422), and COL3A1(nt+581). Odds ratios and P values adjusted for gender and country of origin using logistic regression and stratified by family history of AAA were calculated to test for association between genotype and disease status. Haplotype analysis was carried out for the two TIMP1 polymorphisms in male subjects. Results Analyses with one polymorphism per test without interactions showed an association with the two TIMP1 gene polymorphisms (nt+434, P = .0047; rs2070584, P = .015) in male subjects without a family history of AAA. The association remained significant when analyzing TIMP1 haplotypes (χ2 P = .014 and empirical P = .009). In addition, we found a significant interaction between the polymorphism and gender for MMP10 (P = .037) in cases without a family history of AAA, as well as between the polymorphism and country of origin for ELN (P = .0169) and TIMP3 (P = .0023) in cases with a family history of AAA. Conclusions These

  6. No Association between Oxytocin Receptor (OXTR) Gene Polymorphisms and Experimentally Elicited Social Preferences

    PubMed Central

    Apicella, Coren L.; Cesarini, David; Johannesson, Magnus; Dawes, Christopher T.; Lichtenstein, Paul; Wallace, Björn; Beauchamp, Jonathan; Westberg, Lars

    2010-01-01

    Background Oxytocin (OXT) has been implicated in a suite of complex social behaviors including observed choices in economic laboratory experiments. However, actual studies of associations between oxytocin receptor (OXTR) gene variants and experimentally elicited social preferences are rare. Methodology/Principal Findings We test hypotheses of associations between social preferences, as measured by behavior in two economic games, and 9 single nucleotide polymorphisms (SNPs) of the OXTR gene in a sample of Swedish twins (n = 684). Two standard economic games, the dictator game and the trust game, both involving real monetary consequences, were used to elicit such preferences. After correction for multiple hypothesis testing, we found no significant associations between any of the 9 single nucleotide polymorphisms (SNPs) and behavior in either of the games. Conclusion We were unable to replicate the most significant association reported in previous research between the amount donated in a dictator game and an OXTR genetic variant. PMID:20585395

  7. Dopamine transporter gene polymorphism and psychiatric symptoms seen in schizophrenic patients at their first episode

    SciTech Connect

    Inada, Toshiya; Sugita, Tetsuyoshi; Dobashi, Izumi

    1996-07-26

    To investigate the possible role of the dopamine transporter (DAT) gene in determining the phenotype in human subjects, allele frequencies for the 40-bp variable number of tandem repeats (VNTR) polymorphism at this site were compared between 117 Japanese normal controls and 118 schizophrenic patients, including six subgroups: early-onset, those with a family history, and those suffering from one of the following psychiatric symptoms at their first episode: delusion and hallucination; disorganization; bizarre behavior; and negative symptoms. No significant differences were observed between the group as a whole or any subgroup of schizophrenic patients and controls. The results indicate that VNTR polymorphism in the DAT gene is unlikely to be a major contributor to any of the psychiatric parameters examined in the present population of schizophrenic subjects. 12 refs., 1 fig., 2 tabs.

  8. Renal hemodynamic changes induced by captopril and angiotensin-converting enzyme gene polymorphism.

    PubMed

    Mizuiri, S; Hemmi, H; Inoue, A; Takano, M; Kadomatsu, S; Tanimoto, H; Tanegashima, M; Hayashi, I; Fushimi, T; Hasegawa, A

    1997-01-01

    We studied the relationship between renal hemodynamic changes induced by a single acute administration of captopril (50 mg p.o.) and angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in 27 healthy human volunteers, 7 with DD genotype, 10 with ID, and 10 with II genotype. The increase in effective renal plasma flow (p < 0.02) and the fall in renal vascular resistance (p < 0.01) in response to captopril were significantly less in subjects with the DD genotype than in subjects with the other genotypes. These data suggest that intrarenal ACE inhibition by captopril differs according to ACE gene ID polymorphism in healthy humans. PMID:9069453

  9. Correlation between C677T MTHFR gene polymorphism, plasma homocysteine levels and the incidence of CAD.

    PubMed

    Nakai, K; Itoh, C; Nakai, K; Habano, W; Gurwitz, D

    2001-01-01

    The lesions of coronary atherosclerosis represent the result of a complex, multicellular, inflammatory-healing response in the coronary arterial wall. In vivo and in vitro cellular and molecular studies have suggested a role for tissue homocysteine in endothelial cell injury and adverse extra-cellular matrix remodeling. Gene polymorphisms in relation with numerous risk factors might increase the incidence of coronary artery disease (CAD). In this review we have focused on the correlations between plasma homocysteine levels, the incidence of cardiovascular disease and the cytosine-to-thymidine substitution at nucleotide 677 (C677T) of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, coding for a key enzyme in methionine-homocysteine metabolism. The role of the C677T MTHFR gene polymorphism in the causation of CAD is controversial. We reviewed 12 recent case-control studies comprising 5370 genotyped patients with CAD and 4961 genotyped participants without CAD. There was no significant difference between those with and without CAD in the frequency of the C677T polymorphism (34.9 vs 33.6%). The frequency of homozygous C677T polymorphism in these groups was 10.9 versus 12.8%, respectively, although there were some ethnic differences in the C677T MTHFR polymorphism. In the analysis of the 12 studies, the odds ratio of CAD associated with the TT genotype (homozygous C677T polymorphism) was 1.18. Only slightly higher plasma homocysteine levels were observed in participants with the val/val (TT) genotype (14.4+/-2.9 micro mol/L in TT genotype vs 11.1+/-1.9 and 11.9+/-2 micro mol/L in CC and CT genotype, respectively). In addition, the relation between homocysteine increase after methionine loading and MTHFR genotypes is also controversial. However, hyperhomocysteinemia because of the C677T MTHFR allele may be corrected with oral folic acid therapy. Further investigations on the relationships between MTHFR genotypes and the incidence of CAD should be based on

  10. Genetic mapping of the beta 1 GABA receptor gene to human chromosome 4, using a tetranucleotide repeat polymorphism.

    PubMed Central

    Dean, M; Lucas-Derse, S; Bolos, A; O'Brien, S J; Kirkness, E F; Fraser, C M; Goldman, D

    1991-01-01

    As more coding loci for functional human genes are described, there is a growing need to identify DNA polymorphisms in specific genes. By examining DNA sequences within the introns of the beta 1 subunit of the gamma-aminobutyric acid receptor gene, GABARB1, we found a tetranucleotide repeat sequence (GATA). Amplification of this region by using PCR revealed seven alleles and a high degree of polymorphism (PIC = .75) in human populations. DNAs from the CEPH families were typed for the GABARB1 intron polymorphism and were analyzed with respect to 20 linked markers on chromosome 4. The results permit placement of GABARB1 on the linkage map of chromosome 4, between D4S104 and ALB. These results affirm that sequence analysis of noncoding segments included within or adjacent to functional genes has value as a strategy to detect highly informative polymorphisms. Images Figure 2 PMID:1652891

  11. FCRL3 Gene Polymorphisms Confer Autoimmunity Risk for Allergic Rhinitis in a Chinese Han Population

    PubMed Central

    Gu, Zheng; Hong, Su-Ling; Ke, Xia; Shen, Yang; Wang, Xiao-Qiang; Hu, Di; Hu, Guo-Hua; Kang, Hou-Yong

    2015-01-01

    Background Heredity and environmental exposures may contribute to a predisposition to allergic rhinitis (AR). Autoimmunity may also involve into this pathologic process. FCRL3 (Fc receptor-like 3 gene), a novel immunoregulatory gene, has recently been reported to play a role in autoimmune diseases. Objective This study was performed to evaluate the potential association of FCRL3 polymorphisms with AR in a Chinese Han population. Methods Five single-nucleotide polymorphisms of FCRL3, rs945635, rs3761959, rs7522061, rs10489678 and rs7528684 were genotyped in 540 AR patients and 600 healthy controls using a PCR-restriction fragment length polymorphism assay. Allele, genotype and haplotype frequencies were compared between patients and controls using the χ2 test. The online software platform SHEsis was used to analyze their haplotypes. Results This study identified three strong risk SNPs rs7528684, rs10489678, rs7522061 and one weak risk SNP rs945635 of FCRL3 in Chinese Han AR patients. For rs7528684, a significantly increased prevalence of the AA genotype and A allele in AR patients was recorded. The frequency of the GG genotype and G allele of rs10489678 was markedly higher in AR patients than those in controls. For rs7522061, a higher frequency of the TT genotype, and a lower frequency of the CT genotype were found in AR patients. Concerning rs945635, a lower frequency of the CC genotype, and a higher frequency of G allele were observed in AR patients. According to the analysis of the three strong positive SNPs, the haplotype of AGT increased significantly in AR cases (AR = 38.8%, Controls = 24.3%, P = 8.29×10-14, OR [95% CI] 1.978 [1.652~2.368]). Conclusions This study found a significant association between the SNPs in FCRL3 gene and AR in Chinese Han patients. The results suggest these gene polymorphisms might be the autoimmunity risk for AR. PMID:25594855

  12. Association of UBASH3A gene polymorphisms and systemic lupus erythematosus in a Chinese population.

    PubMed

    Liu, Jie; Liu, Juan; Ni, Jing; Leng, Rui Xue; Pan, Hai Feng; Ye, Dong Qing

    2015-07-01

    Recent evidence has demonstrated that UBASH3A gene was associated with multiple autoimmune diseases. The aim of this study was to explore the association between UBASH3A gene single-nucleotide polymorphisms (SNPs) and systemic lupus erythematosus (SLE) in a Chinese Han population. Four UBASH3A polymorphisms (rs11203203, rs3788013, rs2277798, and rs1893592) were genotyped using the Fluidigm 192.24 Dynamic Array™ Integrated Fluidic Circuit (IFC). Data were analyzed by SPSS 11.5 software. A total of 792 SLE patients and 777 healthy controls were included in this study. The CC genotype and C allele of rs3788013 polymorphism were more frequent in the patient group than in controls (OR=1.583, 95% CI=1.095-2.287; OR=1.258, 95% CI=1.083-1.461, respectively). We also found a statistical significance under the recessive model (OR=1.298, 95% CI=1.049-1.607, p=0.017). The frequency of variant genotype AC of rs3788013 was associated with the phenotype of vasculitis (p=0.012). A statistically significant association was observed between UBASH3A rs1893592 C allele and skin rash, oral ulcer and arthritis (p<0.05). Moreover, we found that the genotype distribution of rs2277798 was significantly associated with hematuria in the SLE patients (p=0.003). However, UBASH3A rs11203203, rs2277798, and rs1893592 polymorphisms were not associated with the risk of SLE (p>0.05). The findings suggest that UBASH3A gene might contribute to SLE susceptibility and influence the clinical phenotype of the disease. Further studies are necessary to elucidate the exact role of UBASH3A gene in the pathogenesis of SLE. PMID:25843625

  13. [Polymorphism of the kappa-casein gene in populations of the subfamily Bovinae].

    PubMed

    Sulimova, G E; Badagueva, Iu N; Udina, I G

    1996-11-01

    Polymorphism of the 5'-untranslated region and exon 4 of kappa-casein (kappa-casein) gene was studied in Yakutian and Black Pied cattle, yak, European bison, and buffalo by means of a polymerase chain reaction and subsequent restriction fragment length polymorphism analysis (PCR-RFLP). In the species studied, restriction polymorphism by the endonucleases AluI and Bg/II in the 5'-untranslated region of the gene is absent. Four restriction endonucleases testing nucleotide substitutions in 136 codon (TaqI), 148 codon (HinfI and HindIII), and 167 and 168 codons (PstI) were used to study polymorphism of exon 4. The use of several restriction endonucleases allowed three alleles of kappa-casein (kappa-CnA, kappa-CnB, kappa-CnF) to be typed and new allele variants in yak, European bison, and buffalo to be revealed. Nucleotide sequences of the fragments of exon 4 studied were determined for two new alleles of the gene: kappa-CnG in yak and European bison and kappa-CnH in buffalo. Nucleotide substitutions determining new alleles were localized. In kappa-CnG, 148 and 168 codons coincide with the corresponding codons of kappa-CnB, and 136 and 167 codons correspond to kappa-CnA. Stop codons of kappa-CnG in yak are different from stop codons of other alleles of the gene: TGA, instead of TAA. The nucleotide sequence of exon 4 of kappa-CnH differs from bovine kappa-CnA by 15 nucleotide substitutions, causing 10 amino acid changes in the protein sequence, which coincide with the corresponding known amino acid sequence of kappa-casein in buffalo. Interbreed and interspecies differences in the profile of allele frequencies of the species studied were revealed. Aspects connected with evolution of the alleles of kappa-casein are discussed. PMID:9119217

  14. Single nucleotide polymorphisms in G protein signaling pathway genes in preeclampsia.

    PubMed

    Kvehaugen, Anne Stine; Melien, Oyvind; Holmen, Oddgeir Lingaas; Laivuori, Hannele; Oian, Pål; Andersgaard, Alice Beathe; Dechend, Ralf; Staff, Anne Cathrine

    2013-03-01

    Preeclampsia is a pregnancy specific disorder and a risk factor for later cardiovascular disease. The cause and detailed pathophysiology remains unknown. G protein signaling is involved in a variety of physiological processes, including blood pressure regulation. We assessed whether distributions of 3 single nucleotide polymorphisms in genes coding for components of G protein signaling pathways that have been associated with hypertension differ between women with preeclampsia and normotensive pregnant women; the G protein β3 subunit gene (GNB3) C825T polymorphism (rs5443), the angiotensin II type 1 receptor gene (AGTR1) 3'UTR A1166C polymorphism (rs5186), and the regulator of G protein signaling 2 gene (RGS2) 3'UTR C1114G polymorphism (rs4606). Two separate Norwegian study populations were used; a large population based study and a smaller, but clinically well-described pregnancy biobank. A descriptive study of 43 women with eclampsia was additionally included. In the population-based study, an increased odds of preeclampsia (odds ratio, 1.21; [95% confidence interval, 1.05-1.40]; P=0.009) and recurrent preeclampsia (odds ratio, 1.43; [95% confidence interval, 1.06-1.92];, P=0.017) was found in women carrying the rs4606 CG or GG genotype. In early-onset preeclamptic patients with decidual spiral artery biopsies available (n=24), the rs4606 CG or GG genotype was more frequent in those with acute atherosis (resembling early stage of atherosclerosis) compared with those without: odds ratio, 15.0; (95% confidence interval, 2.02-111.2); P=0.004. No association was found between preeclampsia and the rs5443 or the rs5186. The genotype distribution in eclamptic women was not different from preeclamptic women. In conclusion, RGS2 rs4606 may affect the risk and progression of preeclampsia. PMID:23339167

  15. Leptin Receptor Gene Polymorphism may Affect Subclinical Atherosclerosis in Patients with Acromegaly

    PubMed Central

    Turgut, Sebahat; Topsakal, Senay; Ata, Melek Tunç; Herek, Duygu; Akın, Fulya; Özkan, Şeyma; Turgut, Günfer

    2016-01-01

    Background: Acromegaly is associated with increased morbidity and mortality related to cardiovascular diseases. Leptin (LEP) and Leptin Receptor (LEPR) gene polymorphisms can increase cardiovascular risks. The aim of this study was to investigate association between the frequencies of LEP and LEPR gene polymorphisms and subclinical atherosclerosis in acromegalic patients. Methods: Forty-four acromegalic patients and 30 controls were admitted to study. The polymorphisms were identified by using polymerase chain reaction from peripheral blood samples. The levels of systolic and diastolic blood pressure, BMI, fasting plasma glucose, fasting insulin, IGF-I, GH, IGFBP3, leptin, triglyceride, carotid Intima Media Thickness (cIMT) and HDL and LDL cholesterol concentrations were evaluated. Results: There was statistically significant difference between the LEPR genotypes of acromegalic patients (GG 11.4%, GA 52.3%, and AA 36.4%) and controls (GG 33.3%, GA 50%, and AA 16.7%) although their LEP genotype distribution was similar. In addition, the prevalence of the LEPR gene G and A alleles was significantly different between patients and controls. No significant difference was found among the G(-2548) A leptin genotypes of groups in terms of the clinical parameters. cIMT significantly increased homozygote LEPR GG genotype group compared to AA subjects in patients. But the other parameters were not different between LEPR genotypes groups of patients and controls. Conclusion: It can be said that the LEPR gene polymorphism may affect cIMT in patients. The reason is that LEPR GG genotype carriers may have more risk than other genotypes in the development of subclinical atherosclerosis in acromegaly. PMID:27563428

  16. Combined Adiponectin Deficiency and Resistance in Obese Patients: Can It Solve Part of the Puzzle in Nonalcoholic Steatohepatitis

    PubMed Central

    Salman, Ahmed; Hegazy, Mona; AbdElfadl, Soheir

    2015-01-01

    BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent cause of liver disease, nonalcoholic steatohepatitis (NASH) and fibrosis in obese patients identifies the risk group with increased incidence of liver-related deaths. AIM: To clarify the role of serum adiponectin and its receptor liver gene expression in the progression of liver damage in NAFLD. METHODS: Fifty four (54) obese patients with NAFLD preliminary diagnosed by liver ultra-sound were recruited. Full medical history, anthropometric measurement, biochemical studies, serum adiponectin level, liver biopsy for histological examination and NAS score to identify NASH patients, and assessment of adiponectin receptor gene expression by RT-PCR, were conducted for each patients. Fifteen ages matched average weight healthy adult had been chosen as a control for serum adiponectin level. RESULTS: According to NAS score, patients were divided into non- NASH (8 patients), and NASH (46 patients). Serum adiponectin level was significantly lower in NAFLD patients compared to normal participants (p < 0.004). Serum adiponectin level was lower in NASH patients (4.437 ± 2.569 ng/dl in NASH vs. 5.138 ± 2.841 ng/dl in non-NASH). Adiponectin receptor liver gene expression was lower in NASH patients (0.8459 ± 0.4671 vs. 1.0688 ± 0.3965 in non-NASH). CONCLUSION: Both adiponectin deficiency and resistance had a role in progression of simple liver steatosis to severe injury in obese patients. PMID:27275239

  17. Systematic assessment of the influence of complement gene polymorphisms on kidney transplant outcome.

    PubMed

    Ermini, Luca; Weale, Michael E; Brown, Katherine M; Mesa, Irene Rebollo; Howell, W Martin; Vaughan, Robert; Chowdhury, Paramit; Sacks, Steven H; Sheerin, Neil S

    2016-04-01

    The importance of the innate immune system, including complement, in causing transplant injury and augmenting adaptive immune responses is increasingly recognized. Therefore variability in graft outcome may in part be due to genetic polymorphism in genes encoding proteins of the immune system. This study assessed the relationship between single nucleotide polymorphisms (SNPs) in complement genes and outcome after transplantation. Analysis was performed on two patient cohorts of 650 and 520 transplant recipients. 505 tagged SNPs in 47 genes were typed in both donor and recipient. The relationships between SNPs and graft survival, serum creatinine, delayed graft function and acute rejection were analyzed. One recipient SNP in the gene encoding mannose binding lectin was associated with graft outcome after correction for analysis of multiple SNPs (p=6.41 × 10(-5)). When further correction was applied to account for analysis of the effect of SNPs in both donor and recipient this lost significance. Despite association p values of <0.001 no SNP was significantly associated with clinical phenotypes after Bonferroni correction. In conclusion, the variability seen in transplant outcome in this patient cohort cannot be explained by variation in complement genes. If causal genetic effects exist in these genes, they are too small to be detected by this study. PMID:26797657

  18. Association between vitamin D receptor gene Cdx2 polymorphism and breast cancer susceptibility.

    PubMed

    Zhou, Zhu-Chao; Wang, Jie; Cai, Zi-Hao; Zhang, Qun-hua; Cai, Zhen-Xin; Wu, Jian-Hua

    2013-12-01

    Vitamin D receptor (VDR) gene polymorphisms have been reported to influence susceptibility to breast cancer. However, published findings on the association between VDR Cdx2 polymorphism and breast cancer susceptibility are conflicting. To get a precise estimation of the association between VDR Cdx2 polymorphism and breast cancer susceptibility, we conducted a meta-analysis of four case-control studies with a total of 8,880 subjects (3,841 cases and 5,039 controls). The results showed that VDR Cdx2 polymorphism was not associated with risk of breast cancer (A versus G: OR = 0.96, 95% CI 0.84-1.09; AA versus GG: OR = 0.97, 95% CI 0.64-1.45; AA/GA versus GG: OR = 0.94, 95% CI 0.80-1.10; AA versus GG/GA: OR = 0.99, 95% CI 0.65-1.51). Subgroup analysis in Caucasians also showed that VDR Cdx2 polymorphism was not associated with risk of breast cancer in Caucasians. However, there was a significant association in Africans (A versus G: OR = 0.75, 95% CI 0.60-0.94; AA versus GG: OR = 0.53, 95% CI 0.29-0.99; AA/GA versus GG: OR = 0.75, 95% CI 0.57-0.97). Therefore, the association between VDR Cdx2 polymorphism and breast cancer susceptibility is only found in Africans. More studies are needed to further assess the association in Asians or Africans. PMID:23821301

  19. Thrombomodulin gene c.1418C>T polymorphism and risk of recurrent venous thromboembolism.

    PubMed

    Ahmad, Abrar; Sundquist, Kristina; Zöller, Bengt; Svensson, Peter J; Sundquist, Jan; Memon, Ashfaque A

    2016-07-01

    Thrombomodulin gene (THBD) is a critical cofactor in protein C anticoagulant system. THBD c.1418C>T polymorphism is reported to be associated with higher risk of primary venous thromboembolism (VTE) but its role in VTE recurrence is unknown. The aim of this study was to investigate the role of THBD polymorphism in VTE recurrence. THBD c.1418C>T polymorphism was genotyped by using Taqman polymerase chain reaction in a prospective population based study of 1465 consecutive objectively verified VTE patients. Uni- and multivariate Cox regression were performed for the risk assessment of VTE recurrence. Patients who had VTE before inclusion or had recurrence or died during anticoagulant treatment were excluded. Among the remaining (N = 1046) patients, 126 (12.05 %) had VTE recurrence during the follow up period (from 1998 to 2008). THBD polymorphism was not significantly associated with risk of VTE recurrence in the univariate [Hazard ratio (HR) 1.11, 95 % confidence interval (CI) 0.78-1.59, p = 0.55] as well as the multivariate analysis adjusted for age, sex and thrombophilia (HR 1.11, 95 % CI 0.78-1.59, p = 0.54). Similarly, in unprovoked first VTE (n = 614), no association was observed between THBD polymorphism and risk of VTE recurrence (HR 1.22 and 95 % CI 0.78-1.89, p = 0.38). In this prospective study, our results do not suggest a predictive role for THBD c.1418C>T polymorphism in VTE recurrence. PMID:26743062

  20. Polymorphisms of the LEP- and LEPR gene and obesity in patients using antipsychotic medication.

    PubMed

    Gregoor, Jochem G; van der Weide, Jan; Mulder, Hans; Cohen, Dan; van Megen, Harold J G M; Egberts, Antoine C G; Heerdink, Eibert R

    2009-02-01

    Weight gain is one of the most serious adverse effects of atypical antipsychotic agents. Genetic factors influence the risk of an individual to gain weight. The objective of our study was to determine whether the LEPR Q223R polymorphism and the LEP promoter 2548G/A polymorphism are associated with obesity in a group of male and female patients using atypical antipsychotic drugs. A cross-sectional study design was used. The study population consisted of 200 patients aged between 18 and 65 years, diagnosed with a psychotic disorder, all of whom had been using an atypical antipsychotic for at least 3 months. The primary outcome measure was the presence of obesity. Determinants were the LEPR Q223R (rs1137101) polymorphism and the LEP promoter 2548G/A single nucleotide polymorphism ([SNP] rs7799039). Of the 200 included patients, 61 (31%) were obese. In females, the LEPR 223QR (adjusted odds ratio, 0.11; 95% confidence interval [CI], 0.02-0.54) and LEPR 223RR (adjusted odds ratio, 0.07; 95% CI, 0.01-0.63) genotypes were associated with a lower risk of obesity. In males, this association was not found. In females, the average body weight was 13.6 kg more (95% CI, 1.11-26.1) in the LEPR 223QQ group compared with the LEPR 223RR group. No significant association was found between the LEP promoter 2548G/A polymorphism and obesity. Taken together, the results of our study show that the LEPR Q223R polymorphism may be associated with obesity in women with a psychotic disorder treated with atypical antipsychotic drugs and stress the importance of stratification for gender when investigating the role of variations of the LEP- and LEPR genes on the metabolic side effects of antipsychotic medications. PMID:19142102

  1. Association of Neonatal Hyperbilirubinemia with UGT1A1 Gene Polymorphisms: A Meta-Analysis

    PubMed Central

    Yu, Zibi; Zhu, Kaichang; Wang, Li; Liu, Ying; Sun, Jianmei

    2015-01-01

    Background The results of studies on association between the polymorphisms in the coding region and the promoter of uridine diphosphateglucuronosyl transferase 1A1 (UGT1A1) and neonatal hyperbilirubinemia are controversial. This study aimed to determine whether the UGT1A1 gene polymorphisms of Gly71Arg and TATA promoter were significant risk factors associated with neonatal hyperbilirubinemia. Material/Methods The PubMed, Cochrane Library, and Embase databases were searched for papers that describe the association between UGT1A1 polymorphisms and neonatal hyperbilirubinemia. Summary odds ratios and 95% confidence intervals (CI) were estimated based on a fixed-effects model or random-effects model, depending on the absence or presence of significant heterogeneity. Results A total of 32 eligible studies and 6520 participants were identified. Among them, 24 studies focused on the association of neonatal hyperbilirubinemia with UGT1A1 Gly71Arg polymorphisms, and a significant difference was found for the comparison of AA vs. AG+GG (OR=3.47, 95% CI=2.29–5.28, P<0.0001). We included 19 studies on the association of neonatal hyperbilirubinemia with UGT1A1 TATA promoter polymorphism, which also found a statistically significant difference between 7/7 and 6/7 + 6/6 (OR=2.24, 95% CI=1.29–3.92, P=0.004). Conclusions This meta-analysis demonstrated that UGT1A1 polymorphisms (Gly71Arg and TATA promoter) significantly increase the risk of neonatal hyperbilirubinemia. PMID:26467199

  2. Frequencies of VNTR and RFLP polymorphisms associated with factor VIII gene in Singapore

    SciTech Connect

    Fong, I.; Lai, P.S.; Ouah, T.C.

    1994-09-01

    The allelic frequency of any polymorphism within a population determines its usefulness for genetic counselling. This is important in populations of non-Caucasian origin as RFLPs may significantly differ among ethnic groups. We report a study of five intragenic polymorphisms in factor VIII gene carried out in Singapore. The three PCR-based RFLP markers studied were Intron 18/Bcl I, Intron 19/Hind III and Intron 22/Xba I. In an analysis of 148 unrelated normal X chromosomes, the allele frequencies were found to be A1 = 0.18, A2 = 0.82 (Bcl I RFLP), A1 = 0.80, A2 = 0.20 (Hind III RFLP) and A1 = 0.58, and A2 = 0.42 (Xba I RFLP). The heterozygosity rates of 74 females analyzed separately were 31%, 32% and 84.2%, respectively. Linkage disequilibrium was also observed to some degree between Bcl I and Hind III polymorphism in our population. We have also analyzed a sequence polymorphism in Intron 7 using hybridization with radioactive-labelled {sup 32}P allele-specific oligonucleotide probes. This polymorphism was not very polymorphic in our population with only 2% of 117 individuals analyzed being informative. However, the use of a hypervariable dinucleotide repeat sequence (VNTR) in Intron 13 showed that 25 of our of 27 (93%) females were heterozygous. Allele frequencies ranged from 1 to 55 %. We conclude that a viable strategy for molecular analysis of Hemophilia A families in our population should include the use of Intron 18/Bcl I and Intron 22/Xba I RFLP markers and the Intron 13 VNTR marker.

  3. Meta-Analysis of Ubiquilin1 Gene Polymorphism and Alzheimer’s Disease Risk

    PubMed Central

    Zhang, Tianpeng; Jia, Yingying

    2014-01-01

    Background Some studies have evaluated the association between the Ubiquilin 1 (UBQLN1) gene UBQ-8i polymorphism and Alzheimer’s disease (AD). However, the results remain uncertain. We carried out a meta-analysis to derive a more comprehensive estimation of this association. Material/Methods Case-control studies were identified by searching databases of PubMed, EMBASE, Web of Science, CNKI, CBM, Wanfang, and VIP. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Results The UBQ-8i polymorphism was significantly associated with an increased AD risk (OR=1.15; 95%CI 1.05–1.25; P=0.002). The combination of adjusted ORs also found UBQ-8i polymorphism was significantly associated with AD risk (OR=1.15; 95%CI 1.02–1.30; P=0.02). When stratified by APOE ɛ4 status, both APOE ɛ4 carriers and APOE non-ɛ4 carriers with UBQ-8i polymorphism had significantly increased AD risk (OR=1.28; 95%CI 1.05–1.56; P=0.01 and OR=1.25; 95%CI 1.04–1.50; P=0.02). In the subgroup analysis according to age, UBQ-8i polymorphism was significantly associated with LOAD risk (OR=1.17; 95%CI 1.05–1.31; P=0.005), but not with EOAD risk (OR=1.12; 95%CI 0.95–1.31; P=0.17). Conclusions These results suggest that the UBQ-8i polymorphism is associated with AD risk. PMID:25387430

  4. Polymorphisms in the promoter region of catalase gene and essential hypertension.

    PubMed

    Zhou, Xiao Feng; Cui, Jing; DeStefano, Anita L; Chazaro, Irmarie; Farrer, Lindsay A; Manolis, Athanasios J; Gavras, Haralambos; Baldwin, Clinton T

    2005-01-01

    Genetic variations that predispose individuals to complex disorders, such as essential hypertension, may be found in gene coding regions, intronic regions or in gene promoter regions. Most studies have focused on gene variations that result in amino acid substitutions because they result in different isoforms of the protein, presumably resulting in differences in protein properties. Less attention has been placed on the role of intronic or promoter mutations. In this report, we examined two single nucleotide polymorphisms (SNPs) in the catalase (CAT) gene prompter region in a cohort of hypertensive Caucasians and African Americans with a Mass Spec based Homogenous MassEXTEND assay. We found an association when a specific combination of the two promoter SNPs was examined in Caucasians. No association was observed in African Americans. Our data suggest that genetic variations in the promoter region of catalase gene influence the susceptibility to essential hypertension. In addition, the genetic factors that contribute to hypertension maybe different between ethnic groups. PMID:15735318

  5. Interleukin-18, interleukin-12B and interferon-γ gene polymorphisms in Brazilian patients with rheumatoid arthritis: a pilot study.

    PubMed

    Angelo, H D; Gomes Silva, I I F; Oliveira, R D R; Louzada-Júnior, P; Donadi, E A; Crovella, S; Maia, M M D; de Souza, P R E; Sandrin-Garcia, P

    2015-10-01

    Polymorphisms in interleukin (IL)-18, IL-12 and interferon (IFN)-γ genes are associated with different levels of cytokines expression and have been associated with rheumatoid arthritis (RA). IL-18 +105 A/C, IL-12B +1188 A/C and IFN-γ +874 T/A polymorphisms were analyzed by restriction fragment length polymorphism-polymerase chain reaction (PCR) and amplification refractory mutation system PCR from 90 RA patients and 186 healthy individuals. There were significant differences to IL-18 +105 A/C polymorphism between the RA and control groups (odds ratio = 3.77; P < 0.0001). Individual carriers of the variant allele C had a 3.77-fold increased risk of for RA (P = 0.0032). No association was observed for IL-12B and IFN-γ polymorphisms. Our finds suggest a possible role for IL-18 polymorphism in the RA susceptibility in studied population. PMID:26302971

  6. ASSOCIATIONS BETWEEN POLYMORPHISMS IN DNA REPAIR GENES AND GLIOBLASTOMA

    PubMed Central

    McKean-Cowdin, Roberta; Barnholtz-Sloan, Jill; Inskip, Peter; Ruder, Avima; Butler, MaryAnn; Rajaraman, Preetha; Razavi, Pedram; Patoka, Joe; Wiencke, John; Bondy, Melissa; Wrensch, Margaret

    2009-01-01

    A pooled analysis was conducted to examine the association between select variants in DNA repair genes and glioblastoma multiforme (GBM), the most common and deadliest form of adult brain tumors. Genetic data for approximately 1,000 GBM cases and 2,000 controls were combined from four centers in the United States that have conducted case-control studies of adult GBM including the National Cancer Institute, the National Institute for Occupational Safety and Health, the University of Texas M.D. Anderson Cancer Center, and the University of California at San Francisco. Twelve DNA repair SNPs were selected for investigation in the pilot collaborative project. The C allele of the PARP1 rs1136410 variant was associated with a 20% reduction in risk of GBM (ORCT or CC =0.80; 95%CI 0.67–0.95). A 44% increase in risk of GBM was found for individuals homozygous for the G allele of the PRKDC rs7003908 variant (ORGG 1.44; 95%CI 1.13–1.84); there was a statistically significant trend (p=0.009) with increasing number of G alleles. A significant, protective effect was found when 3 SNPs (ERCC2 rs13181, ERCC1 rs3212986, and GLTSCR1 rs1035938) located near each other on chromosome 19 were modeled as a haplotype. The most common haplotype (AGC) was associated with a 23% reduction in risk (p=0.03) compared to all other haplotypes combined. Few studies have reported on the associations between variants in DNA repair genes and brain tumors, and few specifically have examined their impact on GBMs. Our results suggest that common variation in DNA repair genes may be associated with risk of GBMs. PMID:19318434

  7. Association of Htra1 gene polymorphisms with the risk of developing AMD in Iranian population

    PubMed Central

    Askari, Mohammad; Nikpoor, Amin Reza; Gorjipour, Fazel; Mazidi, Mohsen; Sanati, Mohammad Hosein; Aryan, Hajar; Irani, Alireza; Ghasemi Falavarjani, Khalil; Nazari, Hossein; Mousavizadeh, Kazem

    2015-01-01

    Background: Half of the cases of vision loss in people under 60 years of age have been attributed to age-related macular degeneration (AMD). This is a multifactorial disease with late onset. It has been demonstrated that many different genetic loci are implicated in the risk of developing AMD in different populations. In the current study, we investigated the association of high-temperature ‎requirement A-1 (HTRA1) gene polymorphisms with the risk of developing AMD in the Iranian population. Methods: Genomic DNA samples were extracted from 120 patients with AMD and 120 healthy age- and sex-matched controls. A 385 base-pair fragment of the HTRA1 gene promoter region was amplified using the polymerase chain reaction (PCR) technique and sequenced. The frequencies of the alleles were calculated and statistical analysis was performed using SPSS software. Results: Our study demonstrated that the rate of polymorphisms rs11200638 -625 G>A and rs2672598 -487T>C were significantly greater in AMD patients than in healthy controls from the Iranian population. Conclusions: The results of our study indicate that HTRA1 gene promoter region polymorphisms are associated with the risk of developing AMD in the Iranian population. PMID:26989749

  8. Association of single nucleotide polymorphisms in MPO and COX genes with oral lichen planus.

    PubMed

    Wu, D; Chen, X; Dong, C; Liu, Q; Yang, Y; He, C; Wang, J; Sun, M; Wu, Y

    2015-06-01

    Oral lichen planus (OLP) is an intractable, chronic inflammatory disorder, and its pathogenesis is still largely unknown. Some literatures supported that genes involved in both oxidative stress and prostaglandin metabolism play an important role in the process of inflammation. To explore their association with OLP, we investigated four single nucleotide polymorphisms (SNPs) from myeloperoxidase (MPO) and cyclooxygenase (COX) genes in 475 Chinese individuals (242 case and 233 controls) by MassArray. Although the genotype distributions had no significant differences between the patients and controls, we found that in different gender, rs2243828 from MPO displayed the statistically significant variance genotype frequencies between patients and controls (P = 0.018 in females, P = 0.035 in males). Moreover, for the major allele recessive model, this SNP also showed a significant difference between case and control groups in males (P = 0.015). In this study, we first observed significant association with MPO polymorphism and OLP risk in different gender groups in Chinese, suggesting MPO polymorphism is a gender-specific risk factor of OLP probably by influencing sex hormone-sensitive elements to regulate inflammatory gene expression networks, and we further revealed that oxidative stress was actually involved in the pathogenesis of this disease. Moreover, these findings inspire us some constructive solutions to the treatment of this disease. PMID:25823564

  9. Single nucleotide polymorphisms in DKK3 gene are associated with prostate cancer risk and progression

    PubMed Central

    Kim, Min Su; Lee, Ha Na; Kim, Hae Jong; Myung, Soon Chul

    2015-01-01

    ABSTRACT We had investigated whether sequence variants within DKK3 gene are associated with the development of prostate cancer in a Korean study cohort. We evaluated the association between 53 single nucleotide polymorphisms (SNPs) in the DKK3 gene and prostate cancer risk as well as clinical characteristics (PSA, clinical stage, pathological stage and Gleason score) in Korean men (272 prostate cancer subjects and 173 benign prostate hyperplasia subjects) using unconditional logistic regression analysis. Of the 53 SNPs and 25 common haplotypes, 5 SNPs and 4 haplotypes were associated with prostate cancer risk (P=0.02–0.04); 3 SNPs and 2 haplotypes were significantly associated with susceptibility to prostate cancer, however 2 SNPs and 2 haplotypes exhibited a significant protective effect on prostate cancer. Logistic analyses of the DKK3 gene polymorphisms with several prostate cancer related factors showed that several SNPs were significant; three SNPs and two haplotypes to PSA level, three SNPs and two haplotypes to clinical stage, nine SNPs and two haplotype to pathological stage, one SNP and one haplotypes to Gleason score. To the author's knowledge, this is the first report documenting that DKK3 polymorphisms are not only associated with prostate cancer but also related to prostate cancer-related factors. PMID:26689513

  10. Association between HLA-E gene polymorphism and unexplained recurrent spontaneous abortion (RSA) in Iranian women

    PubMed Central

    Fotoohi, Maryam; Ghasemi, Nasrin; Mirghanizadeh, Seyed Ali; Vakili, Mahmood; Samadi, Morteza

    2016-01-01

    Background: Human leukocyte antigen-E (HLA-E)is a non-classical major histocompatibility complex (MHC) class I antigens which expressed on extra villous cytotrophoblast, which interacts with NKG2A, is an inhibitory receptor on natural killer (NK) cells and leading to down regulation of immune response in the maternal-fetal interface and provides maternal immune tolerance of the fetus. Objective: This study was designated to investigate the gene frequencies of E0101 and E0103 in HLA-E gene in Iranian women with recurrent spontaneous abortion (RSA). Materials and Methods: Amplification Refractory Mutation System (ARMS-PCR) technique was carried out to detect polymorphism in exon 3 of the HLA-E gene in women with RSA and controls (n=200). Differences between groups were analyzed by SPSS19 software using 2 test. Results: There was no significant difference in the allele frequencies of the HLA-E polymorphism between RSA and fertile controls but HLA-E 0101/0103 heterozygous genotype was found to be significantly higher in RSA group (p=0.006, OR=1.73), so this genotype might confer susceptibility to RSA. Conclusion: Our results suggest that HLA-E 0101/0103 heterozygous genotype leads to increase of RSA risk. It seems that by genotyping of HLA-E polymorphism, we can predict the risk of RSA in infertile women. PMID:27525333

  11. A frequent polymorphism in the coding exon of the human cannabinoid receptor (CNR1) gene.

    PubMed

    Gadzicki, D; Müller-Vahl, K; Stuhrmann, M

    1999-08-01

    The central cannabinoid receptor (CB1) mediates the pharmacological activities of cannabis, the endogenous agonist anandamide and several synthetic agonists. The cloning of the human cannabinoid receptor (CNR1) gene facilitates molecular genetic studies in disorders like Gilles de la Tourette syndrome (GTS), obsessive compulsive disorder (OCD), Parkinsons disease, Alzheimers disease or other neuro psychiatric or neurological diseases, which may be predisposed or influenced by mutations or variants in the CNR1 gene. We detected a frequent silent mutation (1359G-->A) in codon 453 (Thr) of the CNR1 gene that turned out to be a common polymorphism in the German population. Allele frequencies of this polymorphism are 0.76 and 0.24, respectively. We developed a simple and rapid polymerase chain reaction (PCR)-based assay by artificial creation of a Msp I restriction site in amplified wild-type DNA (G-allele), which is destroyed by the silent mutation (A-allele). The intragenic CNR1 polymorphism 1359(G/A) should be useful for association studies in neuro psychiatric disorders which may be related to anandamide metabolism disturbances. PMID:10441206

  12. Vitamin D receptor gene polymorphisms are associated with breast cancer risk in a UK Caucasian population.

    PubMed

    Bretherton-Watt, D; Given-Wilson, R; Mansi, J L; Thomas, V; Carter, N; Colston, K W

    2001-07-20

    There is increasing evidence that vitamin D can protect against breast cancer. The actions of vitamin D are mediated via the vitamin D receptor (VDR). We have investigated whether polymorphisms in the VDR gene are associated with altered breast cancer risk in a UK Caucasian population. We recruited 241 women following a negative screening mammogram and 181 women with known breast cancer. The VDR polymorphism Bsm I, an intronic 3' gene variant, was significantly associated with increased breast cancer risk: odds ratio bb vs BB genotype = 2.32 (95% CI, 1.23-4.39). The Bsm I polymorphism was in linkage disequilibrium with a candidate translational control site, the variable length poly (A) sequence in the 3' untranslated region. Thus, the 'L' poly (A) variant was also associated with a similar breast cancer risk. A 5' VDR gene variant, Fok I, was not associated with breast cancer risk. Further investigations into the mechanisms of interactions of the VDR with other environmental and/or genetic influences to alter breast cancer risk may lead to a new understanding of the role of vitamin D in the control of cellular and developmental pathways. PMID:11461072

  13. Uremic Pruritus Is Not Associated with Endocannabinoid Receptor 1 Gene Polymorphisms

    PubMed Central

    Heisig, Monika; Łaczmański, Łukasz; Reich, Adam; Lwow, Felicja

    2016-01-01

    Uremic pruritus (UP) is a frequent and bothersome symptom in hemodialysis patients. Its etiology is not fully understood and that is why there is no specific treatment. The endocannabinoid system plays a role in many pathological conditions. There is reliable evidence on the association between cannabinoid system and pruritus. In our study, we aimed to evaluate whether genetic variations in the endocannabinoid receptor 1 (CNR1) gene can affect UP. The rs12720071, rs806368, rs1049353, rs806381, rs10485170, rs6454674, and rs2023239 polymorphisms of the CNR1 gene were genotyped in 159 hemodialysis patients and 150 healthy controls using two multiplex polymerase chain reactions and the minisequencing technique. No statistically significant relationship was found in any of the evaluated genotypes between patients with and without UP, even after excluding patients with diabetes and dyslipidemia. There were no differences between patients with UP and the control group. However, in the group of all HD patients, a significantly higher incidence of GA genotype and lower incidence in GG genotype in the polymorphism rs806381s were revealed versus the control group (p = 0.04). It seems that polymorphisms of the CNR1 gene are not associated with uremic pruritus. PMID:27034934

  14. Association of the NOTCH4 Gene Polymorphism rs204993 with Schizophrenia in the Chinese Han Population.

    PubMed

    Zhang, Bao; Fan, Qian Rui; Li, Wen Hao; Lu, Ning; Fu, Dong Ke; Kang, Yan Jie; Wang, Na; Li, Teng; Wen, Xiao Peng; Li, Da Xu

    2015-01-01

    NOTCH4 regulates signaling pathways associated with neuronal maturation, a process involved in the development and patterning of the central nervous system. The NOTCH4 gene has also been identified as a possible susceptibility gene for schizophrenia (SCZ). The objective of this study was to examine the relationship between NOTCH4 polymorphisms and SCZ in the Chinese Han population. The rs2071287 and rs204993 polymorphisms of the NOTCH4 gene were analyzed in 443 patients with SCZ and 628 controls of Han Chinese descent. Single SNP allele-, genotype-, and gender-specific associations were analyzed using different models (i.e., additive, dominant, and recessive models). This association study revealed that the rs204993 polymorphism is significantly associated with susceptibility for SCZ and that the AA genotype of rs204993 is associated with a higher risk for SCZ (P = 0.027; OR = 1.460; 95% CI, 1.043-2.054). Our data are consistent with those obtained in previous studies that suggested that rs204993 is associated with SCZ and that the AA genotype of rs204993 demonstrates a higher risk. Further large-scale association analyses in Han Chinese populations are warranted. PMID:26605328

  15. Methylenetetrahydrofolate reductase C677T gene polymorphism in Turkish patients with polycystic ovary syndrome.

    PubMed

    Karadeniz, Muammer; Erdogan, Mehmet; Zengi, Ayhan; Eroglu, Zuhal; Tamsel, Sadik; Olukman, Murat; Saygili, Fusun; Yilmaz, Candeger

    2010-08-01

    Higher Levels of Hcy are associated with several clinical conditions, among them non-insulin-dependent diabetes mellitus, endometrial dysplasia and hypertension with insulin resistance, and polycystic ovary syndrome. The purpose of this study was to investigate the serum homocystein levels and other metabolic parameters in relationship with the MTHFR C677T gene polymorphism in patients with PCOS. Our study included 86 young women with PCOS constituting the study group and 70 healthy women constituting the control group. Homocystein levels, metabolic, and hormonal parameters were measured, and genetic analysis of the MTHFR C677T gene polymorphism was performed in all the subjects. A statistically significant difference was observed in mean homocystein levels between patients with PCOS when compared to the control group. The MTHFR 677 CC genotypes had significantly higher proportions in the control group compared to the PCOS patients (χ(2) = 21.381, P < 0.001). Our data show that homocystein levels were higher than normal subjects in patients with PCOS and that the MTHFR C677T gene polymorphism does not influence homocystein levels of patients with PCOS. PMID:20960113

  16. Association between the MTHFR C677T gene polymorphism and essential hypertension in South West Cameroon.

    PubMed

    Ghogomu, S M; Ngolle, N E; Mouliom, R N; Asa, B F

    2016-01-01

    The association of the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and essential hypertension has been reported but with controversial results in diverse populations in Asia and Europe, thereby suggesting a dependency on ethnicity. The aim of this study was to investigate the association between the MTHFR C677T polymorphism and essential hypertension in a Cameroonian population (Bantu ethnic group) of the South West Region. Analysis of anthropometric and biochemical data in hypertensive and normotensive subjects revealed that age, systolic blood pressure, diastolic blood pressure, low-density lipoprotein cholesterol, serum total cholesterol, and triglycerides are independent risk factors for essential hypertension. Substitution of thymine for cytosine at position 667 of the MTHFR gene was determined by polymerase chain reaction-restriction fragment length polymorphism. Genotype frequencies were found to be 7.3% CC, 58.5% CT, and 34.1% TT for hypertensive subjects compared to 90.0% CC, 10.0% CT, and 0.0% TT for normotensives. Allele frequencies were obtained as 36.6% C and 63.4% T for hypertensive subjects and 95.0% C and 5.0% T for normotensive subjects. These results reveal that the T allele predisposes individuals to hypertension. Therefore, there is an association between variants of the MTHFR gene and hypertension in Cameroonian patients from the South West region. PMID:27051013

  17. Polymorphisms of the DNA Methyltransferase 1 Gene Predict Survival of Gastric Cancer Patients Receiving Tumorectomy

    PubMed Central

    Jia, Zhifang; Wu, Xing; Cao, Donghui; Wang, Chuan; You, Lili; Jin, Meishan; Wen, Simin; Cao, Xueyuan; Jiang, Jing

    2016-01-01

    DNA methyltransferase 1 (DNMT1) plays a pivotal role in maintaining DNA methylation status. Polymorphisms of DNMT1 may modify the role of DNMT1 in prognosis of gastric cancer (GC). Our aim was to test whether polymorphisms of DNMT1 gene were associated with overall survival of GC. Four hundred and forty-seven GC patients who underwent radical tumorectomy were enrolled in the study. Five tagging SNPs (rs10420321, rs16999593, rs2228612, rs2228611, and rs2288349) of the DNMT1 gene were genotyped by TaqMan assays. Kaplan-Meier survival plots and Cox proportional hazard regression were used to analyze the associations between SNPs of DNMT1 and survival of GC. Patients carrying rs2228611 GA/AA genotype tended to live longer than those bearing the GG genotype (HR 0.68, 95% CI: 0.51–0.91, P = 0.007). Further multivariate Cox regression analysis showed that rs2228611 was an independent prognostic factor (GA/AA versus GG: OR 0.67, 95% CI 0.49–0.91, P = 0.010). Nevertheless, other SNPs did not show any significant associations with survival of GC. Polymorphisms of the DNMT1 gene may affect overall survival of GC. The SNP rs2228611 has the potentiality to serve as an independent prognostic marker for GC patients. PMID:27087738

  18. Effect of serotonin receptor 2A gene polymorphism on mirtazapine response in major depression.

    PubMed

    Kang, Rhee-Hun; Choi, Myoung-Jin; Paik, Jong-Woo; Hahn, Sang-Woo; Lee, Min-Soo

    2007-01-01

    The 5-HTR2A gene is a candidate gene for influencing the clinical response to treatment with antidepressants. The purpose of this study was to determine the relationship between the -1438A/G polymorphism of the 5-HTR2A gene and the response to mirtazapine in a Korean population with major depressive disorder. Mirtazapine was administered for eight weeks to the 101 patients who completed the study, during which we evaluated the clinical outcome using repeated-measures ANCOVA. A main effect of genotype or an effect of genotype-time interactions on the decrease in HAMD score during the eight-week follow-up was not found, which suggests that the 5-HTR2A -1438A/G polymorphism does not affect the clinical outcome to mirtazapine administration. However, significant effects of genotype and allele carriers on the decrease in the sleep score over the eight weeks were found (genotype: F = 4.093, p = 0.017; allele: F = 4.371, p = 0.037), whereas no effect of genotype-time interactions on the decrease in the HAMD score over the eight-week follow-up was found. These observations suggest that the -1438A/G polymorphism on the sleep improvement at each time period revealed significant differences in the sleep scores after two weeks of mirtazapine administration. The sleep scores were lower for carriers of the A+ allele than of the A- allele after two weeks of mirtazapine administration (p = 0.041), which means that the -1438GG genotype is associated with less improvement in sleep, and suggests that the effect of mirtazapine on improving the sleep quality differs with the 5-HTR2A -1438A/G polymorphism within two weeks of mirtazapine treatment. In conclusion, although the -1438A/G polymorphism affects the sleep improvement resulting from the administration of mirtazapine to Korean patients with major depressive disorder, our results do not support the hypothesis that this polymorphism of the 5-HTR2A gene is involved in the therapeutic response to mirtazapine. PMID:18314859

  19. The Role of Interleukin-6 and Interleukin-8 Gene Polymorphisms in Non-Alcoholic Steatohepatitis

    PubMed Central

    Cengiz, Mustafa; Yasar, Demet Gokalp; Ergun, Mehmet Ali; Akyol, Gulen; Ozenirler, Seren

    2014-01-01

    Background: Genetic polymorphisms may play role in the pathophysiology of nonalcoholic steatohepatitis (NASH). Objectives: We purposed to assess the role of interleukin 6 (IL 6) and interleukin 8 (IL 8) gene polymorphisms in the pathogenesis of NASH. Patients and Methods: Consecutive patients with biopsy proven NASH and age- and gender-matched healthy individuals with normal liver function tests and normal ultrasonography were enrolled in the study. Histopathological findings were recorded according to nonalcoholic fatty liver disease activity score (NAS). Patients were classified according to fibrosis scores as fibrosis score < 2 (mild fibrosis group) and fibrosis score ≥ 2 (significant fibrosis group). Blood samples were collected and genomic DNA isolation kit was used to evaluate genetic polymorphisms. Results: Of thirty-eight patients, 27 (71%) were in mild fibrosis group and 11 (29%) in significant fibrosis group. Thirty-eight age- and gender-matched healthy controls were enrolled in the study. The frequencies of genotypes G/C and G/G of IL 6 among the NASH group and healthy controls were 39.5% and 60.5% vs. 53.6% and 46.4%, respectively (P = 0.32). The frequencies of the genotypes of IL 8 among the NASH group were 47.2%, 44.6%, and 8.2% for T/T, A/T, and A/A, and in healthy controls were 50%, 28.6% and 21.4%, respectively, (P = 0.568). The differences between IL 8 gene T/A and T/T genotypes were not significant statistically (P > 0.05). However, the frequency of A/A genotype in significant fibrosis group was higher than the mild fibrosis group (P = 0.0016). The differences of -251 A/T polymorphism in the IL 8 and -174 C/G polymorphism in the IL 6 were not statistically significant between fibrosis groups (P > 0.05). Conclusions: IL6 and IL8 gene polymorphisms have no role in NASH pathogenesis and liver fibrosis process, but presence of the A/A genotype in the IL8 gene is associated with disease progression. PMID:25737730

  20. MicroRNA Gene Polymorphisms and Environmental Factors Increase Patient Susceptibility to Hepatocellular Carcinoma

    PubMed Central

    Chu, Yin-Hung; Hsieh, Ming-Ju; Chiou, Hui-Ling; Liou, Yi-Sheng; Yang, Chen-Chieh; Yang, Shun-Fa; Kuo, Wu-Hsien

    2014-01-01

    Background Micro RNAs (miRNAs) are small RNA fragments that naturally exist in the human body. Through various physiological mechanisms, miRNAs can generate different functions for regulating RNA protein levels and balancing abnormalities. Abnormal miRNA expression has been reported to be highly related to several diseases and cancers. Single-nucleotide polymorphisms (SNPs) in miRNAs have been reported to increase patient susceptibility and affect patient prognosis and survival. We adopted a case-control research design to verify the relationship between miRNAs and hepatocellular carcinoma. Methodology/Principal Findings A total of 525 subjects, including 377 controls and 188 hepatocellular carcinoma patients, were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and real-time PCR were used to analyze miRNA146a (rs2910164), miRNA149 (rs2292832), miRNA196 (rs11614913), and miRNA499 (rs3746444) genetic polymorphisms between the control group and the case group. The results indicate that people who carry the rs3746444 CT or CC genotypes may have a significantly increased susceptibility to hepatocellular carcinoma (adjusted odds ratio [AOR] = 2.84, 95% confidence interval [CI] = 1.88–4.30). In addition, when combined with environmental risk factors, such as smoking and alcohol consumption, interaction effects were observed between gene polymorphisms and environmental factors (odds ratio [OR] = 4.69, 95% CI = 2.52–8.70; AOR = 3.38, 95% CI = 1.68–6.80). Conclusions These results suggest that a significant association exists between miRNA499 SNPs and hepatocellular carcinoma. Gene-environment interactions of miRNA499 polymorphisms, smoking, and alcohol consumption might alter hepatocellular carcinoma susceptibility. PMID:24587132

  1. Two novel mutations and a previously unreported intronic polymorphism in the NOTCH3 gene.

    PubMed

    Roy, B; Maksemous, N; Smith, R A; Menon, S; Davies, G; Griffiths, L R

    2012-04-01

    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disease of small vessel caused by mutations in the NOTCH3 gene (NCBI Gene ID: 4854) located on chromosome 19p13.1. NOTCH3 consists of 33 exons which encode a protein of 2321 amino acids. Exons 3 and 4 were found to be mutation hotspots, containing more than 65% of all CADASIL mutations. We performed direct sequencing on an ABI 3130 Genetic Analyser to screen for mutations and polymorphisms on 300 patients who were clinically suspected to have CADASIL. First, exons 3 and 4 were screened in NOTCH3 and if there were no variations found, then extended CADASIL testing (exons 2, 11, 18 and 19) was offered to patients. Here we report two novel non-synonymous mutations identified in the NOTCH3 gene. The first mutation, located in exon 4 was found in a 49-year-old female and causes an alanine to valine amino acid change at position 202 (605C>T). The second mutation, located in exon 11, was found in a 66-year-old female and causes a cysteine to arginine amino acid change at position 579 (1735T>C). We also report a 46-year-old male with a known polymorphism Thr101Thr (rs3815188) and an unreported polymorphism NM_000435.2:c.679+60G>A observed in intron 4 of the NOTCH3 gene. Although Ala202Ala (rs1043994) is a common polymorphism in the NOTCH3 gene, our reported novel mutation (Ala202Val) causes an amino acid change at the same locus. Our other reported mutation (Cys579Arg) correlates well with other known mutations in NOTCH3, as the majority of the CADASIL-associated mutations in NOTCH3 generally occur in the EGF-like (epidermal growth factor-like) repeat domain, causing a change in the number of cysteine residues. The intronic polymorphism NM_000435.2:c.679+60G>A lies close to the intron-exon boundary and may affect the splicing mechanism in the NOTCH3 gene. PMID:22373597

  2. Mutual Regulation of Epicardial Adipose Tissue and Myocardial Redox State by PPAR-γ/Adiponectin Signalling

    PubMed Central

    Antonopoulos, Alexios S.; Margaritis, Marios; Verheule, Sander; Recalde, Alice; Sanna, Fabio; Herdman, Laura; Psarros, Costas; Nasrallah, Hussein; Coutinho, Patricia; Akoumianakis, Ioannis; Brewer, Alison C.; Sayeed, Rana; Krasopoulos, George; Petrou, Mario; Tarun, Akansha; Tousoulis, Dimitris; Shah, Ajay M.; Casadei, Barbara; Channon, Keith M.

    2016-01-01

    Rationale: Adiponectin has anti-inflammatory effects in experimental models, but its role in the regulation of myocardial redox state in humans is unknown. Although adiponectin is released from epicardial adipose tissue (EpAT), it is unclear whether it exerts any paracrine effects on the human myocardium. Objective: To explore the cross talk between EpAT-derived adiponectin and myocardial redox state in the human heart. Methods and Results: EpAT and atrial myocardium were obtained from 306 patients undergoing coronary artery bypass grafting. Functional genetic polymorphisms that increase ADIPOQ expression (encoding adiponectin) led to reduced myocardial nicotinamide adenine dinucleotide phosphate oxidase–derived O2−, whereas circulating adiponectin and ADIPOQ expression in EpAT were associated with elevated myocardial O2−. In human atrial tissue, we demonstrated that adiponectin suppresses myocardial nicotinamide adenine dinucleotide phosphate oxidase activity, by preventing AMP kinase–mediated translocation of Rac1 and p47phox from the cytosol to the membranes. Induction of O2− production in H9C2 cardiac myocytes led to the release of a transferable factor able to induce peroxisome proliferator-activated receptor-γ–mediated upregulation of ADIPOQ expression in cocultured EpAT. Using a NOX2 transgenic mouse and a pig model of rapid atrial pacing, we found that oxidation products (such as 4-hydroxynonenal) released from the heart trigger peroxisome proliferator-activated receptor-γ–mediated upregulation of ADIPOQ in EpAT. Conclusions: We demonstrate for the first time in humans that adiponectin directly decreases myocardial nicotinamide adenine dinucleotide phosphate oxidase activity via endocrine or paracrine effects. Adiponectin expression in EpAT is controlled by paracrine effects of oxidation products released from the heart. These effects constitute a novel defense mechanism of the heart against myocardial oxidative stress. PMID:26838789

  3. Association of G197 polymorphism of IL-17A gene with myocardial remodeling and aerobic performance in athletes.

    PubMed

    Lifanov, A D; Khadyeva, M N; Demenev, S V; Knyazev, A N; Babushkin, Yu A; Astashina, E E

    2014-09-01

    We studied the relationship between G197A polymorphism of IL-17A gene and changes in morphometric echocardiography parameters and physiological parameters in skiers (19 examinees). Genotyping was performed by restriction fragment length polymorphism analysis and echocardiography using a Nemio MX ultrasound scanner (Toshiba). Association of 197A allele of IL-17A gene with low myocardial growth and high aerobic performance of athletes was demonstrated. PMID:25257435

  4. Association of ATP1A1 gene polymorphism with thermotolerance in Tharparkar and Vrindavani cattle

    PubMed Central

    Kashyap, Neeraj; Kumar, Pushpendra; Deshmukh, Bharti; Bhat, Sandip; Kumar, Amit; Chauhan, Anuj; Bhushan, Bharat; Singh, Gyanendra; Sharma, Deepak

    2015-01-01

    Aim: One of the major biochemical aspects of thermoregulation is equilibrium of ion gradient across biological membranes. Na+/K+-ATPase, a member of P type-ATPase family, is a major contributor to the mechanism that actively controls cross-membrane ion gradient. Thus, we examined ATP1A1 gene that encodes alpha-1 chain of Na+/K+-ATPase, for genetic polymorphisms. Materials and Methods: A total of 100 Vrindavani (composite cross strain of Hariana x Holstein-Friesian/Brown Swiss/Jersey) and 64 Tharparkar (indigenous) cattle were screened for genetic polymorphism in ATP1A1 gene, using polymerase chain reaction single-strand conformation polymorphism and DNA sequencing. For association studies, rectal temperature (RT) and respiration rate (RR) of all animals were recorded twice daily for 3 seasons. Results: A SNP (C2789A) was identified in exon 17 of ATP1A1 gene. Three genotypes namely CC, CA, and AA were observed in both, Vrindavani and Tharparkar cattle. The gene frequencies in Tharparkar and Vrindavani for allele A were 0.51 and 0.48, and for allele C were 0.49 and 0.52, respectively, which remained at intermediate range. Association study of genotypes with RT and RR in both cattle population revealed that the animals with genotype CC exhibited significantly lower RT and higher heat tolerance coefficient than CA and AA genotypes. Conclusion: Differential thermoregulation between different genotypes of ATP1A1 gene indicate that the ATP1A1 gene could be potentially contributing to thermotolerance in both, Tharparkar, an indigenous breed and Vrindavani, a composite crossbred cattle. PMID:27047171

  5. HLA, NFKB1 and NFKBIA gene polymorphism profile in autoimmune diabetes mellitus patients.

    PubMed

    Katarina, K; Daniela, P; Peter, N; Marianna, R; Pavlina, C; Stepanka, P; Jan, L; Ludmila, T; Michal, A; Marie, C

    2007-02-01

    Type 1 diabetes mellitus (T1DM) is one of the long-time studied autoimmune disorders. The triggering of the autoimmune process has been ascribed to various genes active in the regulation of the cytokine gene transcription including the Rel/NF-kappaB gene family. In our study the gene polymorphism of HLA class II, NFKB1 (nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) and NFKBIA (inhibitor of nuclear factor kappa B) was tested. Patients were divided into the subgroups in relation to the disease type: T1DM in children, T1DM in adults, and Latent Autoimmune Diabetes in Adults (LADA). HLA-DRB1 (*)04 and HLA-DQB1 (*)0302 have been detected as risk factors for T1DM in adults and particularly in children (P<0.0001, OR=22.9 and 46.5 respectively). HLA-DRB1 (*)03 has been found as a single risk factor for LADA (P<0.0001, OR=4.9). We detected 15 alleles for the NFKB1 gene polymorphism (CA-repeats) in the Czech population. The alleles were ranging in size from 114-142 bp corresponding to 10-25 CA repeats. Frequency of the A7 allele of NFKB1 gene has been significantly increased in T1DM adults (P<0.01). There was no difference in A and a G allele frequency of NFKBIA gene between the control group and patients, but the association of the AA genotype of NFKBIA gene has been found for LADA (P<0.05). Summarizing our results we concluded that there is a high probability of association of gene polymorphism from Rel/NF-kappaB family with an autoimmune diabetes course. Due to the results obtained in the epidemiological study we have been looking also for the function significance of the genetic predisposition. No significant changes have been observed by real time PCR testing of HLA-DRB1 (*)04 gene and NFKB1 gene expression between T1DM diabetic group with different HLA, NFKB1, NFKBIA genetic background. PMID:17318773

  6. Combination effect of cytochrome P450 1A1 gene polymorphisms on uterine leiomyoma: A case-control study.

    PubMed

    Salimi, Saeedeh; Sajadian, Mojtaba; Khodamian, Maryam; Yazdi, Atefeh; Rezaee, Soodabeh; Mohammadpour-Gharehbagh, Abbas; Mokhtari, Mojgan; Yaghmaie, Minoo

    2016-08-01

    Uterine leiomyoma (UL) is an estrogen-dependent neoplasm of the uterus, and estrogen metabolizing enzymes affect its progression. This study aimed to evaluate the association between two single-nucleotide polymorphisms of cytochrome P450 1A1 (CYP1A1) gene and UL risk. The study consisted of 105 patients with UL and 112 healthy women as controls. Ile462Val (A/G) and Asp449Asp (T/C) polymorphisms of CYP1A1 gene were analyzed by DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism methods, respectively. The findings indicated no association between Ile462Val (A/G) and Asp449Asp (T/C) polymorphisms of CYP1A1 gene and UL (p < 0.05). However, the combination effect of TT/AG genotypes of the Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms was associated with 4.3-fold higher risk of UL. In addition, haplotype analysis revealed that TG haplotype of the Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms could increase the UL risk nearly 4.9-fold. Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms of CYP1A1 gene were not associated with UL susceptibility; however, the combination of the TT/AG genotypes and TG haplotype could increase the UL risk. PMID:27333216

  7. Combination effect of cytochrome P450 1A1 gene polymorphisms on uterine leiomyoma: A case-control study

    PubMed Central

    Salimi, Saeedeh; Sajadian, Mojtaba; Khodamian, Maryam; Yazdi, Atefeh; Rezaee, Soodabeh; Mohammadpour-Gharehbagh, Abbas; Mokhtari, Mojgan; Yaghmaie, Minoo

    2016-01-01

    Uterine leiomyoma (UL) is an estrogen-dependent neoplasm of the uterus, and estrogen metabolizing enzymes affect its progression. This study aimed to evaluate the association between two single-nucleotide polymorphisms of cytochrome P450 1A1 (CYP1A1) gene and UL risk. The study consisted of 105 patients with UL and 112 healthy women as controls. Ile462Val (A/G) and Asp449Asp (T/C) polymorphisms of CYP1A1 gene were analyzed by DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism methods, respectively. The findings indicated no association between Ile462Val (A/G) and Asp449Asp (T/C) polymorphisms of CYP1A1 gene and UL (p < 0.05). However, the combination effect of TT/AG genotypes of the Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms was associated with 4.3-fold higher risk of UL. In addition, haplotype analysis revealed that TG haplotype of the Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms could increase the UL risk nearly 4.9-fold. Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms of CYP1A1 gene were not associated with UL susceptibility; however, the combination of the TT/AG genotypes and TG haplotype could increase the UL risk.

  8. Combination effect of cytochrome P450 1A1 gene polymorphisms on uterine leiomyoma: A case-control study.

    PubMed

    Salimi, Saeedeh; Sajadian, Mojtaba; Khodamian, Maryam; Yazdi, Atefeh; Rezaee, Soodabeh; Mohammadpour-Gharehbagh, Abbas; Mokhtari, Mojgan; Yaghmaie, Minoo

    2016-08-01

    Uterine leiomyoma (UL) is an estrogen-dependent neoplasm of the uterus, and estrogen metabolizing enzymes affect its progression. This study aimed to evaluate the association between two single-nucleotide polymorphisms of cytochrome P450 1A1 (CYP1A1) gene and UL risk. The study consisted of 105 patients with UL and 112 healthy women as controls. Ile462Val (A/G) and Asp449Asp (T/C) polymorphisms of CYP1A1 gene were analyzed by DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism methods, respectively. The findings indicated no association between Ile462Val (A/G) and Asp449Asp (T/C) polymorphisms of CYP1A1 gene and UL (p < 0.05). However, the combination effect of TT/AG genotypes of the Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms was associated with 4.3-fold higher risk of UL. In addition, haplotype analysis revealed that TG haplotype of the Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms could increase the UL risk nearly 4.9-fold. Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms of CYP1A1 gene were not associated with UL susceptibility; however, the combination of the TT/AG genotypes and TG haplotype could increase the UL risk. PMID:27483179

  9. Pro- and anti-inflammatory cytokine gene single-nucleotide polymorphisms in inflammatory bowel disease.

    PubMed

    López-Hernández, R; Valdés, M; Campillo, J A; Martínez-García, P; Salama, H; Bolarin, J M; Martínez, H; Moya-Quiles, M R; Minguela, A; Sánchez-Torres, A; Botella, C; Salgado, G; Miras, M; Carballo, F; Muro, M

    2015-02-01

    Anti-inflammatory cytokines have an important role in disease, tumour and transplant processes. Alterations in the regulation of several cytokines have been implicated in a variety of inflammatory disorders, including IBD (inflammatory bowel disease) [Crohn's disease (CD) and ulcerative colitis (UC)]. Cytokine polymorphisms are also known to affect the level of gene expression. Thus, the aim of this study was to determine the relationship between cytokine polymorphisms and the IBD pathologies in a Spanish population. Polymorphisms analysis was performed using PCR-SSOP using a microbeads luminex assay. The following polymorphisms were determined: TNFα [-238G/A (rs361525) and -308G/A (rs1800629)], IFNγ [+874A/T (rs62559044)], TGFβ [+869C/T (rs1982073) and +915G/C (rs1800471)], IL10 [-1082A/A (rs1800896), -592A/C (rs1800872), -819C/T (rs1800871)], IL6 [-174C/G (rs1800795)], IL12p40 [3'UTR -1188A/C (rs3212227)], IL1α [-889C/T (rs1800587)], IL1β [-511C/T (rs1143634) and +3962C/T (rs1143633)], IL1R [Pst-1 1970C/T] and IL1RA [Mspa-1 11100C/T]. No statistical differences in TNFα, IFNγ, TGFβ, IL10, IL6, IL1α, IL1β, IL1R and IL1Ra genotypes and allele distributions between the IBD groups and healthy controls were found. However, we observed significant differences in the 3'UTR -1188A/C polymorphism of IL12p40. So -1188A allele was increased in patients with UC and the -1188C allele (high IL12p40 production) was increased in patients with CD with respect to controls. These data are in concordance with the fact that CD has been shown to be associated with a Th1 T-cell-mediated inflammation model and high IL12/IFNγ production at histological affected sites. These data suggest that cytokine polymorphisms in TNFα, IFNγ, TGFβ, IL10, IL6 and IL1α, IL1β, IL1R and IL1Ra cytokine gene do not seem to be relevant in IBD susceptibility and IL12p40 3'UTR -1188A/C polymorphism seems to be associated with a differential IBD development. PMID:25359546

  10. Association between Single Nucleotide Polymorphism of Vitamin D Receptor Gene FokI Polymorphism and Clinical Progress of Benign Prostatic Hyperplasia

    PubMed Central

    Ruan, Li; Zhu, Jian-guo; Pan, Cong; Hua, Xing; Yuan, Dong-bo; Li, Zheng-ming; Zhong, Wei-de

    2015-01-01

    Background. The aim of the study was to investigate the association between single nucleotide polymorphism (SNP) of vitamin D receptor (VDR) gene and clinical progress of benign prostatic hyperplasia (BPH) in Chinese men. Methods. The DNA was extracted from blood of 200 BPH patients with operation (progression group) and 200 patients without operation (control group), respectively. The genotypes of VDR gene FokI SNP represented by “F/f” were identified by PCR-restriction fragment length polymorphism. The odds ratio (OR) of having progression of BPH for having the genotype were calculated. Results. Our date indicated that the f alleles of the VDR gene FokI SNP associated with the progression of BPH (P = 0.009). Conclusion. For the first time, our study demonstrated that VDR gene FokI SNP may be associated with the risk of BPH progress. PMID:25685834

  11. Association between TNFA Gene Polymorphisms and Helicobacter pylori Infection: A Meta-Analysis

    PubMed Central

    Sun, Xudong; Xu, Yuanyuan; Wang, Li; Zhang, Fuhua; Zhang, Jinhua; Fu, Ximei; Jing, Tao; Han, Jian

    2016-01-01

    Background Several host genetic factors are thought to affect susceptibility to Helicobacter pylori infection-related diseases, including tumor necrosis factor (TNF)-α. Previous studies have evaluated the association between TNFA gene polymorphisms and H. pylori infection, but the results were inconclusive. We conducted this meta-analysis to clarify the association between TNFA polymorphisms and H. pylori infection. Methods Published literature within PubMed, Embase, and the Cochrane Library were used in our meta-analysis. Data were analyzed with the Stata13.1 software package using pooled odds ratios (ORs) with 95% confidence intervals (CI). Results A total of 24 studies were included in our study. The TNFA -308G>A polymorphism was associated with decreasing H. pylori infection (AA vs. AG+GG, OR = 0.64, 95% CI = 0.43–0.97; AA vs. GG, OR = 0.64, 95% CI = 0.43–0.97). A significantly decreased risk was also found for -1031T>C polymorphism (CC vs. CT+TT, OR = 0.61, 95% CI = 0.44–0.84). -863C>A polymorphism was associated with increasing risk of H. pylori infection (AA+AC vs. CC, OR = 1.47, 95% CI = 1.16–1.86; A allele vs. C allele, OR = 1.40, 95% CI = 1.14–1.72). There was no significant association between -857C>T polymorphism and H. pylori infection. When stratified analysis was conducted on H. pylori infection detection methods, -857C>T and -863C>A polymorphisms were associated with H. pylori infection for the non-ELISA subgroup. When stratified for ethnicity or study design, -863C>A significantly increased the risk and -1031T>C decreased the risk for the Asian subgroup and hospital-based subgroup. Conclusion Results of our meta-analysis demonstrate that TNFA -308G>A and -1031 T>C polymorphisms may be protective factors against H. pylori infection, and -863C>A may be a risk factor, especially in Asian populations. Further studies with larger sample sizes are required to validate these results. PMID:26815578

  12. Association of NER pathway gene polymorphisms with susceptibility to laryngeal cancer in a Chinese population.

    PubMed

    Sun, Yanan; Tan, Lijun; Li, Huijun; Qin, Xiaowei; Liu, Jiangtao

    2015-01-01

    We systematically analyzed the association of nine SNPs of seven key NER pathway genes with the development of laryngeal cancer patients, and investigated whether NER pathway polymorphisms could serve as potential biomarkers for laryngeal cancer risk. 271 patients with pathologically proven laryngeal cancer and 271 control subjects were included in our study. Genotyping of ERCC1 rs11615 and rs2298881, ERCC2 rs13181 and rs50871, ERCC3 rs4150441, ERCC4 rs6498486, ERCC5 rs2094258, XPA rs2808668 and XPC rs2228001 were analyzed by polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). By conditional logistic regression analysis, individuals carrying the TT genotype of ERCC1 rs11615 were correlated with an increased risk of larynx cancer when compared with the CC genotype (OR=1.89, 95% CI=1.07-3.37; P value=0.02). Moreover, individuals with the GG genotype of ERCC2 rs50871 were associated with an elevated risk of larynx cancer when compare with the TT genotype (OR=2.03, 95% CI=1.15-3.63; P value=0.01). We found a significant interaction between ERCC2 rs50871 polymorphism and tobacco smoking in the risk of larynx cancer (P for interaction <0.05). In conclusion, our study showed that ERCC1 rs11615 and ERCC2 rs50871 polymorphisms could influence the risk of larynx cancer in Chinese population, particularly among smokers. PMID:26617899

  13. Association of NER pathway gene polymorphisms with susceptibility to laryngeal cancer in a Chinese population

    PubMed Central

    Sun, Yanan; Tan, Lijun; Li, Huijun; Qin, Xiaowei; Liu, Jiangtao

    2015-01-01

    We systematically analyzed the association of nine SNPs of seven key NER pathway genes with the development of laryngeal cancer patients, and investigated whether NER pathway polymorphisms could serve as potential biomarkers for laryngeal cancer risk. 271 patients with pathologically proven laryngeal cancer and 271 control subjects were included in our study. Genotyping of ERCC1 rs11615 and rs2298881, ERCC2 rs13181 and rs50871, ERCC3 rs4150441, ERCC4 rs6498486, ERCC5 rs2094258, XPA rs2808668 and XPC rs2228001 were analyzed by polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). By conditional logistic regression analysis, individuals carrying the TT genotype of ERCC1 rs11615 were correlated with an increased risk of larynx cancer when compared with the CC genotype (OR=1.89, 95% CI=1.07-3.37; P value=0.02). Moreover, individuals with the GG genotype of ERCC2 rs50871 were associated with an elevated risk of larynx cancer when compare with the TT genotype (OR=2.03, 95% CI=1.15-3.63; P value=0.01). We found a significant interaction between ERCC2 rs50871 polymorphism and tobacco smoking in the risk of larynx cancer (P for interaction <0.05). In conclusion, our study showed that ERCC1 rs11615 and ERCC2 rs50871 polymorphisms could influence the risk of larynx cancer in Chinese population, particularly among smokers. PMID:26617899

  14. Vitamin D receptor gene polymorphisms and musculoskeletal injuries in professional football players

    PubMed Central

    MASSIDDA, MYOSOTIS; CORRIAS, LAURA; BACHIS, VALERIA; CUGIA, PAOLO; PIRAS, FRANCESCO; SCORCU, MARCO; CALÒ, CARLA M.

    2015-01-01

    The aim of the present study was to investigate the association between vitamin D receptor (VDR) gene polymorphisms and musculoskeletal injury (MI) in elite football players. In total, 54 male professional football players were recruited from an official Italian professional championship team between 2009 and 2013. The cohort was genotyped for the ApaI, BsmI and FokI polymorphisms and MI data were collected over four football seasons. No significant differences were identified among the genotypes in the incidence rates or severity of MI (P=0.254). In addition, no significant associations were observed between VDR polymorphisms and MI phenotypes (P=0.460). However, the results of the casewise multiple regression analysis indicated that the ApaI genotypes accounted for 18% of injury severity (P=0.002). Therefore, while the BsmI and FokI polymorphisms did not appear to be associated with the severity or incidence of MI, the ApaI genotypes may have influenced the severity of muscle injury in top-level football players. PMID:26161149

  15. Rapid gene mapping in Caenorhabditis elegans using a high density polymorphism map.

    PubMed

    Wicks, S R; Yeh, R T; Gish, W R; Waterston, R H; Plasterk, R H

    2001-06-01

    Single nucleotide polymorphisms (SNPs) are valuable genetic markers of human disease. They also comprise the highest potential density marker set available for mapping experimentally derived mutations in model organisms such as Caenorhabditis elegans. To facilitate the positional cloning of mutations we have identified polymorphisms in CB4856, an isolate from a Hawaiian island that shows a uniformly high density of polymorphisms compared with the reference Bristol N2 strain. Based on 5.4 Mbp of aligned sequences, we predicted 6,222 polymorphisms. Furthermore, 3,457 of these markers modify restriction enzyme recognition sites ('snip-SNPs') and are therefore easily detected as RFLPs. Of these, 493 were experimentally confirmed by restriction digest to produce a snip-SNP map of the worm genome. A mapping strategy using snip-SNPs and bulked segregant analysis (BSA) is outlined. CB4856 is crossed into a mutant strain, and exclusion of CB4856 alleles of a subset of snip-SNPs in mutant progeny is assessed with BSA. The proximity of a linked marker to the mutation is estimated by the relative proportion of each form of the biallelic marker in populations of wildtype and mutant genomes. The usefulness of this approach is illustrated by the rapid mapping of the dyf-5 gene. PMID:11381264

  16. Functional polymorphisms in the IL-10 gene with susceptibility to esophageal, nasopharyngeal, and oral cancers.

    PubMed

    Li, Yu-Fen; Yang, Pei-Zhen; Li, Hua-Feng

    2016-03-18

    Emerging evidence showed that functional polymorphisms in the IL-10 gene may have effects on individuals' susceptibility to nasopharyngeal, oral and esophageal cancers, yet individually published findings are inconsistent. We therefore designed the meta-analysis to investigate the correlations of IL-10 genetic polymorphisms with susceptibility to nasopharyngeal, oral and esophageal cancers. The EMBASE, MEDLINE, CINAHL, Web of Science and the Chinese Biomedical Database (CBM) databases were searched with no language restrictions. We use Comprehensive Meta-analysis 2.0 software to carry out statistical analysis. Ten case-control studies with a number of 1,883 patients and 2,857 healthy subjects were enrolled. Our results revealed that IL-10 rs1800872 T>G and rs1800896 A>G polymorphisms has a significantly association with the increased risk of esophageal cancer under the allele and dominant models; rs1800871 T>G, rs1800872 T>G and rs1800896 A>G under allele and dominant models could increase the risk of nasopharyngeal cancer; rs1800871T>G, rs1800872T>G and rs1800896 A>G SNPs under allele model were closely related to the susceptibility to oral cancer. Our findings support the point that IL-10 genetic polymorphisms may play essential role in identifying esophageal cancer, nasopharyngeal cancer and oral cancer at early stage. PMID:27002767

  17. Matrix metalloproteinase gene polymorphisms and periodontitis susceptibility: a meta-analysis involving 6,162 individuals

    PubMed Central

    Weng, Hong; Yan, Yan; Jin, Ying-Hui; Meng, Xiang-Yu; Mo, Yuan-Yuan; Zeng, Xian-Tao

    2016-01-01

    We aimed to systematically investigate the potential association of matrix metalloproteinase (MMP)-9, -3, -2, and -8 gene polymorphisms with susceptibility to periodontitis using meta-analysis. A literature search in PubMed, Embase, and Web of Sciencewas conducted to obtain relevant publications. Finally a total of 16 articles with 24 case-control studies (nine on MMP-9-1562 C/T, seven on MMP-3-1171 A5/A6, four on MMP-2-753C/T, and four on MMP-8-799 C/T) were considered in this meta-analysis. The results based on 2,724 periodontitis patients and 3,438 controls showed that MMP-9-1562C/T, MMP-3-1171 A5/A6, and MMP-8-799C/T polymorphisms were associated with periodontitis susceptibility. No significant association was found between MMP-2-753 C/T and periodontitis susceptibility. Subgroup analyses suggested that the MMP-9-1562 C/T polymorphism reduced chronic periodontitis susceptibility and MMP-3-1171 A5/A6polymorphism increased chronic periodontitis susceptibility. In summary, current evidence demonstrated that MMP-9-753 C/Tpolymorphism reduced the risk of periodontitis, MMP-3-1171 5A/6A and MMP-8-799 C/Tpolymorphisms increased the risk of periodontitis, and MMP-2-753 C/T was not associated with risk of periodontitis. PMID:27095260

  18. hOGG1 gene polymorphisms and susceptibility to polycystic ovary syndrome

    PubMed Central

    XIA, YANJIE; WANG, WENQING; WANG, LEI; SHEN, SHANMEI; CAO, YUNXIA; YI, LONG; GAO, QIAN; WANG, YONG

    2016-01-01

    Oxidative stress generates 8-hydroxy-2′-deoxyguanine (8-oxodG), which can structurally modify DNA. Glycosylase hOGG1 can remove the mutagenic lesion 8-oxodG from DNA. The aim of the present study was to determine whether polymorphisms in hOGG1 were associated with the risk of polycystic ovary syndrome (PCOS). One common single-nucleotide polymorphism (Ser326Cys) in exon 7 and four rare polymorphisms (c.-18G>T, c.-23A>G, c.-45G>A and c. −53G>C) were screened in the 5′ untranslated region of the hOGG1 gene. No such distributional differences were observed between the PCOS patients and controls either in the genotype frequency or in the allele frequency. There were no differences in the clinical variables among the different genotypes in all the variants, except that the follicle-stimulating hormone level was elevated in the GC genotype of c. −53G>C in PCOS patients (P=0.002). These results suggest that the polymorphisms in hOGG1 may not be an independent risk factor for PCOS. PMID:27073625

  19. Limited Polymorphism of the Plasmodium vivax Merozoite Surface Protein 1 Gene in Isolates from Turkey

    PubMed Central

    Zeyrek, Fadile Yildiz; Tachibana, Shin-Ichiro; Yuksel, Fehmi; Doni, Nebiye; Palacpac, Nirianne; Arisue, Nobuko; Horii, Toshihiro; Coban, Cevayir; Tanabe, Kazuyuki

    2010-01-01

    The 200-kD merozoite surface protein of Plasmodium vivax (PvMSP-1) is one of the leading vaccine candidates against P. vivax malaria. However, the gene encoding PvMSP-1 (pvmsp1) is highly polymorphic and is a major obstacle to effective vaccine development. To further understand polymorphism in pvmsp1, we obtained 30 full-length pvmsp1 sequences from southeastern Turkey. Comparative analysis of sequences from Turkey and other areas showed substantially limited polymorphism. Substitutions were found at 280 and 162 amino acid sites in samples from other regions and those from Turkey, respectively. Eight substitutions were unique to Turkey. In one of them, D/E at position 1706 in the C-terminal 19-kD region, the K/E change at 1709 was the only polymorphism previously known. Limited diversity was also observed in microsatellites. Data suggest a recent population bottleneck in Turkey that may have obscured a signature for balancing selection in the C-terminal 42-kD region, which was otherwise detectable in other areas. PMID:21118926

  20. Catechol-O-Methyltransferase Gene Polymorphisms in Specific Obsessive-Compulsive Disorder Patients' Subgroups.

    PubMed

    Melo-Felippe, Fernanda Brito; de Salles Andrade, Juliana Braga; Giori, Isabele Gomes; Vieira-Fonseca, Tamiris; Fontenelle, Leonardo Franklin; Kohlrausch, Fabiana Barzotti

    2016-01-01

    Pharmacological data and animal models support the hypothesis that the dopaminergic (DA) system is implicated in obsessive-compulsive disorder (OCD). Therefore, this case-control study assessed whether genetics variations in catechol-O-methyltransferase gene (COMT) could influence susceptibility to OCD and OCD features in a Brazilian sample. A sample of 199 patients with OCD and 200 healthy individuals was genotyped for -287A > G (rs2075507) and Val158Met (rs4680) single nucleotide polymorphisms (SNPs) by TaqMan(®) or restriction mapping. We observed a statistically significant predominance of the Met low-activity allele in the male patient group as compared to the male healthy control group. The -287A > G polymorphism's genotypes and alleles were significantly overrepresented among male individuals with ordering and female subjects with washing symptoms. We also found female hoarders to exhibit a significant higher frequency of the low activity Met/Met genotype of Val158Met polymorphism compared to female patients who did not express this dimension. Our data suggest an influence of COMT polymorphisms on OCD and OCD patients' features, such as gender, and ordering, washing, and hoarding symptom dimensions. Further studies to confirm the clinical importance of COMT SNPs in OCD are warranted. PMID:26687156

  1. Interleukin-18 gene promoter 607A polymorphism, but not 137C polymorphism, is a protective factor for ischemic stroke in the Chinese population: A meta-analysis.

    PubMed

    Zhang, Ming-Jie; Zhou, Yi; Wang, Xu; Chen, Xue; Pi, Yan; Guo, Lu; Gao, Chang-Yue; Li, Jing-Cheng; Zhang, Li-Li

    2016-09-01

    Some epidemiological studies have evaluated the association between interleukin (IL)-18 promoter polymorphisms and the risk of ischemic stroke (IS), but the results were inconsistent. The present meta-analysis was therefore performed to investigate the relationship between IL-18 promoter 137G/C and 607C/A polymorphisms and the risk of IS in the Chinese population. Related studies from PubMed, Embase, Web of Science, CBMdisc and CNKI databases up to November 1, 2014 were systematically searched, also the reference lists of identified articles were manually searched. Information was extracted to calculate for the allelic, genotypic, dominant and recessive models using the pooled odds ratios (ORs) along with 95% confidence intervals (CIs). Evidence of significant association between 607C/A polymorphism and risk of IS was found in four genetic models based on the overall population. However, no significant association between 137G/C polymorphism and risk of IS was found in four genetic models. In summary, the present study suggests that IL-18 gene promoter 607A polymorphism is a protective factor for IS in the Chinese population, while 137C polymorphism has weaker or no protective properties. Still, a larger number of studies with large scale and sufficient original information are required to further confirm our findings. PMID:27419078

  2. Association of programmed death-1 gene polymorphism rs2227981 with tumor: evidence from a meta analysis

    PubMed Central

    Mamat, Umarjan; Arkinjan, Muyassar

    2015-01-01

    To investigate the association of programmed death-1 gene polymorphism rs2227981 with tumor risk. The PubMed, Medline, Ovid Medline, EMBASE, Web of Knowledge were searched. Meta-analyses were conducted using RevMan 5.2.2 software. Total six researches involving in a total of 1427 tumor patients and 1811 healthy control people were included into this meta analysis. There was no association of PD-1 gene polymorphism with total tumor risk under four genetic models. (CT+TT vs CC, OR=1.09, 95% CI=0.80-1.49, P=0.59; CT+CC vs TT, OR=0.93, 95% CI=0.52-1.66, P=0.61; TT vs CC, OR=0.99, 95% CI=0.57-1.72, P=0.97; CT vs CC, OR=1.16, 95% CI=0.80-1.70, P=0.43). The sub-group analysis shown there were a significantly difference on association of PD-1 gene polymorphism with digestive system tumor risk between tumor patients and healthy control people, except recessive model. (CT+TT vs CC, OR=1.57, 95% CI=1.20-2.07, P=0.001; TT vs CC, OR=1.67, 95% CI=1.12-2.49, P=0.01; CT vs CC, OR=1.51, 95% CI=1.13-2.01, P=0.005). Moreover, the meta analysis results shown that there were association of PD-1 gene polymorphism with tumor risk under two models for the tumor specific occurring only in women. (CT+TT vs CC, OR=0.80, 95% CI=0.67-0.95, P=0.01; TT vs CC, OR=0.61, 95% CI=0.44-0.83, P=0.002). This study suggests that PD-1 gene polymorphism rs2227981 is associated with specific tumor types, including digestive system tumor and tumor specific occurring in woman. PMID:26550254

  3. Association between SNAP-25 gene polymorphisms and cognition in autism: functional consequences and potential therapeutic strategies

    PubMed Central

    Braida, D; Guerini, F R; Ponzoni, L; Corradini, I; De Astis, S; Pattini, L; Bolognesi, E; Benfante, R; Fornasari, D; Chiappedi, M; Ghezzo, A; Clerici, M; Matteoli, M; Sala, M

    2015-01-01

    Synaptosomal-associated protein of 25 kDa (SNAP-25) is involved in different neuropsychiatric disorders, including schizophrenia and attention-deficit/hyperactivity disorder. Consistently, SNAP-25 polymorphisms in humans are associated with hyperactivity and/or with low cognitive scores. We analysed five SNAP-25 gene polymorphisms (rs363050, rs363039, rs363043, rs3746544 and rs1051312) in 46 autistic children trying to correlate them with Childhood Autism Rating Scale and electroencephalogram (EEG) abnormalities. The functional effects of rs363050 single-nucleotide polymorphism (SNP) on the gene transcriptional activity, by means of the luciferase reporter gene, were evaluated. To investigate the functional consequences that SNAP-25 reduction may have in children, the behaviour and EEG of SNAP-25+/− adolescent mice (SNAP-25+/+) were studied. Significant association of SNAP-25 polymorphism with decreasing cognitive scores was observed. Analysis of transcriptional activity revealed that SNP rs363050 encompasses a regulatory element, leading to protein expression decrease. Reduction of SNAP-25 levels in adolescent mice was associated with hyperactivity, cognitive and social impairment and an abnormal EEG, characterized by the occurrence of frequent spikes. Both EEG abnormalities and behavioural deficits were rescued by repeated exposure for 21 days to sodium salt valproate (VLP). A partial recovery of SNAP-25 expression content in SNAP-25+/− hippocampi was also observed by means of western blotting. A reduced expression of SNAP-25 is responsible for the cognitive deficits in children affected by autism spectrum disorders, as presumably occurring in the presence of rs363050(G) allele, and for behavioural and EEG alterations in adolescent mice. VLP treatment could result in novel therapeutic strategies. PMID:25629685

  4. No association between androgen or vitamin D receptor gene polymorphisms and risk of breast cancer.

    PubMed

    Dunning, A M; McBride, S; Gregory, J; Durocher, F; Foster, N A; Healey, C S; Smith, N; Pharoah, P D; Luben, R N; Easton, D F; Ponder, B A

    1999-11-01

    Endogenous hormone exposure is known to alter breast cancer susceptibility and genes responsive to such hormones are plausible candidates for predisposition genes. We have examined polymorphisms in genes for two members of the nuclear receptor superfamily which are expressed in breast tissue and known to moderate rates of cell proliferation in a case-control association study: the androgen receptor (AR) and the vitamin D receptor (VDR). We have used two series of Caucasian female breast cancer cases, one incident and one prevalent, and compared both with two sets of matched controls from the East Anglian region of Britain. Since the results are similar in the two series we have combined them. The AR poly[Gly](n) and poly[Gln](n) tracts were genotyped in a total of 508 female breast cancer cases and 426 controls. The VDR TaqI polymorphism was analysed in 951 cases and 627 controls drawn from the same population series. There were no significant differences between cases and controls for either the AR or VDR polymorphisms. Compared with individuals with two short alleles (<22 repeats) of the AR poly[Gln](n) tract, the odds ratios and 95% confidence intervals (95% CI) for individuals with one or two long alleles were 0.82 (95% CI 0.62-1.09) and 1.31 (95% CI 0.87-1.97), respectively. Heterozygotes and homozygotes for the VDR TaqI cutting site had odds ratios of 1.01 (95% CI 0.81-1.27) and 0.97 (95% CI 0.71-1.32), respectively. None of the AR or VDR polymorphisms investigated has a major effect on risk of breast cancer in the British population. PMID:10545416

  5. Hydroxymethylbilane synthase: Complete genomic sequence and amplifiable polymorphisms in the human gene

    SciTech Connect

    Yoo, Hanwook; Warner, C.A.; Chen, Chiahsiang; Desnick, R.J. )

    1993-01-01

    Acute intermittent porphyria (AIP), an autosomal dominant inborn error of heme biosynthesis, results from the half-normal activity of the heme biosynthetic enzyme hydroxymethylbilane synthase (HMB-synthase). Heterozygous individuals are prone to life-threatening acute neurologic attacks, which are precipitated by certain drugs and other metabolic, hormonal, and nutritional factors. Since the biochemical diagnosis of heterozygous individuals has been problematic, recent efforts have focused on the identification of mutations and diagnostically useful restriction fragment length polymorphisms (RFLPS) in the HMB-synthase gene. To facilitate these endeavors, the human HMB-synthase gene, including 1.1 kb of the 5[prime] flanking region, was isolated and completely sequenced in both orientations. The 10,024-bp gene contained 15 exons ranging in size from 39 to 438 bp and 14 introns ranging from 87 to 2913 bp. All intron/exon boundaries conformed to the GT/AG consensus rule. There were six Alu repetitive elements, one of the J and five of the Sa subfamilies. Analysis of the 1. I -kb 5[prime]flanking region revealed putative regulatory elements for the housekeeping promoter including AP1, AP4, SP1, TRE, ENH, and CAC. This region contained 10 HpaII sites and had an overall GC content of 54%. Three new polymorphic sites were identified by the single-strand conformation polymorphism (SSCP) technique, a common BsmAI site in intron 3 (3581 A/G), a common HinfI RFLP in intron 10 (7064 C/A), and a rare MnlI site in intron 14 (7998G/A). The allele frequencies of five previously known and the new polymorphic sites in a normal Caucasian population indicated that the intron 1 and intron 3 RFLPs were in linkage disequilibrium; however, the Hint I site segregated independently. 54 refs., 6 figs., 3 tabs.

  6. Association of Environmental Arsenic Exposure, Genetic Polymorphisms of Susceptible Genes, and Skin Cancers in Taiwan

    PubMed Central

    Hsu, Ling-I; Wu, Meei-Maan; Wang, Yuan-Hung; Lee, Cheng-Yeh; Yang, Tse-Yen; Hsiao, Bo-Yu; Chen, Chien-Jen

    2015-01-01

    Deficiency in the capability of xenobiotic detoxification and arsenic methylation may be correlated with individual susceptibility to arsenic-related skin cancers. We hypothesized that glutathione S-transferase (GST M1, T1, and P1), reactive oxygen species (ROS) related metabolic genes (NQO1, EPHX1, and HO-1), and DNA repair genes (XRCC1, XPD, hOGG1, and ATM) together may play a role in arsenic-induced skin carcinogenesis. We conducted a case-control study consisting of 70 pathologically confirmed skin cancer patients and 210 age and gender matched participants with genotyping of 12 selected polymorphisms. The skin cancer risks were estimated by odds ratio (OR) and 95% confidence interval (CI) using logistic regression. EPHX1 Tyr113His, XPD C156A, and GSTT1 null genotypes were associated with skin cancer risk (OR = 2.99, 95% CI = 1.01–8.83; OR = 2.04, 95% CI = 0.99–4.27; OR = 1.74, 95% CI = 1.00–3.02, resp.). However, none of these polymorphisms showed significant association after considering arsenic exposure status. Individuals carrying three risk polymorphisms of EPHX1 Tyr113His, XPD C156A, and GSTs presented a 400% increased skin cancer risk when compared to those with less than or equal to one polymorphism. In conclusion, GSTs, EPHX1, and XPD are potential ge