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Sample records for adiponectin gene polymorphism

  1. Adiponectin gene polymorphisms: Association with childhood obesity.

    PubMed

    Fraga, Vanêssa Gomes; Gomes, Karina Braga

    2014-03-01

    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. PMID:27625863

  2. 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. PMID:27625863

  3. Associations of adiponectin gene polymorphisms with polycystic ovary syndrome: a meta-analysis.

    PubMed

    Jia, Hongxia; Yu, Lili; Guo, Xuxiao; Gao, Wei; Jiang, Zhaoshun

    2012-10-01

    Adiponectin gene polymorphisms have been implicated in polycystic ovary syndrome (PCOS) development. However, results from previous studies were inconsistent and inconclusive. To shed some light on the relationship of two adiponectin gene polymorphisms, T45G and G276T, with PCOS, we conducted the current meta-analysis. PubMed was used for searching all eligible studies up to September 30, 2011. Odds ratio (OR) with the corresponding 95% confidence interval (CI) was adopted to evaluate the strength of the associations. In total, ten case-control studies involving 2,821 participants were included in the meta-analysis. Results showed that the T45G polymorphism was not associated with PCOS for allelic contrast (OR = 1.10, 95%CI: 0.83-1.44, P = 0.514), with evidence of large heterogeneity (P(heterogeneity) = 0.002). Concerning G276T polymorphism, the results showed that the T allele was related to a reduced risk of PCOS compared with the G allele under allelic genetic model (OR = 0.81, 95%CI: 0.70-0.93, P = 0.003), and no significant heterogeneity (P(heterogeneity) = 0.268) was revealed. Similar results were observed under additive, dominant and recessive genetic models for both of these two polymorphisms. No publication bias was detected. Our results suggested that the T45G polymorphism of adiponectin gene was not significantly associated with PCOS, while the G276T polymorphism was related to a decreased risk of PCOS.

  4. Adiponectin gene polymorphisms (T45G and G276T), adiponectin levels and risk for metabolic diseases in an Arab population.

    PubMed

    Al-Daghri, Nasser M; Al-Attas, Omar S; Alokail, Majed S; Alkharfy, Khalid M; Hussain, Tajamul; Yakout, Sobhy; Vinodson, Benjamin; Sabico, Shaun

    2012-02-01

    In this study we examined the association of adiponectin gene variants with circulating adiponectin, and known metabolic diseases in 298 healthy controls and 297 Saudi subjects with type 2 diabetes mellitus (T2DM). Anthropometric and biochemical parameters were measured by standard procedures. Genotyping of T45G and G276T single nucleotide polymorphisms of adiponectin gene was carried out by PCR-RFLP analysis. No significant differences in the genotype distribution of T45G and G276T polymorphism were found between control and diabetic subjects. Neither SNP conferred an association with T2DM, obesity, hypertension or dyslipidemia. Despite a marked decrease in patients as opposed to controls, adiponectin levels were not different according to genotypes of T45G and G276T polymorphisms in control and patients. Thus, neither adiponectin SNPs independently conferred increased T2DM risk nor in other metabolic conditions considered such as obesity, hypertension or dyslipidemia. These findings support the existence of population based differences in the association of adiponectin gene variants with metabolic phenotypes and emphasize the importance of studying multiple polymorphisms, sufficient enough to identify the adiponectin gene as a genetic marker for several non-chronic communicable diseases.

  5. Biomarkers of Adiponectin: Plasma Protein Variation and Genomic DNA Polymorphisms

    PubMed Central

    Gu, Harvest F.

    2009-01-01

    Adiponectin is secreted by white adipose tissue and exists as the most abundant adipokine in the human plasma. Recent research has indicated that plasma adiponectin levels are inversely correlated with body mass index (BMI) and insulin resistance. Reduction of plasma adiponectin levels is commonly observed in the patients with type 2 diabetes (T2D) and/or in those who are obese in comparison with healthy control individuals. The adiponectin (AdipoQ) gene has a moderate linkage disequilibrium (LD), but two small LD blocks are observed, respectively, in the promoter region and the boundary of exon 2-intron 2. Genetic association studies have demonstrated that single nucleotide polymorphisms (SNPs) +45G15G(T/G) in exon 2 and +276G/T in intron 2 of the AdipoQ gene confer the risk susceptibility to the development of T2D, obesity and diabetic nephropathy (DN). The SNPs in the promoter region, including −11426A/G, −11377C/G and −11391G/A, are found to be associated with T2D and DN. Recent research has indicated that the promoter polymorphisms interfere with the AdipoQ promoter activity. The haplotypes constructed by the promoter polymorphisms and SNP +276G/T in intron 2 are associated with circulating adiponectin levels. This review summarises genetic and pathophysiological relevancies of adiponectin and discusses about the biomarkers of adiponectin plasma protein variation and genomic DNA polymorphisms. PMID:20029651

  6. 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

  7. 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

  8. Single-nucleotide polymorphisms and haplotypes in the adiponectin gene contribute to the genetic risk for type 2 diabetes in Tunisian Arabs.

    PubMed

    Mtiraoui, Nabil; Ezzidi, Intissar; Turki, Amira; Chaieb, Arbi; Mahjoub, Touhami; Almawi, Wassim Y

    2012-08-01

    Adiponectin is an adipocyte-produced protein involved in regulating glucose, lipid, and energy metabolism, and is encoded by ADIPOQ (APM1) gene. ADIPOQ polymorphisms were previously associated with type 2 diabetes (T2DM) in Caucasian and non-Caucasian populations. We investigated the contribution of 13 polymorphisms in the promoter, coding regions, and 3'untranslated region of ADIPOQ gene to T2DM in 917 patients and 748 normoglycemic control subjects. ADIPOQ genotyping was done by allelic discrimination method. Of the 13 ADIPOQ variants analyzed, higher minor allele frequency of rs16861194 (P<0.001), rs17300539 (P<0.001), rs266729 (P<0.001), rs822396 (P=0.02), rs2241767 (P=0.03), and rs1063538 (P=0.02) were seen in T2DM cases. Varied association of ADIPOQ genotypes with T2DM was seen according to the genetic model used: rs17300539 and rs266729 were significantly associated with T2DM under the three models, while rs16861194 was association with T2DM under additive and dominant models, and rs822396, rs2241766, and rs1063538 were associated with T2DM under the dominant models only. Haploview analysis revealed low linkage disequilibrium between the ADIPOQ variants, resulting in high haplotype diversity, and two blocks were identified, each differentially associated with T2DM. These results support a significant association of ADIPOQ gene polymorphism with T2DM in Tunisian Arabs.

  9. Association of Adiponectin Gene Polymorphisms With the Risk of Coronary Artery Disease in Patients With Nonalcoholic Fatty Liver Disease in a Chinese Han Population

    PubMed Central

    Du, Shui-Xian; Lu, Lin-Lin; Liu, Yang; Dong, Quan-Jiang; Xuan, Shi-Ying; Xin, Yong-Ning

    2016-01-01

    Background Cardiovascular events are an independent risk factor for nonalcoholic fatty liver disease (NAFLD), which is the leading cause of mortality in NAFLD patients. Several recent studies demonstrated that adiponectin (Ad) polymorphisms were involved in the progression of NAFLD and coronary artery disease (CAD). However, reports on the association between Ad polymorphisms and the risk of developing CAD in NAFLD patients are lacking in a Northern Han Chinese population. Objectives The present study was designed to evaluate the association between Ad gene polymorphisms (rs266729 and rs2241766) and the risk of developing CAD in Northern Han Chinese patients with NAFLD. Materials and Methods In this case-control study, using the polymerase chain reaction (PCR), Adrs266729 and rs2241766 gene polymorphisms were genotyped in B-type ultrasonography-proven NAFLD patients, with (n = 246) or without (n = 247) CAD and in healthy controls (n = 304). Serum lipid profiles were determined using biochemical methods. Statistical analyses were performed using SPSS 17.0 statistical software. Results There were significant differences in the Adrs266729 G allele between the NAFLD patients with and without CAD (P < 0.05). In addition, there was a significant difference in the Adrs2241766 G allele of the NAFLD patients compared with that of the controls (P < 0.05). In the NAFLD CAD population, carriers of the G allele of Adrs266729 had higher serum triglycerides (TG), total cholesterol (TC), fasting plasma glucose (FPG), and low-density lipoprotein (LDL) levels and a lower Ad level than their noncarrier counterparts (P = 0.031, P = 0.034, P = 0.007, P < 0.001, and P < 0.001, respectively). NAFLD patients without CAD had higher TG and serum FPG values and a lower Ad level than their noncarrier counterparts (P = 0.014, P = 0.038, and P < 0.001, respectively). In the NAFLD patients with/without CAD, the carriers of the G allele of Adrs2241766 had higher TG levels (P = 0.039 and P = 0

  10. Oxidized low-density lipoprotein and lipoprotein(a) levels in chronic kidney disease patients under hemodialysis: influence of adiponectin and of a polymorphism in the apolipoprotein(a) gene.

    PubMed

    Ribeiro, Sandra; Faria, Maria do Sameiro; Silva, Gil; Nascimento, Henrique; Rocha-Pereira, Petronila; Miranda, Vasco; Vieira, Emília; Santos, Rosário; Mendonça, Denisa; Quintanilha, Alexandre; Costa, Elísio; Belo, Luís; Santos-Silva, Alice

    2012-10-01

    Chronic kidney disease (CKD) has been associated with an abnormal lipid profile. Our aim was to study the interplay between oxidized low-density lipoprotein (ox-LDL), adiponectin, and blood lipids and lipoproteins in Portuguese patients with CKD under hemodialysis (HD); the influence of the pentanucleotide repeat polymorphism in the apolipoprotein(a) (apo [a]) gene upon lipoprotein(a) (Lp[a]) levels in these patients. We studied 187 HD patients and 25 healthy individuals. ox-LDL and adiponectin were measured using enzyme-linked immunoassays. Apo(a) genotyping was performed by polymerase chain reaction, followed by electrophoresis in polyacrylamide gel. Compared with controls, patients presented with significantly higher levels of adiponectin, Lp(a), and ox-LDL/low-density lipoprotein cholesterol (LDLc) ratio; significantly lower levels of total cholesterol (TC), LDLc, apo A-I, apo B, ox-LDL, and TC/high-density lipoprotein cholesterol (HDLc) ratio were also observed. Similar changes were observed for patients with or without statin therapy, as compared with controls, except for Lp(a). Multiple linear regression analysis showed that body mass index, HDLc, time on HD, and triglycerides (TG) were independent determinants of adiponectin levels, and that apo B, TG and LDLc were independent determinants of ox-LDL concentration. Concerning the apo(a) genotype, the homozygous (TTTTA)8/8 repeats was the most prevalent (50.8%). A raised proportion of LDL particles that are oxidized was observed. Adiponectin almost doubled its values in patients and seems to be an important determinant in HDLc and TG levels, improving the lipid profile in these patients. Apo(a) alleles with a lower number of repetitions are more frequent in patients with higher Lp(a).

  11. 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

  12. Common variants in genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1/2), adiponectin concentrations, and diabetes incidence in the Diabetes Prevention Program

    PubMed Central

    Mather, K. J.; Christophi, C. A.; Jablonski, K. A.; Knowler, W. C.; Goldberg, R. B.; Kahn, S. E.; Spector, T.; Dastani, Z.; Waterworth, D.; Richards, J. B.; Funahashi, T.; Pi-Sunyer, F. X.; Pollin, T. I.; Florez, J. C.; Franks, P. W.

    2012-01-01

    Aims Baseline adiponectin concentrations predict incident Type 2 diabetes mellitus in the Diabetes Prevention Program. We tested the hypothesis that common variants in the genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1, ADIPOR2) would associate with circulating adiponectin concentrations and/or with diabetes incidence in the Diabetes Prevention Program population. Methods Seventy-seven tagging single-nucleotide polymorphisms (SNPs) in ADIPOQ (24), ADIPOR1 (22) and ADIPOR2 (31) were genotyped. Associations of SNPs with baseline adiponectin concentrations were evaluated using linear modelling. Associations of SNPs with diabetes incidence were evaluated using Cox proportional hazards modelling. Results Thirteen of 24 ADIPOQ SNPs were significantly associated with baseline adiponectin concentrations. Multivariable analysis including these 13 SNPs revealed strong independent contributions from rs17366568, rs1648707, rs17373414 and rs1403696 with adiponectin concentrations. However, no ADIPOQ SNPs were directly associated with diabetes incidence. Two ADIPOR1 SNPs (rs1342387 and rs12733285) were associated with ~18% increased diabetes incidence for carriers of the minor allele without differences across treatment groups, and without any relationship with adiponectin concentrations. Conclusions ADIPOQ SNPs are significantly associated with adiponectin concentrations in the Diabetes Prevention Program cohort. This observation extends prior observations from unselected populations of European descent into a broader multi-ethnic population, and confirms the relevance of these variants in an obese/dysglycaemic population. Despite the robust relationship between adiponectin concentrations and diabetes risk in this cohort, variants in ADIPOQ that relate to adiponectin concentrations do not relate to diabetes risk in this population. ADIPOR1 variants exerted significant effects on diabetes risk distinct from any effect of adiponectin concentrations. [Clinical

  13. ADIPOQ, ADIPOR1, and ADIPOR2 Polymorphisms in Relation to Serum Adiponectin Levels and Body Mass Index in Black and White Women

    PubMed Central

    Cohen, Sarah S.; Gammon, Marilie D.; North, Kari E.; Millikan, Robert C.; Lange, Ethan M.; Williams, Scott M.; Zheng, Wei; Cai, Qiuyin; Long, Jirong; Smith, Jeffrey R.; Signorello, Lisa B.; Blot, William J.; Matthews, Charles E.

    2012-01-01

    Adiponectin is an adipose-secreted protein with influence on several physiologic pathways including those related to insulin sensitivity, inflammation, and atherogenesis. Adiponectin levels are highly heritable and several single nucleotide polymorphisms (SNPs) in adiponectin-related genes (ADIPOQ, ADIPOR1, ADIPOR2) have been examined in relation to circulating adiponectin levels and obesity phenotypes, but despite differences in adiponectin levels and obesity prevalence by race, few studies have included black participants. Using cross-sectional interview data and blood samples collected from 990 black and 977 white women enrolled in the Southern Community Cohort Study from 2002 to 2006, we examined 25 SNPs in ADIPOQ, 19 in ADIPOR1, and 27 in ADIPOR2 in relation to serum adiponectin levels and body mass index (BMI) using race-stratified linear regression models adjusted for age and percentage African ancestry. SNP rs17366568 in ADIPOQ was significantly associated with serum adiponectin levels in white women only (adjusted mean adiponectin levels = 15.9 for G/G genotype, 13.7 for A/G, and 9.3 for A/A, p=0.00036). No other SNPs were associated with adiponectin or BMI among blacks or whites. Because adiponectin levels as well as obesity are highly heritable and vary by race but associations with polymorphisms in the ADIPOQ, ADIPOR1, and ADIPOR2 genes have been few in this and other studies, future work including large populations from diverse racial groups is needed to detect additional genetic variants that influence adiponectin and BMI. PMID:21273992

  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. 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

  17. 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.

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

    PubMed

    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. Influence of the interaction between the adiponectin G276T polymorphism and body mass index on lipid levels in healthy children.

    PubMed

    Riestra, Pía; García-Anguita, Alicia; Lasunción, Miguel A; Mangas, Alipio; de Oya, Manuel; Garcés, Carmen

    2012-04-01

    Adiponectin is an adipose tissue-specific hormone which is inversely associated with metabolic alterations related to atherosclerosis. Polymorphisms in the adiponectin gene (AdipoQ) have been related to low adiponectin levels as well as several cardiovascular risk factors, but this association remains controversial. In our study we investigated the relationship between the AdipoQ T45G (rs: 2241766) and G276T (rs: 1501299) polymorphisms and adiponectin concentrations, blood pressure, and lipid and insulin levels, in a population-based sample of 12- to 16-year-old children. The study included 815 healthy Spanish children (388 boys and 427 girls). Plasma glucose and lipid levels were determined by standard methods. Insulin concentrations were measured by RIA, and serum adiponectin levels were determined by ELISA. The AdipoQ T45G and AdipoQ G276T polymorphisms were determined by TaqMan(®) allelic discrimination assays. ANOVA or t test allowed for comparison of the studied parameters across genotypes or genotype groups, respectively. A linear regression analysis was performed to examine the independent relationships of the lipid variables with BMI (body mass index), AdipoQ G276T polymorphism and the interaction between the two. When independently comparing the effect of these polymorphisms in normal-weight and overweight children, we observed that overweight boys carriers of the minor allele T had significantly lower TC, LDL-C and apo A-I levels than non-carriers, but these differences were not apparent in normal-weight boys. Furthermore, linear regression analysis demonstrated that interaction between the BMI and the AdipoQ G276T polymorphism is a significant factor explaining the variations of TC and LDL-C levels. To our knowledge, this is the first study to report an association between the AdipoQ G276T polymorphism and lipid levels in overweight boys alone, thereby suggesting that the influence of the AdipoQ polymorphisms on cardiovascular risk factors may be

  20. Adiponectin and Adiponectin Receptor Gene Variants in Relation to Type 2 Diabetes and Insulin Resistance-Related Phenotypes

    PubMed Central

    Potapov, Viktor A.; Chistiakov, Dimitry A.; Dubinina, Anna; Shamkhalova, Minara S.; Shestakova, Marina V.; Nosikov, Valery V.

    2008-01-01

    BACKGROUND: Alterations in adiponectin-mediated pathways are known to be associated with glucose intolerance, insulin resistance (IR), obesity, and type 2 diabetes (T2D) mellitus. Genetic variations in adiponectin (ADIPOQ) and adiponectin 1 and 2 receptor (ADIPOR1 and ADIPOR2) could have effects on IR-related phenotypes and T2D. Here we examine whether the polymorphic markers rs2241766 (ADIPOQ), rs22753738 (ADIPOR1), rs11061971 and rs16928751 (both in ADIPOR2) are implicated in susceptibility to T2D in a Russian population. METHODS: The polymorphic markers were genotyped in 129 T2D patients, and 117 non-diabetic controls, by polymerase chain reaction (PCR) restriction fragment length polymorphism approach. In the subjects, biochemical characteristics including serum insulin, plasma glucose and serum lipids/lipoproteins were measured and compared for correlation with the genetic variations studied. RESULTS: Allele T of rs11061971 and allele A of rs16928751 showed association with higher risk of diabetes providing odds ratios (OR) of 2.05 (p = 0.0025) and 1.88 (p = 0.018), respectively. Haplotype A-G consisting of allele A of rs11061971 and allele G of rs16928751 was associated with reduced risk of T2D (OR = 0.59, pc = 0.0224). Compared to other variants, diabetic patients double homozygous for A/A of rs16928751 and G/G of rs16928751 had decreased homeostasis model assessment-insulin resistance (pc = 0.0375) and serum triglycerides (pc = 0.0285). CONCLUSIONS: The variants of ADIPOR2 confer susceptibility to T2D and are associated with some IR-related phenotypes in the Russian study population. PMID:18548168

  1. 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

  2. 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

  3. 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}.

  4. Amerindians show association to obesity with adiponectin gene SNP45 and SNP276: population genetics of a food intake control and "thrifty" gene.

    PubMed

    Arnaiz-Villena, Antonio; Fernández-Honrado, Mercedes; Rey, Diego; Enríquez-de-Salamanca, Mercedes; Abd-El-Fatah-Khalil, Sedeka; Arribas, Ignacio; Coca, Carmen; Algora, Manuel; Areces, Cristina

    2013-02-01

    Adiponectin gene polymorphisms SNP45 and SNP276 have been related to metabolic syndrome (MS) and related pathologies, including obesity. However results of associations are contradictory depending on which population is studied. In the present study, these adiponectin SNPs are for the first time studied in Amerindians. Allele frequencies are obtained and comparison with obesity and other MS related parameters are performed. Amerindians were also defined by characteristic HLA genes. Our main results are: (1) SNP276 T is associated to low diastolic blood pressure in Amerindians, (2) SNP45 G allele is correlated with obesity in female but not in male Amerindians, (3) SNP45/SNP276 T/G haplotype in total obese/non-obese subjects tends to show a linkage with non-obese Amerindians, (4) SNP45/SNP276 T/T haplotype is linked to obese Amerindian males. Also, a world population study is carried out finding that SNP45 T and SNP276 T alleles are the most frequent in African Blacks and are found significantly in lower frequencies in Europeans and Asians. This together with the fact that there is a linkage of this haplotype to obese Amerindian males suggest that evolutionary forces related to famine (or population density in relation with available food) may have shaped world population adiponectin polymorphism frequencies. PMID:23108996

  5. Adiponectin regulates expression of hepatic genes critical for glucose and lipid metabolism.

    PubMed

    Liu, Qingqing; Yuan, Bingbing; Lo, Kinyui Alice; Patterson, Heide Christine; Sun, Yutong; Lodish, Harvey F

    2012-09-01

    The effects of adiponectin on hepatic glucose and lipid metabolism at transcriptional level are largely unknown. We profiled hepatic gene expression in adiponectin knockout (KO) and wild-type (WT) mice by RNA sequencing. Compared with WT mice, adiponectin KO mice fed a chow diet exhibited decreased mRNA expression of rate-limiting enzymes in several important glucose and lipid metabolic pathways, including glycolysis, tricarboxylic acid cycle, fatty-acid activation and synthesis, triglyceride synthesis, and cholesterol synthesis. In addition, binding of the transcription factor Hnf4a to DNAs encoding several key metabolic enzymes was reduced in KO mice, suggesting that adiponectin might regulate hepatic gene expression via Hnf4a. Phenotypically, adiponectin KO mice possessed smaller epididymal fat pads and showed reduced body weight compared with WT mice. When fed a high-fat diet, adiponectin KO mice showed significantly reduced lipid accumulation in the liver. These lipogenic defects are consistent with the down-regulation of lipogenic genes in the KO mice.

  6. Gene Polymorphisms in Chronic Periodontitis

    PubMed Central

    Laine, Marja L.; Loos, Bruno G.; Crielaard, W.

    2010-01-01

    We aimed to conduct a review of the literature for gene polymorphisms associated with chronic periodontitis (CP) susceptibility. A comprehensive search of the literature in English was performed using the keywords: periodontitis, periodontal disease, combined with the words genes, mutation, or polymorphism. Candidate gene polymorphism studies with a case-control design and reported genotype frequencies in CP patients were searched and reviewed. There is growing evidence that polymorphisms in the IL1, IL6, IL10, vitamin D receptor, and CD14 genes may be associated with CP in certain populations. However, carriage rates of the rare (R)-allele of any polymorphism varied considerably among studies and most of the studies appeared under-powered and did not correct for other risk factors. Larger cohorts, well-defined phenotypes, control for other risk factors, and analysis of multiple genes and polymorphisms within the same pathway are needed to get a more comprehensive insight into the contribution of gene polymorphisms in CP. PMID:20339487

  7. Adiponectin Gene Variants Are Associated with Insulin Sensitivity in Response to Dietary Fat Consumption in Caucasian Men2

    PubMed Central

    Pérez-Martínez, Pablo; López-Miranda, José; Cruz-Teno, Cristina; Delgado-Lista, Javier; Jiménez-Gómez, Yolanda; Fernández, Juan Marcelo; Gómez, Maria José; Marín, Carmen; Pérez-Jiménez, Francisco; Ordovás, José María

    2008-01-01

    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 (-11391 G > A, 11377 C > G, 45 T > G, and 276 G > T) influences the insulin sensitivity to dietary fat. Healthy volunteers (30 men and 29 women) consumed 3 diets for 4 wk each: an initial period during which all subjects consumed a SFA-rich diet (38% total fat, 20% SFA), followed by a carbohydrate-rich diet (CHO) (30% total fat, 55% carbohydrate) or a monounsaturated fatty acid (MUFA)-rich diet (38% total fat, 22% MUFA) following a randomized, crossover design. After participants consumed each diet, we tested peripheral insulin sensitivity with the insulin suppression test and measured plasma adiponectin concentrations. C/C homozygous men for the -11377 C > G single nucleotide polymorphism (SNP) had a significantly greater decrease in the steady-state plasma glucose concentrations when changing from the SFA-rich (8.95 ± 0.6 mmol/L) to the MUFA-rich (6.04 ± 0.31 mmol/L) and CHO-rich (6.35 ± 0.38 mmol/L) diets than did those carrying the minor G allele (SFA, 6.65 ± 0.4 mmol/L; MUFA, 6.45 ± 0.4 mmol/L; CHO, 5.83 ± 0.3 mmol/L) (P sex × gene × diet interaction = 0.016). These differences did not occur in female participants. Furthermore, C/C men had lower plasma adiponectin concentrations than did C/C women (P sex × gene interaction = 0.015), independently of the dietary fat consumed. None of the variables examined were significantly associated with -11426 A > G, 45T > G, or 276 G > T SNP. In conclusion, C/C homozygous men for the -11377 C > G SNP at adipoQ gene were significantly less insulin resistant after consumption of the MUFA- and CHO-rich diets compared with the SFA-rich diet. This information should help in the identification of vulnerable populations or persons who will benefit from more personalized and mechanism-based dietary recommendations. PMID

  8. 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

  9. 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

  10. Interleukin gene polymorphisms in pneumoconiosis.

    PubMed

    Helmig, Simone; Grossmann, Martin; Wübbeling, Jelena; Schneider, Joachim

    2012-08-01

    Inhaled asbestos fibres are known to cause inflammation processes with the result of lung or pleural fibrosis and malignancies. Interleukins (IL), such as IL-1β, IL-6 and IL-10, have various functions in the regulation of the inflammatory response and in proliferative processes after inhalation of silica dust and can, therefore, influence the pathogenesis of asbestos-induced fibrosis and carcinogenesis. Polymorphisms within these genes may be associated with susceptibility to silica and asbestos-induced lung diseases. Thus, IL-1β, IL-6 and IL-10 polymorphisms were examined to determine an association with asbestos or silica-induced fibrosis or malignancies. Association studies were performed in 1180 individuals, using control subjects (n=177), fibrosis patients (n=605), lung cancer (LC) patients (n=364) and malignant mesothelioma (MM) patients (n=34). IL-1β (C-511T; C+3954T), IL-6 (G-174C) as well as IL-10 (G-1082A) polymorphisms were investigated. Compared to a healthy (control) group, a higher risk was seen for malignant mesothelioma patients in all investigated polymorphisms. The IL-6 -174C allele showed a tendency towards a higher risk for fibrosis or asbestos-induced lung cancer (ORasbestosis, 1.338; 95% CI, 0.71-2.53; ORsilicosis, 1.226; 95% CI, 0.54-2.81; ORfibrosis other aetiology, 1.313; 95% CI, 0.58-2.98 and ORLC asbestos, 2.112; 95% CI, 0.75-5.92). The IL-10 -1082A carrier seemed to be at higher risk for silicosis (ORsilicosis, 2.064; 95% CI, 0.78-5.49) but not for asbestosis. In summary, this study did not reveal sufficient evidence for a significant association of the investigated interleukin polymorphisms with asbestos or silica-induced diseases in the population studied.

  11. [SNPs detection of adiponectin gene and its relationship with carcass and meat quality traits in Qinchuan cattle].

    PubMed

    Yang, Yan-Jie

    2009-10-01

    Four hundred and five Qinchuan cattle at the age of 24 months were used to detect SNPs of adiponectin gene by PCR-SSCP and sequencing technology and to analyze the correlation of SNPs with carcass and meat quality traits using the general linear model (GLM) in SPSS program. Five genotypes (AA, AB, BB, CC, CD) were detected,with one G-->C mutation at 64 bp in exon2 of adiponectin in ABBB genotypes and one C-->T mutation at 50 bp in exon3 of adiponectin in CD genotype. G-->C mutation resulted glutamic acid (GGA) into glutamine (GCA) and C-->T mutation resulted serine (TCA) into leucine (TTA). Statistical analysis revealed that Qinchuan cattle with AA genotype was higher than BB genotype in slaughter weight, back fat thickness, carcass weight, loin muscle area (P < 0.05). The crural girth of AA genotype was significantly higher than AB and BB genotypes (P < 0.01). Qinchuan cattle with CD genotype was higher than CC genotype in slaughter weight, subcutaneous fat thickness, back fat thickness, crural girth, and tenderness (P < 0.05). Adiponectin gene was proved to be closely related to carcass and meat quality traits (P < 0.05), which can be used as a candidate molecular marker for production of high-grade meat in Qinchuan beef cattle.

  12. 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.

  13. [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.

  14. Polymorphisms in Endothelin System Genes, Arsenic Levels and Obesity Risk

    PubMed Central

    Martínez-Barquero, Vanesa; de Marco, Griselda; Martínez-Hervas, Sergio; Rentero, Pilar; Galan-Chilet, Inmaculada; Blesa, Sebastian; Morchon, David; Morcillo, Sonsoles; Rojo, Gemma; Ascaso, Juan Francisco; Real, José Tomás; Martín-Escudero, Juan Carlos; Chaves, Felipe Javier

    2015-01-01

    Background/Objectives Obesity has been linked to morbidity and mortality through increased risk for many chronic diseases. Endothelin (EDN) system has been related to endothelial function but it can be involved in lipid metabolism regulation: Receptor type A (EDNRA) activates lipolysis in adipocytes, the two endothelin receptors mediate arsenic-stimulated adipocyte dysfunction, and endothelin system can regulate adiposity by modulating adiponectin activity in different situations and, therefore, influence obesity development. The aim of the present study was to analyze if single nucleotide polymorphisms (SNPs) in the EDN system could be associated with human obesity. Subjects/Methods We analyzed two samples of general-population-based studies from two different regions of Spain: the VALCAR Study, 468 subjects from the area of Valencia, and the Hortega Study, 1502 subjects from the area of Valladolid. Eighteen SNPs throughout five genes were analyzed using SNPlex. Results We found associations for two polymorphisms of the EDNRB gene which codifies for EDN receptor type B. Genotypes AG and AA of the rs5351 were associated with a lower risk for obesity in the VALCAR sample (p=0.048, OR=0.63) and in the Hortega sample (p=0.001, OR=0.62). Moreover, in the rs3759475 polymorphism, genotypes CT and TT were also associated with lower risk for obesity in the Hortega sample (p=0.0037, OR=0.66) and in the VALCAR sample we found the same tendency (p=0.12, OR=0.70). Furthermore, upon studying the pooled population, we found a stronger association with obesity (p=0.0001, OR=0.61 and p=0.0008, OR=0.66 for rs5351 and rs3759475, respectively). Regarding plasma arsenic levels, we have found a positive association for the two SNPs studied with obesity risk in individuals with higher arsenic levels in plasma: rs5351 (p=0.0054, OR=0.51) and rs3759475 (p=0.009, OR=0.53) Conclusions Our results support the hypothesis that polymorphisms of the EDNRB gene may influence the susceptibility to

  15. Effects of different fatty acids and dietary lipids on adiponectin gene expression in 3T3-L1 cells and C57BL/6J mice adipose tissue.

    PubMed

    Bueno, Allain Amador; Oyama, Lila Missae; de Oliveira, Cristiane; Pisani, Luciana Pelegrini; Ribeiro, Eliane Beraldi; Silveira, Vera Lucia Flor; Oller do Nascimento, Cláudia Maria

    2008-01-01

    Obesity is positively correlated to dietary lipid intake, and the type of lipid may play a causal role in the development of obesity-related pathologies. A major protein secreted by adipose tissue is adiponectin, which has antiatherogenic and antidiabetic properties. The aim of this study was to evaluate the effects of four different high-fat diets (enriched with soybean oil, fish oil, coconut oil, or lard) on adiponectin gene expression and secretion by the white adipose tissue (WAT) of mice fed on a selected diet for either 2 (acute treatment) or 60 days (chronic treatment). Additionally, 3T3-L1 adipocytes were treated for 48 h with six different fatty acids: palmitic, linoleic, eicosapentaenoic (EPA), docosahexaenoic (DHA), lauric, or oleic acid. Serum adiponectin concentration was reduced in the soybean-, coconut-, and lard-enriched diets in both groups. Adiponectin gene expression was lower in retroperitoneal WAT after acute treatment with all diets. The same reduction in levels of adiponectin gene expression was observed in epididymal adipose tissue of animals chronically fed soybean and coconut diets and in 3T3-L1 cells treated with palmitic, linoleic, EPA, and DHA acids. These results indicate that the intake of certain fatty acids may affect serum adiponectin levels in mice and adiponectin gene expression in mouse WAT and 3T3-L1 adipocytes. The effects appear to be time dependent and depot specific. It is postulated that the downregulation of adiponectin expression by dietary enrichment with soybean oil or coconut oil may contribute to the development of insulin resistance and atherosclerosis.

  16. 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.

  17. TNF-α gene polymorphisms and expression.

    PubMed

    El-Tahan, Radwa R; Ghoneim, Ahmed M; El-Mashad, Noha

    2016-01-01

    Tumor necrosis factor alpha (TNF-α) is a proinflammatory cytokine with an important role in the pathogenesis of several diseases. Its encoding gene is located in the short arm of chromosome 6 in the major histocompatibility complex class III region. Most of the TNF-α gene polymorphisms are located in its promoter region and they are thought to affect the susceptibility and/or severity of different human diseases. This review summarizes the data related to the association between TNF-α gene and its receptor polymorphisms, and the development of autoimmune diseases. Among these polymorphisms the -308G/A TNF-α promotor polymorphism has been associated several times with the the development of autoimmune diseases, however some discrepant results have been recorded. The other TNF-α gene polymorphisms had little or no association with autoimmune diseases. Current results about the molecules controlling TNF-α expression are also presented. The discrepancy between different records could be related partly to either the differences in the ethnic origin or number of the studied individuals, or the abundance and activation of other molecules that interact with the TNF-α promotor region or other elements. PMID:27652081

  18. 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.

  19. 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

  20. Adiponectin effects and gene expression in rainbow trout: an in vivo and in vitro approach.

    PubMed

    Sánchez-Gurmaches, Juan; Cruz-Garcia, Lourdes; Gutiérrez, Joaquím; Navarro, Isabel

    2012-04-15

    Here we present the presence of adiponectin and adiponectin receptors [type 1 (adipoR1) and type 2 (adipoR2)] in rainbow trout (Oncorhynchus mykiss) tissues and cell cultures together with the response to different scenarios. In response to fasting, adiponectin expression was up-regulated in adipose tissue, while the expression of its receptors increased in white and red muscle. Insulin injection decreased adipoR1 expression in white and red muscles. We deduce that the adipoRs in trout muscle show opposite responses to increasing insulin plasma levels, which may maintain sensitivity to insulin in this tissue. Adiponectin expression was inhibited by the inflammatory effect of lipopolysaccharide (LPS) in adipose tissue and red muscle. Moreover, results indicate that LPS may lead to mobilization of fat reserves, increasing adipoR1 expression in adipose tissue. The effects of LPS could be mediated through tumour necrosis factor α (TNFα), at least in red muscle. Insulin, growth hormone and TNFα all diminished expression of adipoR2 in adipocytes and adipoR1 in myotubes, while insulin increased the expression of adipoR2 in the muscle cells. Adiponectin activates Akt in rainbow trout myotubes, which may lead to an increase in fatty acid uptake and oxidation. Overall, our results show that the adiponectin system responds differently to various physiological challenges and that it is hormonally controlled in vivo and in vitro. To the best of our knowledge, this is the first time this has been demonstrated in teleosts, and it may be a valuable contribution to our understanding of adipokines in fish.

  1. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome

    PubMed Central

    Kadowaki, Takashi; Yamauchi, Toshimasa; Kubota, Naoto; Hara, Kazuo; Ueki, Kohjiro; Tobe, Kazuyuki

    2006-01-01

    Adiponectin is an adipokine that is specifically and abundantly expressed in adipose tissue and directly sensitizes the body to insulin. Hypoadiponectinemia, caused by interactions of genetic factors such as SNPs in the Adiponectin gene and environmental factors causing obesity, appears to play an important causal role in insulin resistance, type 2 diabetes, and the metabolic syndrome, which are linked to obesity. The adiponectin receptors, AdipoR1 and AdipoR2, which mediate the antidiabetic metabolic actions of adiponectin, have been cloned and are downregulated in obesity-linked insulin resistance. Upregulation of adiponectin is a partial cause of the insulin-sensitizing and antidiabetic actions of thiazolidinediones. Therefore, adiponectin and adiponectin receptors represent potential versatile therapeutic targets to combat obesity-linked diseases characterized by insulin resistance. This Review describes the pathophysiology of adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. PMID:16823476

  2. 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

  3. [Protamine gene polymorphisms and male infertility].

    PubMed

    Jiang, Wei-jun; Zhang, Jing; Xia, Xin-yi; Xu, Hao-qin

    2015-12-01

    Protamine (PRM) is one of the most abundant arginine-rich nucleoproteins in sperm and plays an important role in spermatogenesis. In the late stage of spermatogenesis, the replacement of PRM by histone prompts the closer combination between the nuclear matrix of sperm and nucleoprotein in order for high enrichment and condensation of nuclear chromatin in addition to preventing the sperm genome from mutation induced by internal and external factors. With the development of DNA sequencing techniques, researches on the association between PRM polymorphisms and male fertility are surfacing as a hot field. Many studies show that rs2301365 polymorphism is a risk factor for male infertility and increases the risk of male infertility by 27 - 66%, that rs737008 polymorphism of PRM1 and rs1646022 polymorphism of PRM2 are protective factors against Asian infertility, and that the ratio of PRM1 to PRM2 is intensively associated with male infertility. This review presents an update on the association between PRM gene polymorphisms and male infertility.

  4. 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

  5. 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

  6. 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

  7. Androgen receptor gene polymorphism in zebra species.

    PubMed

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

    2015-09-01

    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

  8. Effects of genetic variants in the promoter region of the bovine adiponectin (ADIPOQ) gene on marbling of Hanwoo beef cattle.

    PubMed

    Choi, Yoonjeong; Davis, Michael E; Chung, Hoyoung

    2015-07-01

    This study aimed to verify genetic effects of the bovine adiponectin (ADIPOQ) gene on carcass traits of Hanwoo cattle. The measured carcass traits were marbling score (MAR), backfat thickness (BFT), loineye area (LEA), and carcass weight (CAW). Selection of primers was based on the bovine ADIPOQ sequence, and the analysis amplified approximately 267 and 333 bp genomic segments, including 67 bp of insertions in the promoter region. Sequencing analysis confirmed genetic variants (g.81966235C>T, g.81966377T>C, and g.81966364D>I) that showed significant effects on MAR. The present results suggest that the identified SNPs are useful genetic markers for the improvement of carcass traits in Hanwoo cattle.

  9. 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.

  10. Roles of leptin, adiponectin and resistin in the transcriptional regulation of steroidogenic genes contributing to decreased Leydig cells function in obesity.

    PubMed

    Roumaud, Pauline; Martin, Luc J

    2015-10-01

    The increase in obesity rate is a major public health issue associated with increased pathological conditions such as type 2 diabetes or cardiovascular diseases. Obesity also contributes to decreased testosterone levels in men. Indeed, the adipose tissue is an endocrine organ which produces hormones such as leptin, adiponectin and resistin. Obesity results in pathological accumulations of leptin and resistin, whereas adiponectin plasma levels are markedly reduced, all having a negative impact on testosterone synthesis. This review focuses on current knowledge related to transcriptional regulation of Leydig cells' steroidogenesis by leptin, adiponectin and resistin. We show that there are crosstalks between the regulatory mechanisms of these hormones and androgen production which may result in a dramatic negative influence on testosterone plasma levels. Indeed leptin, adiponectin and resistin can impact expression of different steroidogenic genes such as Star, Cyp11a1 or Sf1. Further investigations will be required to better define the implications of adipose derived hormones on regulation of steroidogenic genes expression within Leydig cells under physiological as well as pathological conditions.

  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 relationship between BDNF gene polymorphisms and alcoholics in Japan].

    PubMed

    Narita, Shin; Nagahori, Kenta; Yoshihara, Eiji; Nishizawa, Daisuke; Ikeda, Kazutaka; Kawai, Atsuko; Iwahashi, Kazuhiko

    2013-12-01

    As a help of the mechanism elucidation of alcoholism, we studied the relationship between brain-derived neurotrophic factor (BDNF) rs6265, 270 C/T (ID number has not yet been determined), and rs10835210 gene polymorphisms, which are reported to be related to bipolar disorder, and alcoholics. We genotyped the three polymorphisms in the BDNF gene using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) in 65 alcoholics and 71 healthy controls. In this study, there was no significant difference in the frequency of rs6265 and 270 C/T polymorphisms between alcoholics and controls (P > 0.05). However, there was a significant difference in the genotype frequency of rs10835210 polymorphism between alcoholics and controls (P < 0.05), in which the CA heterozygote genotype and A allele frequency was higher in alcoholics than in the controls. It suggests the possibility that the BDNF rs10835210 gene polymorphism affects the etiology of alcoholism.

  13. 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

  14. Genetic polymorphisms in adipokine genes and the risk of obesity: a systematic review and meta-analysis.

    PubMed

    Yu, Zhangbin; Han, Shuping; Cao, Xingguo; Zhu, Chun; Wang, Xuejie; Guo, Xirong

    2012-02-01

    Polymorphisms in adipokine genes, such as leptin (LEP), leptin receptor (LEPR), resistin (RETN), adiponectin (ADIPOQ), interleukin-1β (IL-1β), IL-6 (IL-6), and tumor necrosis factor-α (TNF-α) may be involved in the development of obesity. We conducted a systematic review of published evidence on the association between different adipokine genes and the risk of obesity. Librarian-designed searches of PubMed and HuGeNet, review of reference lists from published reviews and content expert advice identified potentially eligible studies. The genotyping information and polymorphisms of different adipokine genes, numbers of genotyped cases and controls and frequencies of genotypes were extracted from 48 eligible studies included in this review. Twenty-one polymorphisms each associated with obesity in at least one study were identified. Polymorphisms in the adipokine genes, LEP, LEPR, and RETN were not associated with obesity susceptibility, whereas ADIPOQ G276T (T vs. G: odds ratio (OR), 1.59; 95% confidence interval (CI), 1.39-1.81), IL-1β C3953T (CC vs. CT+TT: OR, 1.61; 95% CI, 1.18-2.20), and TNF-α G308A (GG vs. GA+AA: OR, 1.19; 95% CI, 1.02-1.39) polymorphisms were associated with an increased risk of obesity. The IL-6 G174C polymorphism was also associated obesity when using allelic comparisons, the recessive genetic model and the dominant genetic model with OR (95% CI) of 1.95 (1.37-2.77), 1.44 (1.15-1.80), and 1.36 (1.16-1.59), respectively. No significant evidence of publication bias was present. However, these "null" results were underpowered due to a small pooled sample size, and analysis of additional case-control studies with larger sample sizes should provide further clarifications.

  15. 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

  16. 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.

  17. 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…

  18. Isolation of tetranucleotide repeat polymorphisms flanking the BRCA1 gene

    SciTech Connect

    Bennett-Baker, P.E.; Kiousis, S.; King, S.E.

    1996-02-15

    This article reports on the isolation of tetranucleotide repeat polymorphisms which flank the BRCA1 gene on human chromosome 17. BRCA1 has been linked to both hereditary breast and ovarian cancer. Fifteen new short tandem repeat polymorphisms (STRPs) flanking the BRCA1 locus are reported. 18 refs., 2 figs., 1 tab.

  19. 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

  20. [Functional polymorphisms in clock genes and circadian rhythm sleep disorders].

    PubMed

    Ebisawa, Takashi

    2007-06-01

    Polymorphisms in clock genes induce circadian rhythm sleep disorders. Mutations in Per2 gene (S662G) or Casein Kinasel delta (CK16) gene (T44A) cause Familial advanced sleep phase syndrome. Missense polymorphisms in Per3 (V647G) and CK1e (S408N) genes increase or decrease the risk of developing delayed sleep phase syndrome. All of these polymorphisms seem to affect the phosphorylation of the clock proteins. Some of the polymorphisms in CK1, which shows reduced enzyme activity in vitro, induced increased phosphorylation of PER proteins in in vivo assays. Careful attention should be paid to analyze the complex system composed of feedback loops, such as the biological clock. PMID:17633519

  1. Negative Skeletal Effects of Locally Produced Adiponectin

    PubMed Central

    Abbott, Marcia J.; Roth, Theresa M.; Ho, Linh; Wang, Liping; O’Carroll, Dylan; Nissenson, Robert A.

    2015-01-01

    Epidemiological studies show that high circulating levels of adiponectin are associated with low bone mineral density. The effect of adiponectin on skeletal homeostasis, on osteoblasts in particular, remains controversial. We investigated this issue using mice with adipocyte-specific over-expression of adiponectin (AdTg). MicroCT and histomorphometric analysis revealed decreases (15%) in fractional bone volume in AdTg mice at the proximal tibia with no changes at the distal femur. Cortical bone thickness at mid-shafts of the tibia and at the tibiofibular junction was reduced (3–4%) in AdTg mice. Dynamic histomorphometry at the proximal tibia in AdTg mice revealed inhibition of bone formation. AdTg mice had increased numbers of adipocytes in close proximity to trabecular bone in the tibia, associated with increased adiponectin levels in tibial marrow. Treatment of BMSCs with adiponectin after initiation of osteoblastic differentiation resulted in reduced mineralized colony formation and reduced expression of mRNA of osteoblastic genes, osterix (70%), Runx2 (52%), alkaline phosphatase (72%), Col1 (74%), and osteocalcin (81%). Adiponectin treatment of differentiating osteoblasts increased expression of the osteoblast genes PPARγ (32%) and C/ebpα (55%) and increased adipocyte colony formation. These data suggest a model in which locally produced adiponectin plays a negative role in regulating skeletal homeostasis through inhibition of bone formation and by promoting an adipogenic phenotype. PMID:26230337

  2. 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

  3. 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

  4. 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

  5. Gene expression levels of Casein kinase 1 (CK1) isoforms are correlated to adiponectin levels in adipose tissue of morbid obese patients and site-specific phosphorylation mediated by CK1 influences multimerization of adiponectin.

    PubMed

    Xu, Pengfei; Fischer-Posovszky, Pamela; Bischof, Joachim; Radermacher, Peter; Wabitsch, Martin; Henne-Bruns, Doris; Wolf, Anna-Maria; Hillenbrand, Andreas; Knippschild, Uwe

    2015-05-01

    White adipose tissue has now been recognized as an important endocrine organ secreting bioactive molecules termed adipocytokines. In obesity, anti-inflammatory adipocytokines like adiponectin are decreased while pro-inflammatory factors are over-produced. These changes contribute to the development of insulin resistance and obesity-associated diseases. Since members of the casein kinase 1 (CK1) family are involved in the regulation of various signaling pathways we ask here whether they are able to modulate the functions of adiponectin. We show that CK1δ and ε are expressed in adipose tissue and that the expression of CK1 isoforms correlates with that of adiponectin. Furthermore, adiponectin co-immunoprecipitates with CK1δ and CK1ε and is phosphorylated by CK1δ at serine 174 and threonine 235, thereby influencing the formation of adiponectin oligomeric complexes. Furthermore, inhibition of CK1δ in human adipocytes by IC261 leads to an increase in basal and insulin-stimulated glucose uptake. In summary, our data indicate that site-specific phosphorylation of adiponectin, especially at sites targeted by CK1δ in vitro, provides an additional regulatory mechanism for modulating adiponectin complex formation and function. PMID:25724478

  6. Inflammatory bowel disease: the role of inflammatory cytokine gene polymorphisms.

    PubMed Central

    Balding, Joanna; Livingstone, Wendy J; Conroy, Judith; Mynett-Johnson, Lesley; Weir, Donald G; Mahmud, Nasir; Smith, Owen P

    2004-01-01

    The mechanisms responsible for development of inflammatory bowel disease (IBD) have not been fully elucidated, although the main cause of disease pathology is attributed to up-regulated inflammatory processes. The aim of this study was to investigate frequencies of polymorphisms in genes encoding pro-inflammatory and anti-inflammatory markers in IBD patients and controls. We determined genotypes of patients with IBD (n= 172) and healthy controls (n= 389) for polymorphisms in genes encoding various cytokines (interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF), IL-10, IL-1 receptor antagonist). Association of these genotypes to disease incidence and pathophysiology was investigated. No strong association was found with occurrence of IBD. Variation was observed between the ulcerative colitis study group and the control population for the TNF-alpha-308 polymorphism (p= 0.0135). There was also variation in the frequency of IL-6-174 and TNF-alpha-308 genotypes in the ulcerative colitis group compared with the Crohn's disease group (p= 0.01). We concluded that polymorphisms in inflammatory genes are associated with variations in IBD phenotype and disease susceptibility. Whether the polymorphisms are directly involved in regulating cytokine production, and consequently pathophysiology of IBD, or serve merely as markers in linkage disequilibrium with susceptibility genes remains unclear. PMID:15223609

  7. 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

  8. 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

  9. 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

  10. Klotho gene polymorphisms are related to colorectal cancer susceptibility

    PubMed Central

    Liu, Chang; Cui, Wei; Wang, Li; Yan, Lei; Ruan, Xinjian; Liu, Yanfang; Jia, Xiaoyan; Zhang, Xia

    2015-01-01

    Aim: The purpose of this study was to investigate the relationship of Klotho gene G-395A and C1818T polymorphisms with colorectal cancer (CRC) susceptibility. Methods: 125 CRC patients and 125 controls were enrolled in the study. G-395A and C1818T polymorphisms were genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. Haploview software was utilized to conduct linkage disequilibrium and haplotype analysis. Odds ratio (OR) and 95% confidence interval (95% CI) were used to analyze the correlation of genotypes and haplotypes with CRC susceptibility. Results: AA and GA genotypes of G-395A polymorphisms were related with CRC risk (AA: OR = 4.161, 95% CI = 1.437-12.053; GA: OR = 1.958, 95% CI = 1.133-3.385). The frequency of A allele was much higher in case group, compared with controls (31.2% vs.17.6%) and the value of OR AND 95% CI suggested that A allele served as a risk factor for CRC (OR = 2.123, 95% CI = 1.393-3.236). Haplotypes analysis indicated that A-C and A-T haplotypes were significantly associated with risk of CRC (OR = 1.822, 95% CI = 1.124-2.954; OR = 2.877, 95% CI = 1.340-6.176). Conclusion: G-395A polymorphism of Klotho gene could increase the risk of CRC. PMID:26261651

  11. 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.

  12. 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…

  13. [APOE gene polymorphisms associated with Down syndrome in Colombian populations].

    PubMed

    Rengifo, Lucero; Gaviria, Duverney; Serrano, Herman

    2012-06-01

    Introduction.Gene APOEε4 allele polymorphisms have been examined in Down syndrome because of the relationship between (a) the E4 isoform and (b) the type of Alzheimer's dementia that appears in individuals with Down syndrome. This isoform is considered a risk factor for Alzheimer's disease development and has been associated with early death in Down syndrome. Objectives. The polymorphisms in the APOE gene were characterized for Down syndrome individuals and their parents, in order to detect associations between the APOE polymorphisms and Down syndrome. Materials and methods. APOE gene polymorphisms were detected by RFLP-PCR and analyzed in 134 young individuals with Down syndrome, 87 mothers and 54 fathers, residents of the departments of Quindío and Risaralda, Colombia. The controls were 525 healthy individuals. Results. The APOEε3 allele and ε3/ε3 genotype were most frequent in all the populations (83-90% and 70-78%). The allelic frequency of APOEε2 was very low and ε2/ε2 (3-7%) was absent in Down syndrome and their parents. The allele APOEε4 was more frequent (11% vs. 9%) in Down syndrome individuals than in the controls. Comparing the allelic and genotypic frequencies between the populations with Down syndrome and their parents with the controls using Pearson c2 test and Fisher's exact test odds ratio, no statistically significant differences were found. Conclusions. No statistically significant association was found between the polymorphisms of the APOE gene and Down syndrome. Sample size or ethnic influences may have affected these results. More studies are necessary with other Colombian populations to determine possible associations in other genes related to Alzheimer's disease.

  14. Androgen receptor gene mutation, rearrangement, polymorphism.

    PubMed

    Eisermann, Kurtis; Wang, Dan; Jing, Yifeng; Pascal, Laura E; Wang, Zhou

    2013-09-01

    Genetic aberrations of the androgen receptor (AR) caused by mutations, rearrangements, and polymorphisms result in a mutant receptor that has varied functions compared to wild type AR. To date, over 1,000 mutations have been reported in the AR with most of these being associated with androgen insensitivity syndrome (AIS). While mutations of AR associated with prostate cancer occur less often in early stage localized disease, mutations in castration-resistant prostate cancer (CRPC) patients treated with anti-androgens occur more frequently with 10-30% of these patients having some form of mutation in the AR. Resistance to anti-androgen therapy usually results from gain-of-function mutations in the LBD such as is seen with bicalutamide and more recently with enzalutamide (MDV3100). Thus, it is crucial to investigate these new AR mutations arising from drug resistance to anti-androgens and other small molecule pharmacological agents.

  15. Ped gene deletion polymorphism frequency in wild mice.

    PubMed

    Newmark, Judith A; Sacher, Frank; Jones, Gwilym S; Warner, Carol M

    2002-07-01

    The Ped gene influences the rate of cleavage of preimplantation embryos and their subsequent survival. Embryos that express the product of the Ped gene, Qa-2 protein, cleave at a faster rate than embryos with an absence of Qa-2 protein. In addition, the Ped gene has pleiotropic effects on reproduction. Thus, there is a reproductive advantage to those mouse strains that are Qa-2 positive. The presence or absence of Qa-2 is reflected at the DNA level by the presence or absence (deletion polymorphism) of the gene(s) encoding Qa-2 protein. Many inbred and wild-derived mouse strains have been characterized as Qa-2 positive or negative, but no previous studies have looked at the distribution of the Ped gene in a population of free-living wild mice. The purpose of this study was to determine the Ped gene deletion polymorphism frequency in a sample of free-living wild mice. Twenty-nine mice were collected and identified as Mus musculus. Genomic DNA extraction was performed on tail tips, and PCR was used to amplify a region from the Ped gene. Known Qa-2 positive and negative mice were used as controls. Results showed that all 29 wild mice were positive for the Ped gene. Since the Ped gene is dominant and provides a reproductive advantage, it is not surprising that all of the wild mice were Qa-2 positive. However, our assay could not distinguish homozygous from heterozygous mice. It is possible that the Qa-2 deletion polymorphism is segregating in the population, and a larger sample size would identify some Qa-2 negative mice. PMID:12115912

  16. 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

  17. NBN Gene Polymorphisms and Cancer Susceptibility: A Systemic Review

    PubMed Central

    Berardinelli, Francesco; di Masi, Alessandra; Antoccia, Antonio

    2013-01-01

    The relationship between DNA repair failure and cancer is well established as in the case of rare, high penetrant genes in high cancer risk families. Beside this, in the last two decades, several studies have investigated a possible association between low penetrant polymorphic variants in genes devoted to DNA repair pathways and risk for developing cancer. This relationship would be also supported by the observation that DNA repair processes may be modulated by sequence variants in DNA repair genes, leading to susceptibility to environmental carcinogens. In this framework, the aim of this review is to provide the reader with the state of the art on the association between common genetic variants and cancer risk, limiting the attention to single nucleotide polymorphisms (SNPs) of the NBN gene and providing the various odd ratios (ORs). In this respect, the NBN protein, together with MRE11 and RAD50, is part of the MRN complex which is a central player in the very early steps of sensing and processing of DNA double-strand breaks (DSBs), in telomere maintenance, in cell cycle control, and in genomic integrity in general. So far, many papers were devoted to ascertain possible association between common synonymous and non-synonymous NBN gene polymorphisms and increased cancer risk. However, the results still remain inconsistent and inconclusive also in meta-analysis studies for the most investigated E185Q NBN miscoding variant. PMID:24396275

  18. 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.

  19. 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

  20. 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

  1. Association of PTEN gene polymorphisms with liver cancer risk

    PubMed Central

    Li, Hong-Guang; Liu, Fang-Feng; Zhu, Hua-Qiang; Zhou, Xu; Lu, Jun; Chang, Hong; Hu, Jin-Hua

    2015-01-01

    Objective: To find out if there are any relationship between three single nucleotide polymorphisms (SNPs) of phosphatase and tensin homolog (PTEN) gene (rs1234213, rs1234220, and rs2299939) and the susceptibility of liver cancer. Methods: Genotypes of the three SNPs in the PTEN gene were achieved utilizing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Comparison of genotypes and alleles distribution differences between the case and the control subjects was accomplished with χ2 test. The analysis of linkage disequilibrium (LD) and haplotypes of the three SNPs was performed using SHEsis software. We adopted odds ratios (ORs) with 95% confidence intervals (95% CIs) to show the relative risk of liver cancer. Results: TC genotype and C allele of rs1234220 polymorphism showed much more frequently in cases than in controls, reflecting that the TC genotype and the C allele may be linked to the increased risk of liver cancer (OR=2.225, 95% CI=1.178-4.204; OR=1.941, 95% CI=1.124-3.351). Rs2299939 polymorphism showed an opposite result that the GT genotype probably reduce the risk of liver cancer (OR=0.483, 95% CI=0.259-0.900). Statistical significance was not found in the distribution differences of the genotypes of rs1234213 between two groups. LD and haplotype analysis results of the three SNPs showed that the T-C-G haplotype frequency was much higher in cases than in healthy objects, which proved that the T-C-G haplotype might be a susceptibility haplotype for liver cancer (OR=3.750, 95% CI=1.396-10.077). Conclusions: PTEN gene polymorphisms might relate to liver cancer risk. PMID:26823866

  2. Structure and genetic polymorphism of the mouse KCC1 gene.

    PubMed

    Shmukler, B E; Brugnara, C; Alper, S L

    2000-07-24

    The KCC1 K-Cl cotransporter is a major regulator of erythroid and non-erythroid cell volume, and the KCC1 gene is a candidate modifier gene for sickle cell disease and other hemoglobinopathies. We have cloned and sequenced the mouse KCC1 (mKCC1) gene, defined its intron-exon junctions, and analyzed (AC)/(TG) intragenic polymorphisms. A highly polymorphic (AC) repeat of mKCC1 intron 1 was characterized in musculus strains, and used to prove lack of linkage between the mKCC1 gene and the rol (resistant to osmotic lysis) locus. The intron 1 (AC) repeat in CAST/Ei and SPRET/Ei was not only more divergent in length but also underwent additional sequence variation. A dimorphic (TG) repeat in intron 2 distinguished CAST/Ei from other strains, and an intron 17 B1 Alu-like SINE present in all musculus strains was found to be absent from intron 17 in SPRET/Ei. These and additional described strain-specific polymorphisms will be useful mapping and genetic tools in the study of mouse models of sickle cell disease.

  3. 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

  4. 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...

  5. 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

  6. [MOLECULAR-GENETIC POLYMORPHISM OF chs_H1 GENE IN UKRAINIAN HOP VARIETIES].

    PubMed

    Venzer, A M; Volkova, N E; Sivolap, Yu M

    2015-01-01

    Polymorphism of chs_H1 gene encoding the "true" chalcone synthase was determined by alignment of sequences. The polymorphism associates with single nucleotide changes, insertions or deletions (indels) in the promoter, exons, intron, 3'-untranslated region. The molecular-genetic polymorphism in gene chs_H1 different regions of hop varieties of Polessye Agriculture Institute' breeding NAAS was analyzed. PMID:26638493

  7. Interleukin 17 receptor gene polymorphism in periimplantitis and chronic periodontitis.

    PubMed

    Kadkhodazadeh, Mahdi; Ebadian, Ahmad Reza; Amid, Reza; Youssefi, Navid; Mehdizadeh, Amir Reza

    2013-01-01

    Gene polymorphism of cytokines influencing their function has been known as a contributing factor in the pathogenesis of inflammatory diseases of the tooth and implant supporting tissues. The aim of this study was to investigate the association of IL-17R gene polymorphism (rs879576) with chronic periodontitis and periimplantitis in an Iranian population. 73 patients with chronic periodontitis, 37 patients with periimplantitis and 83 periodontally healthy patients were enrolled in this study. 5cc blood was obtained from each subject's arm vein and transferred to tubes containing EDTA. Genomic DNA was extracted using Miller's Salting Out technique. The DNA was transferred into 96 division plates, transported to Kbioscience Institute in United Kingdom and analyzed using the Kbioscience Competitive Allele Specific PCR (KASP) technique. Chi-square and Kruskal Wallis tests were used to analyze differences in the expression of genotypes and frequency of alleles in disease and control groups (P-Value less than 0.05 was considered statistically significant). There were no significant differences between periodontitis, periimplantitis with AA, GG, GA genotype of IL-17R gene (P=0.8239). Also comparison of frequency of alleles in SNP rs879576 of IL-17R gene between the chronic periodontitis group and periimplantitis group did not revealed statistically significant differences (P=0.8239). The enigma of IL-17 and its polymorphism-role in periodontitis and periimplantitis is yet to be investigated more carefully throughout further research but this article demonstrates that polymorphism of IL-17R plays no significant role in incidence of chronic periodontitis and Periimplantitis. PMID:23852838

  8. Nuclear gene indicates coat-color polymorphism in mammoths.

    PubMed

    Römpler, Holger; Rohland, Nadin; Lalueza-Fox, Carles; Willerslev, Eske; Kuznetsova, Tatyana; Rabeder, Gernot; Bertranpetit, Jaume; Schöneberg, Torsten; Hofreiter, Michael

    2006-07-01

    By amplifying the melanocortin type 1 receptor from the woolly mammoth, we can report the complete nucleotide sequence of a nuclear-encoded gene from an extinct species. We found two alleles and show that one allele produces a functional protein whereas the other one encodes a protein with strongly reduced activity. This finding suggests that mammoths may have been polymorphic in coat color, with both dark- and light-haired individuals co-occurring.

  9. Polymorphism of visual pigment genes in the muriqui (Primates, Atelidae).

    PubMed

    Talebi, M G; Pope, T R; Vogel, E R; Neitz, M; Dominy, N J

    2006-02-01

    Colour vision varies within the family Atelidae (Primates, Platyrrhini), which consists of four genera with the following cladistic relationship: {Alouatta[Ateles (Lagothrix and Brachyteles)]}. Spider monkeys (Ateles) and woolly monkeys (Lagothrix) are characteristic of platyrrhine monkeys in possessing a colour vision polymorphism. The polymorphism results from allelic variation of the single-locus middle-to-long wavelength (M/L) cone opsin gene on the X-chromosome. The presence in the population of alleles coding for different M/L photopigments results in a variety of colour vision phenotypes. Such a polymorphism is absent in howling monkeys (Alouatta), which, alone among platyrrhines, acquired uniform trichromatic vision similar to that of Old World monkeys, apes, and humans through opsin gene duplication. Dietary and morphological similarities between howling monkeys and muriquis (Brachyteles) raise the possibility that the two genera share a similar form of colour vision, uniform trichromacy. Yet parsimony predicts that the colour vision of Brachyteles will resemble the polymorphism present in Lagothrix and Ateles. Here we test this assumption. We obtained DNA from the blood or faeces of 18 muriquis and sequenced exons 3 and 5 of the M/L opsin gene. Our results affirm the existence of a single M/L cone opsin gene in the genus Brachyteles. We detected three alleles with predicted lambdamax values of 530, 550, and 562 nm. Two females were heterozygous and are thus predicted to have different types of M/L cone pigment. We discuss the implication of this result towards understanding the evolutionary ecology of trichromatic vision.

  10. Polymorphism of visual pigment genes in the muriqui (Primates, Atelidae).

    PubMed

    Talebi, M G; Pope, T R; Vogel, E R; Neitz, M; Dominy, N J

    2006-02-01

    Colour vision varies within the family Atelidae (Primates, Platyrrhini), which consists of four genera with the following cladistic relationship: {Alouatta[Ateles (Lagothrix and Brachyteles)]}. Spider monkeys (Ateles) and woolly monkeys (Lagothrix) are characteristic of platyrrhine monkeys in possessing a colour vision polymorphism. The polymorphism results from allelic variation of the single-locus middle-to-long wavelength (M/L) cone opsin gene on the X-chromosome. The presence in the population of alleles coding for different M/L photopigments results in a variety of colour vision phenotypes. Such a polymorphism is absent in howling monkeys (Alouatta), which, alone among platyrrhines, acquired uniform trichromatic vision similar to that of Old World monkeys, apes, and humans through opsin gene duplication. Dietary and morphological similarities between howling monkeys and muriquis (Brachyteles) raise the possibility that the two genera share a similar form of colour vision, uniform trichromacy. Yet parsimony predicts that the colour vision of Brachyteles will resemble the polymorphism present in Lagothrix and Ateles. Here we test this assumption. We obtained DNA from the blood or faeces of 18 muriquis and sequenced exons 3 and 5 of the M/L opsin gene. Our results affirm the existence of a single M/L cone opsin gene in the genus Brachyteles. We detected three alleles with predicted lambdamax values of 530, 550, and 562 nm. Two females were heterozygous and are thus predicted to have different types of M/L cone pigment. We discuss the implication of this result towards understanding the evolutionary ecology of trichromatic vision. PMID:16448420

  11. Effect of gene polymorphisms on periodontal diseases

    PubMed Central

    Tarannum, Fouzia; Faizuddin, Mohamed

    2012-01-01

    Periodontal diseases are inflammatory diseases of supporting structures of the tooth. It results in the destruction of the supporting structures and most of the destructive processes involved are host derived. The processes leading to destruction and regeneration of the destroyed tissues are of great interest to both researchers and clinicians. The selective susceptibility of subjects for periodontitis has remained an enigma and wide varieties of risk factors have been implicated for the manifestation and progression of periodontitis. Genetic factors have been a new addition to the list of risk factors for periodontal diseases. With the availability of human genome sequence and the knowledge of the complement of the genes, it should be possible to identify the metabolic pathways involved in periodontal destruction and regeneration. Most forms of periodontitis represent a life-long account of interactions between the genome, behaviour, and environment. The current practical utility of genetic knowledge in periodontitis is limited. The information contained within the human genome can potentially lead to a better understanding of the control mechanisms modulating the production of inflammatory mediators as well as provides potential therapeutic targets for periodontal disease. Allelic variants at multiple gene loci probably influence periodontitis susceptibility. PMID:22754216

  12. Expression of adiponectin receptors in mouse adrenal glands and the adrenocortical Y-1 cell line: adiponectin regulates steroidogenesis.

    PubMed

    Li, Ping; Sun, Fei; Cao, Huang-Ming; Ma, Qin-Yun; Pan, Chun-Ming; Ma, Jun-Hua; Zhang, Xiao-Na; Jiang, He; Song, Huai-Dong; Chen, Ming-Dao

    2009-12-25

    Obesity is frequently associated with malfunctions of the hypothalamus-pituitary-adrenal (HPA) axis and hyperaldosteronism, but the mechanism underlying this association remains unclear. Since the adrenal glands are embedded in adipose tissue, direct cross-talk between adipose tissue and the adrenal gland has been proposed. A previous study found that adiponectin receptor mRNA was expressed in human adrenal glands and aldosterone-producing adenoma (APA). However, the expression of adiponectin receptors in adrenal glands has not been confirmed at the protein level or in other species. Furthermore, it is unclear whether adiponectin receptors expressed in adrenal cells are functional. We found, for the first time, that adiponectin receptor (AdipoR1 and AdipoR2) mRNA and protein were expressed in mouse adrenal and adrenocortical Y-1 cells. However, adiponectin itself was not expressed in mouse adrenal or Y-1 cells. Furthermore, adiponectin acutely reduced basal levels of corticosterone and aldosterone secretion. ACTH-induced steroid secretion was also inhibited by adiponectin, and this was accompanied by a parallel change in the expression of the key genes involved in steroidogenesis. These findings indicate that adiponectin may take part in the modulation of steroidogenesis. Thus, adiponectin is likely to have physiological and/or pathophysiological significance as an endocrine regulator of adrenocortical function.

  13. [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

  14. 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

  15. 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

  16. 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

  17. Breast cancer risk, nightwork, and circadian clock gene polymorphisms.

    PubMed

    Truong, Thérèse; Liquet, Benoît; Menegaux, Florence; Plancoulaine, Sabine; Laurent-Puig, Pierre; Mulot, Claire; Cordina-Duverger, Emilie; Sanchez, Marie; Arveux, Patrick; Kerbrat, Pierre; Richardson, Sylvia; Guénel, Pascal

    2014-08-01

    Night shift work has been associated with an increased risk of breast cancer pointing to a role of circadian disruption. We investigated the role of circadian clock gene polymorphisms and their interaction with nightwork in breast cancer risk in a population-based case-control study in France including 1126 breast cancer cases and 1174 controls. We estimated breast cancer risk associated with each of the 577 single nucleotide polymorphisms (SNPs) in 23 circadian clock genes. We also used a gene- and pathway-based approach to investigate the overall effect on breast cancer of circadian clock gene variants that might not be detected in analyses based on individual SNPs. Interactions with nightwork were tested at the SNP, gene, and pathway levels. We found that two SNPs in RORA (rs1482057 and rs12914272) were associated with breast cancer in the whole sample and among postmenopausal women. In this subpopulation, we also reported an association with rs11932595 in CLOCK, and with CLOCK, RORA, and NPAS2 in the analyses at the gene level. Breast cancer risk in postmenopausal women was also associated with overall genetic variation in the circadian gene pathway (P=0.04), but this association was not detected in premenopausal women. There was some evidence of an interaction between PER1 and nightwork in breast cancer in the whole sample (P=0.024), although the effect was not statistically significant after correcting for multiple testing (P=0.452). Our results support the hypothesis that circadian clock gene variants modulate breast cancer risk.

  18. 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

  19. 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.

  20. Polymorphic insertions and deletions in parabasalian enolase genes.

    PubMed

    Keeling, Patrick J

    2004-05-01

    Insertions and deletions in gene sequences have been used as characters to infer phylogenetic relationships and, like any character, the information they contain varies in utility between different levels of evolution. In one case, the absence of two otherwise highly conserved deletions in the enolase genes of parabasalian protists has been interpreted as a primitive characteristic that suggests these were among the first eukaryotes. Here, semi-environmental 3'-RACE was used to sample enolases from parabasalia in the hindgut of the termite Zootermopsis angusticolis to examine the conservation of this character within the parabasalia. Parabasalian homologues were found to be polymorphic for these deletions, and the phylogeny of parabasalian enolases shows that the deletion-possessing genes branch within deletion-lacking genes (i.e., they did not form two clearly distinct groups). Phylogenetic incongruence was detected in the carboxy-terminal third of the sequence (in the region of the deletions), but there is no unambiguous evidence for recombination. The polymorphism of this character discredits these deletions as strong evidence for the early origin of parabasalia, although the complex distribution makes it impossible to state whether parabasalian enolases were ancestrally like those of other eukaryotes. These observations stress the importance of strong corroborating evidence when considering insertion and deletion data, and raises some interesting questions about the apparent variation in degree of conservation of these deletions between different eukaryotic groups.

  1. 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

  2. Serotonin Transporter Gene Polymorphisms and Chronic Illness of Depression

    PubMed Central

    Myung, Woojae; Lim, Shinn-Won; Kim, Jinwoo; Lee, Yujin; Song, Jihye; Chang, Ki-won

    2010-01-01

    Clinical course of depression is variable. The serotonin transporter gene is one of the most studied genes for depression. We examined the association of serotonin transporter gene polymorphisms with chronicity and recurrent tendency of depression in Korean subjects. This cross-sectional study involved 252 patients with major depression. Patients were genotyped for s/l polymorphisms in 5-HTT promoter region (5-HTTLPR), s/l variation in second intron of the 5-HTT gene (5-HTT VNTR intron2). Chronicity was associated with 5-HTTLPR. Patients with l/l had higher rate of chronicity than the other patients (l/l vs s/l or s/s; odds ratio, 4.45; 95% confidence interval, 1.59-12.46; P=0.005; logistic regression analysis). Recurrent tendency was not associated with 5-HTTLPR. Chronicity and recurrent tendency were not associated with 5-HTT VNTR intron2. These results suggest that chronic depression is associated with 5-HTTLPR. PMID:21165304

  3. 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

  4. beta2 adrenoceptor gene polymorphisms in cystic fibrosis lung disease.

    PubMed

    Büscher, Rainer; Eilmes, Katrin Jennifer; Grasemann, Hartmut; Torres, Brian; Knauer, Nicola; Sroka, Karin; Insel, Paul A; Ratjen, Felix

    2002-07-01

    The cystic fibrosis membrane conductance regulator can be activated through beta2-adrenoceptor (beta2AR) stimulation. We tested the hypothesis that coding sequence polymorphisms in the beta2AR gene contribute to the disease state in patients with cystic fibrosis. The Arg16Gly, Gln27Glu, and Thr164Ile beta2AR polymorphisms were studied by specific polymerase chain reaction and restriction fragment length polymorphism analysis in 126 cystic fibrosis patients. Forced expiratory volume in 1 s was significantly (P < 0.05) reduced in cystic fibrosis patients carrying the Gly16 allele in either homozygous or heterozygous form (Gly16Gly + Arg16Gly) compared to patients homozygous for the Arg16 allele (60.3 +/- 3.5% versus 75.7 +/- 4.9% predicted). Similarly, forced vital capacity and flows at lower lung volumes were significantly (P < 0.05 and P < 0.01) lower in cystic fibrosis patients carrying the Gly16 allele. In addition, the Gly16 allele was associated with a greater 5 year decline in pulmonary function (P < 0.01). Bronchodilator responses to albuterol were not significantly different between the groups. The Thr164Ile variant was found in four patients; these patients had markedly reduced pulmonary function. Isoproterenol-stimulated cyclic AMP formation was significantly blunted in cystic fibrosis patients carrying either the Gly16 allele or Thr164Ile genotype compared to cystic fibrosis patients homozygous for the respective Arg16 alleles. These data provide the first evidence suggesting that polymorphisms of the beta2AR gene contribute to clinical severity and disease progression in cystic fibrosis.

  5. Interleukin-6 level and gene polymorphism in spontaneous miscarriage.

    PubMed

    Drozdzik, M; Szlarb, N; Kurzawski, M

    2013-09-01

    The aetiology of spontaneous miscarriage, the most common pregnancy complication, remains undefined. One of postulated factors involved in miscarriage pathology is interleukin 6 (IL-6). Therefore, the aim of the study was to evaluate IL-6 and interleukin 6 receptor (IL-6R) gene polymorphisms in patients with spontaneous miscarriage. One hundred fifty-seven patients diagnosed with spontaneous miscarriage and age and gestational time matched controls were included in the case-control study. In all study participants circulating IL-6 levels (chemiluminescent immunoassay) and IL6-174G>C as well as IL6R rs2228145:A>C polymorphisms were evaluated. The distribution of IL6 as well as IL6R alleles and genotypes were similar in the controls and patients with miscarriage. Only a trend of more frequent appearance of -174GC+CC and C allele in the patients with miscarriage was noted. Blood serum concentrations of IL-6 were significantly elevated in patients with miscarriage vs those with physiological pregnancy. Likewise, IL-6 concentrations differ significantly with the types of miscarriage. The highest concentrations of the cytokine was seen in subjects with incomplete miscarriage (4.28 ± 4.88 pg/ml) followed by imminent miscarriage (2.97 ± 2.42 pg/ml), and then missed miscarriage (2.07 ± 1.90 pg/ml), being significantly the lowest in missed miscarriage group. No association between the IL6 genotype and IL-6 serum concentration were noted, both in the miscarriage group and in the control group. The findings of the study support the role of IL-6 in spontaneous miscarriage irrespectively of its type. However, no correlation between circulating IL-6 and IL6 gene polymorphism, as well as IL-6 and IL-6R polymorphisms associations with spontaneous miscarriage were revealed.

  6. Gene Copy-Number Polymorphism Caused by Retrotransposition in Humans

    PubMed Central

    Galante, Pedro A. F.; Parmigiani, Raphael B.; Camargo, Anamaria A.; Hahn, Matthew W.; de Souza, Sandro J.

    2013-01-01

    The era of whole-genome sequencing has revealed that gene copy-number changes caused by duplication and deletion events have important evolutionary, functional, and phenotypic consequences. Recent studies have therefore focused on revealing the extent of variation in copy-number within natural populations of humans and other species. These studies have found a large number of copy-number variants (CNVs) in humans, many of which have been shown to have clinical or evolutionary importance. For the most part, these studies have failed to detect an important class of gene copy-number polymorphism: gene duplications caused by retrotransposition, which result in a new intron-less copy of the parental gene being inserted into a random location in the genome. Here we describe a computational approach leveraging next-generation sequence data to detect gene copy-number variants caused by retrotransposition (retroCNVs), and we report the first genome-wide analysis of these variants in humans. We find that retroCNVs account for a substantial fraction of gene copy-number differences between any two individuals. Moreover, we show that these variants may often result in expressed chimeric transcripts, underscoring their potential for the evolution of novel gene functions. By locating the insertion sites of these duplicates, we are able to show that retroCNVs have had an important role in recent human adaptation, and we also uncover evidence that positive selection may currently be driving multiple retroCNVs toward fixation. Together these findings imply that retroCNVs are an especially important class of polymorphism, and that future studies of copy-number variation should search for these variants in order to illuminate their potential evolutionary and functional relevance. PMID:23359205

  7. Transcription factor 4 gene rs9960767 polymorphism in bipolar disorder

    PubMed Central

    Ozel, Mavi Deniz; Onder, Mehmet Emin; Sazci, Ali

    2016-01-01

    The transcription factor 4 (TCF4) gene encodes a helix-loop-helix transcription factor protein, which initiates neuronal differentiation and is primarily expressed during nervous system development. The aim of the present study is to investigate the association of the TCF4 rs9960767 polymorphism and bipolar disorder, which is highly heritable. DNA isolation was performed on 95 patients with bipolar disorder and 108 healthy control subjects to examine the TCF4 rs9960767 polymorphism. Genotypic and allelic frequencies were determined using the polymerase chain reaction-restriction fragment length polymorphism method designed in our laboratory. Statistical analysis was performed using χ2 test within the 95% confidence interval. Odds ratios were calculated and Hardy-Weinberg equilibrium (HWE) was verified for all control subjects and patients. The A allele frequency was 95.8% in the patients and 94.4% in the control subjects, and 4.2% in the patients and 5.6% in the control subjects for the C allele. The genotype frequencies of the TCF4 gene rs9960767 variant were as follows: AA, 91.6% and AC, 8.4% in patients with bipolar (CC genotype was not observed in cases); AA, 89.8%; AC, 9.3% and CC, 0.9% in the control subjects. No statistically significant difference was identified between the patients and control subjects (χ2=0.937; P=0.626). In addition, gender specific analysis was performed, although no significant association was found according to the gender distrubition. All patients and control subjects were in HWE (P>0.05). Statistical analysis of the data indicates that the TCF4 gene rs9960767 polymorphism is not an independent risk factor for bipolar disorder in the overall population or in terms of gender; however, an increased population size would improve the statistical power. Furthermore, additional gene variants that are specifically involved in neuronal development may be analyzed for revealing the complex genetic architecture of bipolar disorder. An

  8. Transcription factor 4 gene rs9960767 polymorphism in bipolar disorder

    PubMed Central

    Ozel, Mavi Deniz; Onder, Mehmet Emin; Sazci, Ali

    2016-01-01

    The transcription factor 4 (TCF4) gene encodes a helix-loop-helix transcription factor protein, which initiates neuronal differentiation and is primarily expressed during nervous system development. The aim of the present study is to investigate the association of the TCF4 rs9960767 polymorphism and bipolar disorder, which is highly heritable. DNA isolation was performed on 95 patients with bipolar disorder and 108 healthy control subjects to examine the TCF4 rs9960767 polymorphism. Genotypic and allelic frequencies were determined using the polymerase chain reaction-restriction fragment length polymorphism method designed in our laboratory. Statistical analysis was performed using χ2 test within the 95% confidence interval. Odds ratios were calculated and Hardy-Weinberg equilibrium (HWE) was verified for all control subjects and patients. The A allele frequency was 95.8% in the patients and 94.4% in the control subjects, and 4.2% in the patients and 5.6% in the control subjects for the C allele. The genotype frequencies of the TCF4 gene rs9960767 variant were as follows: AA, 91.6% and AC, 8.4% in patients with bipolar (CC genotype was not observed in cases); AA, 89.8%; AC, 9.3% and CC, 0.9% in the control subjects. No statistically significant difference was identified between the patients and control subjects (χ2=0.937; P=0.626). In addition, gender specific analysis was performed, although no significant association was found according to the gender distrubition. All patients and control subjects were in HWE (P>0.05). Statistical analysis of the data indicates that the TCF4 gene rs9960767 polymorphism is not an independent risk factor for bipolar disorder in the overall population or in terms of gender; however, an increased population size would improve the statistical power. Furthermore, additional gene variants that are specifically involved in neuronal development may be analyzed for revealing the complex genetic architecture of bipolar disorder. An

  9. Angiotensin converting enzyme gene polymorphism in familial hypertrophic cardiomyopathy patients

    SciTech Connect

    Yu, B; Peric, S.; Ross, D.

    1994-09-01

    An insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme (ACE) gene is a useful predictor of human plasma ACE levels. ACE levels tend to be lowest in subjects with ACE genotype DD and intermediate in subjects with ACE genotype ID. Angiotensin II (Ang II) as a product of ACE is a cardiac growth factor and produces a marked hypertrophy of the chick myocyte in cell culture. Rat experiments also suggest that a small dose of ACE inhibitor that does not affect the afterload results in prevention or regression of cardiac hypertrophy. In order to study the relationship of ACE and the severity of hypertrophy, the ACE genotype has been determined in 28 patients with a clinical diagnosis of familial hypertrophic cardiomyopathy (FHC) and 51 normal subjects. The respective frequencies of I and D alleles were: 0.52 and 0.48 (in FHC patients) and 0.44 and 0.56 (in the normal controls). There was no significant difference in the allele frequencies between FHC and normal subjects ({chi}{sup 2}=0.023, p>0.05). The II, ID, and DD genotypes were present in 7, 15, and 6 FHC patients, respectively. The averages of maximal thickness of the interventricular septum measured by echocardiography or at autopsy were 18 {plus_minus}3, 19{plus_minus}4, and 19{plus_minus}3 mm in II, ID and DD genotypes, respectively. The ACE gene polymorphism did not correlate with the severity of left ventricular hypertrophy in FHC patients (r{sub s}=0.231, p>0.05). These results do not necessarily exclude the possible effect of Ang II on the hypertrophy since the latter may be produced through the action of chymase in the human ventricles. However, ACE gene polymorphism is not a useful predictor of the severity of myocardial hypertrophy in FHC patients.

  10. Pepsinogen C gene polymorphisms associated with gastric body ulcer.

    PubMed Central

    Azuma, T; Teramae, N; Hayakumo, T; Yasuda, K; Nakajima, M; Kodama, T; Inokuchi, H; Hayashi, K; Taggart, R T; Kawai, K

    1993-01-01

    This study was aimed to investigate the association of restriction fragment length polymorphisms (RFLPs) for pepsinogen genes with peptic ulcer disease. Eighty unrelated controls, 61 patients with gastric ulcer, and 57 patients with duodenal ulcer were studied. No genetic polymorphisms for pepsinogen A were detected by EcoRI digestion in Japanese subjects but a 100 base pairs insertion-deletion RFLP for the pepsinogen C gene was observed. The allele frequencies of the large (3.6 kilobase EcoRI fragment) and the small fragment (3.5 kilobase EcoRI fragment) were 80.6% and 19.4% respectively in controls, 55.4% and 44.6% in patients with gastric body ulcer, 79.4% and 20.6% in patients with gastric angular ulcer, 71.4% and 28.6% in patients with gastric antral ulcer, and 75.4% and 24.6% in patients with duodenal ulcer. The allele frequency of the small fragment was significantly higher in patients with gastric body ulcer than in controls and in patients with gastric angular or antral ulcer. The genotypes which possessed the small fragment were significantly more frequent in patients with gastric body ulcer (78.4%) than in controls (33.8%) and in patients with gastric angular or antral ulcer (37.5%). These results suggest that there is a significant association between the genetic polymorphism at the pepsinogen C gene locus and gastric body ulcer, and that the pepsinogen C RFLP is a useful marker of the genetic predisposition to this disorder. These results also indicate genetic heterogeneity of gastric ulcer disease, and suggest that the pepsinogen C RFLP may be a useful subclinical marker to explain the differences in genetic aetiologies of gastric body ulcer and gastric angular or antral ulcer. Images Figure 1 Figure 2 PMID:8098309

  11. Kappa casein gene polymorphism in local Tunisian goats.

    PubMed

    Jemmali, B; Ben Gara, A; Selmi, H; Ammari, Z; Bouheni, C; Ben Larbi, M; Hammami, M; Amraoui, M; Kamoun, M; Rouissi, H; Rekik, B

    2013-12-15

    The genetic polymorphism of the goat Kappa casein was investigated in Tunisian goats. Blood samples were collected from local goat breeds. Samples of genomic DNA were obtained from leukocytes of 175 dairy goats and regions of interest in the gene were amplified by Polymerase Chain Reaction (PCR) and then evaluated in agarose gel. For a better characterization of the single nucleotide polymorphism, a PCR-Restriction Fragment Length Polymorphism was performed employing the endonuclease DNA amplification using 459 bp primers. The PCR products of primers (459 bp) digested by restriction enzyme Alw44I produced two fragments of 459 and 381 bp. The Kappa casein allelic variants in tested animals revealed different genotypes, two of them were homozygous: AA or BB, AC or BC and CC. Genotypic frequencies were 12.5, 60.5 and 27% for AA or BB, CC and AC or BC, respectively. Identification of different variants of the Kappa casein can be used for the improvement and conservation of Tunisian local goats.

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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

  19. Cytokine Gene Polymorphisms and Outcome after Traumatic Brain Injury

    PubMed Central

    Waters, Ryan J.; Murray, Gordon D.; Teasdale, Graham M.; Stewart, Janice; Day, Ian; Lee, Robert J.

    2013-01-01

    Abstract Clinical outcome after traumatic brain injury (TBI) is variable and cannot easily be predicted. There is increasing evidence to suggest that there may be genetic influences on outcome. Cytokines play an important role in mediating the inflammatory response provoked within the central nervous system after TBI. This study was designed to identify associations between cytokine gene polymorphisms and clinical outcome 6 months after head injury. A prospectively identified cohort of patients (n=1096, age range 0–93 years, mean age 37) was used. Clinical outcome at 6 months was assessed using the Glasgow Outcome Scale. In an initial screen of 11 cytokine gene single nucleotide polymorphisms (SNPs) previously associated with disease susceptibility or outcome (TNFA −238 and −308, IL6 −174, −572 and −597, IL1A −889, IL1B −31, −511 and +3953, and TGFB −509 and −800), TNFA −308 was identified as having a likely association. The TNFA −308 SNP was further evaluated, and a significant association was identified, with 39% of allele 2 carriers having an unfavorable outcome compared with 31% of non-carriers (adjusted odds ratio 1.67, confidence interval 1.19–2.35, p=0.003). These findings are consistent with experimental and clinical data suggesting that neuroinflammation has an impact on clinical outcome after TBI and that tumor necrosis factor alpha plays an important role in this process. PMID:23768161

  20. Cytokine gene polymorphisms and outcome after traumatic brain injury.

    PubMed

    Waters, Ryan J; Murray, Gordon D; Teasdale, Graham M; Stewart, Janice; Day, Ian; Lee, Robert J; Nicoll, James A R

    2013-10-15

    Clinical outcome after traumatic brain injury (TBI) is variable and cannot easily be predicted. There is increasing evidence to suggest that there may be genetic influences on outcome. Cytokines play an important role in mediating the inflammatory response provoked within the central nervous system after TBI. This study was designed to identify associations between cytokine gene polymorphisms and clinical outcome 6 months after head injury. A prospectively identified cohort of patients (n=1096, age range 0-93 years, mean age 37) was used. Clinical outcome at 6 months was assessed using the Glasgow Outcome Scale. In an initial screen of 11 cytokine gene single nucleotide polymorphisms (SNPs) previously associated with disease susceptibility or outcome (TNFA -238 and -308, IL6 -174, -572 and -597, IL1A -889, IL1B -31, -511 and +3953, and TGFB -509 and -800), TNFA -308 was identified as having a likely association. The TNFA -308 SNP was further evaluated, and a significant association was identified, with 39% of allele 2 carriers having an unfavorable outcome compared with 31% of non-carriers (adjusted odds ratio 1.67, confidence interval 1.19-2.35, p=0.003). These findings are consistent with experimental and clinical data suggesting that neuroinflammation has an impact on clinical outcome after TBI and that tumor necrosis factor alpha plays an important role in this process.

  1. 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.

  2. Polymorphism in the interferon-{alpha} gene family

    SciTech Connect

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

    1996-09-01

    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 {open_quotes}nested{close_quotes} 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. 44 refs., 4 figs., 4 tabs.

  3. 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.

  4. Adiponectin induces NF-kappaB activation that leads to suppression of cytokine-induced NF-kappaB activation in vascular endothelial cells: globular adiponectin vs. high molecular weight adiponectin.

    PubMed

    Tomizawa, Atsuko; Hattori, Yoshiyuki; Kasai, Kikuo; Nakano, Yasuko

    2008-06-01

    Adiponectin circulates in plasma as various isoforms. However, the biological activity of each isoform has not been firmly established. High molecular weight (HMW) adiponectin may be the active form of adiponectin, while a proteolytic cleavage product of adiponectin, known as globular adiponectin (gAd), has recently been shown to activate vascular endothelial cells. We compared HMW adiponectin with gAd to investigate whether they could activate nuclear factor kappa B (NF-kappaB) and suppress cytokine-induced NF-kappaB activation in vascular endothelial cells. HMW adiponectin was found to activate NF-kB modestly compared to the activation observed with gAd. HMW adiponectin requires a shorter incubation period to demonstrate inhibition against tumour necrosis factor alpha (TNFalpha)-induced NF-kappaB activation, compared with gAd. gAd strongly activates NF-kappaB, thereby inducing the expression of various pro-inflammatory and adhesion molecule genes, and requires a longer incubation period to show inhibition against cytokine-induced NF-kappaB activation. Thus, HMW adiponectin might function to protect against inflammatory stimuli, while cleavage of adiponectin at inflammatory sites might enhance the inflammatory process.

  5. Impact of Adiponectin Overexpression on Allergic Airways Responses in Mice

    PubMed Central

    Verbout, Norah G.; Williams, Alison S.; Kasahara, David I.; Wurmbrand, Allison P.; Halayko, Andrew J.; Shore, Stephanie A.

    2013-01-01

    Obesity is an important risk factor for asthma. Obese individuals have decreased circulating adiponectin, an adipose-derived hormone with anti-inflammatory properties. We hypothesized that transgenic overexpression of adiponectin would attenuate allergic airways inflammation and mucous hyperplasia in mice. To test this hypothesis, we used mice overexpressing adiponectin (Adipo Tg). Adipo Tg mice had marked increases in both serum adiponectin and bronchoalveolar lavage (BAL) fluid adiponectin. Both acute and chronic ovalbumin (OVA) sensitization and challenge protocols were used. In both protocols, OVA-induced increases in total BAL cells were attenuated in Adipo Tg versus WT mice. In the acute protocol, OVA-induced increases in several IL-13 dependent genes were attenuated in Adipo Tg versus WT mice, even though IL-13 per se was not affected. With chronic exposure, though OVA-induced increases in goblet cells numbers per millimeter of basement membrane were greater in Adipo Tg versus WT mice, mRNA abundance of mucous genes in lungs was not different. Also, adiponectin overexpression did not induce M2 polarization in alveolar macrophages. Our results indicate that adiponectin protects against allergen-induced inflammatory cell recruitment to the airspaces, but not development of goblet cell hyperplasia. PMID:23861690

  6. [LEP gene allelic polymorphism in a subpopulation of Ayrshire cattle].

    PubMed

    Kovaljuk, N V; Satsuk, V F; Volchenko, A E; Machulskaja, E V

    2015-02-01

    Genotyping of the leptin gene locus (LEP) (SNP: R25C, Y7F, and A80V) has been conducted in cows from two cattle droves (n = 106 and n = 34) and in bulls of Ayrshire cattle (n = 9) that are intensively used at present for artificial insemination in cows in Krasnodar krai. The absence of A80V polymorphism (C --> T at position 95691973 bp of leptin gene) has been established in the genotypes of Ayrshire cattle as compared to Holstein cattle; however, the F allele (Y7F site A --> T at position 95689996 bp of LEP gene), which is rare in Holstein cattle, was shown to be frequent in Ayrshire cows and producer bulls (with a frequency of 0.22-0.79). The heterozygosity did not exceed 0.11 in adult animals, which might be evidence of a decreased vitality in animals bearing the FF genotype. Moreover, the CC genotype (R25C site T-C at position 95690050 bp of LEP gene) was revealed to be linked to the YY genotype (Y7F site) in 97% of cases from possible combinations of the CCYY, CCYF, and CCFF genotypes, while the FF genotype (Y7F site) was observed to be linked to the RR genotype (R25C site) in 100% of cases of possible combinations of FFCC, FFRC, and FFRR genotypes.

  7. Serotonin transporter gene polymorphisms and treatment-resistant depression.

    PubMed

    Bonvicini, Cristian; Minelli, Alessandra; Scassellati, Catia; Bortolomasi, Marco; Segala, Matilde; Sartori, Riccardo; Giacopuzzi, Mario; Gennarelli, Massimo

    2010-08-16

    Major Depression Disorder (MDD) is a serious mental illness that is one of the most disabling diseases worldwide. In addition, approximately 15% of depression patients are defined treatment-resistant (TRD). Preclinical and genetic studies show that serotonin modulation dysfunction exists in patients with TRD. Some polymorphisms in the promoter region of the serotonin transporter gene (SLC6A4) are likely to be involved in the pathogenesis/treatment of MDD; however, no data are available concerning TRD. Therefore, in order to investigate the possible influence of SLC6A4 polymorphisms on the risk of TRD, we genotyped 310 DSM-IV MDD treatment-resistant patients and 284 healthy volunteers. We analysed the most studied polymorphism 5-HTTLPR (L/S) and a single nucleotide substitution, rs25531 (A/G), in relation to different functional haplotype combinations. However the correct mapping of rs25531 is still debated whether it is within or outside the insertion. Our sequencing analysis showed that rs25531 is immediately outside of the 5-HTTLPR segment. Differences in 5-HTTLPR allele (p=0.04) and in L allele carriers (p<0.05) were observed between the two groups. Concerning the estimated haplotype analyses, L(A)L(A) homozygote haplotype was more represented among the control subjects (p=0.01, OR=0.64 95%CI: 0.45-0.91). In conclusion, this study reports a protective effect of the L(A)L(A) haplotype on TRD, supporting the hypothesis that lower serotonin transporter transcription alleles are correlated to a common resistant depression mechanism.

  8. 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

  9. Preterm birth and single nucleotide polymorphisms in cytokine genes

    PubMed Central

    Zhu, Qin; Sun, Jian

    2014-01-01

    Preterm birth (PTB) is an important issue in neonates because of its complications as well as high morbidity and mortality. The prevalence of PTB is approximately 12-13% in USA and 5-9% in many other developed countries. China represents 7.8% (approximately one million) of 14.9 million babies born prematurely annually worldwide. The rate of PTB is still increasing. Both genetic susceptibility and environmental factors are the major causes of PTB. Inflammation is regarded as an enabling characteristic factor of PTB. The aim of this review is to summarize the current literatures to illustrate the role of single nucleotide polymorphisms (SNPs) of cytokine genes in PTB. These polymorphisms are different among different geographic regions and different races, thus different populations may have different risk factors of PTB. SNPs affect the ability to metabolize poisonous substances and determine inflammation susceptibility, which in turn has an influence on reproduction-related risks and on delivery outcomes after exposure to environmental toxicants and pathogenic organisms. PMID:26835330

  10. 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

  11. Association of interleukin-6 gene polymorphism with angina pectoris.

    PubMed

    Amorim, Fernanda Gobbi; Campagnaro, Bianca Prandi; Tonini, Clarissa Loureiro; Norbim, Ana Paula Capua; Louro, Iuri Drummond; Vasquez, Elisardo Corral; Arruda, Jose Airton; Meyrelles, Silvana Santos

    2011-10-01

    In this study, we investigated the role of the -174G>C polymorphism of interleukin-6 (IL-6) as a predisposing factor to angina pectoris. Patients were separated into 2 groups: angina (N = 72) and nonangina (N = 71). There were no statistical differences between groups for all cardiovascular risk factors evaluated. The GG genotype frequency was 18% lower in the angina than in the non-angina group, whereas GC + CC was 18% higher in the angina group (P = .036). The frequency of G allele was 11% lower in the angina than in the nonangina group and C allele was 11% higher in the angina group (P = .043). Patients carrying the C allele showed a 2-fold increased risk for angina pectoris (P = .036). Our study demonstrates a high incidence of the -174G>C polymorphism of the IL-6 gene in patients with angina pectoris compared with those carrying the G allele, reinforcing the contribution of genetic factors to the symptoms of angina pectoris.

  12. 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

  13. 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

  14. 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.

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

    PubMed

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

    2016-09-12

    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.

  16. 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.

  17. Cloning and Polymorphisms of Yak Lactate Dehydrogenase b Gene

    PubMed Central

    Wang, Guosheng; Zhao, Xingbo; Zhong, Juming; Cao, Meng; He, Qinghua; Liu, Zhengxin; Lin, Yaqiu; Xu, Yaou; Zheng, Yucai

    2013-01-01

    The main objective of this work was to study the unique polymorphisms of the lactate dehydrogenase-1 (LDH1) gene in yak (Bos grunniens). Native polyacrylamide gel electrophoresis revealed three phenotypes of LDH1 (a tetramer of H subunit) in yak heart and longissimus muscle extracts. The corresponding gene, ldhb, encoding H subunits of three LDH1 phenotypes was obtained by RT-PCR. A total of six nucleotide differences were detected in yak ldhb compared with that of cattle, of which five mutations cause amino acid substitutions. Sequence analysis shows that the G896A and C689A, mutations of ldhb gene, result in alterations of differently charged amino acids, and create the three phenotypes (F, M, and S) of yak LDH1. Molecular modeling of the H subunit of LDH indicates that the substituted amino acids are not located within NAD+ or substrate binding sites. PCR-RFLP examination of G896A mutation demonstrated that most LDH1-F samples are actually heterozygote at this site. These results help to elucidate the molecular basis and genetic characteristic of the three unique LDH1 phenotypes in yak. PMID:23739677

  18. 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.

  19. 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

  20. Organization, structure, and polymorphisms of the human profilaggrin gene.

    PubMed

    Gan, S Q; McBride, O W; Idler, W W; Markova, N; Steinert, P M

    1990-10-01

    Profilaggrin is a major protein component of the keratohyalin granules of mammalian epidermis. It is initially expressed as a large polyprotein precursor and is subsequently proteolytically processed into individual functional filaggrin molecules. We have isolated genomic DNA and cDNA clones encoding the 5'- and 3'-ends of the human gene and mRNA. The data reveal the presence of likely "CAT" and "TATA" sequences, an intron in the 5'-untranslated region, and several potential regulatory sequences. While all repeats are of the same length (972 bp, 324 amino acids), sequences display considerable variation (10-15%) between repeats on the same clone and between different clones. Most variations are attributable to single-base changes, but many also involve changes in charge. Thus, human filaggrin consists of a heterogeneous population of molecules of different sizes, charges, and sequences. However, amino acid sequences encoding the amino and carboxyl termini are more conserved, as are the 5' and 3' DNA sequences flanking the coding portions of the gene. The presence of unique restriction enzyme sites in these conserved flanking sequences has enabled calculations on the size of the full-length gene and the numbers of repeats in it: depending on the source of genomic DNA, the gene contains 10, 11, or 12 filaggrin repeats that segregate in kindred families by normal Mendelian genetic mechanisms. This means that the human profilaggrin gene system is also polymorphic with respect to size due to simple allelic differences between different individuals. The amino- and carboxyl-terminal sequences of profilaggrin contain partial or truncated repeats with unusual un-filaggrin-like sequences on the termini.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. 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

  2. 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

  3. 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

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

    PubMed

    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

  5. 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

  6. Molecular genetics of Psoriasis (Principles, technology, gene location, genetic polymorphism and gene expression)

    PubMed Central

    Al Robaee, Ahmad A.

    2010-01-01

    Summary: Psoriasis is a common inflammatory skin disease with an etiology bases on both environmental and genetic factors. As is the case of many autoimmune diseases its real cause remains poorly defined. However, it is known that genetic factors contribute to disease susceptibility. The linkage analysis has been used to identify multiple loci and alleles that confer risk of the disease. Some other studies have focused upon single nucleotide polymorphisms (SNPs) for mapping of probable causal variants. Other studies, using genome-wide analytical techniques, tried to link the disease to copy number variants (CNVs) that are segments of DNA ranging in size from kilobases to megabases that vary in copy number. CNVs represent an important element of genomic polymorphism in humans and harboring dosage-sensitive genes may cause or predispose to a variety of human genetic diseases. The mechanisms giving rise to SNPs and CNVs can be considered as fundamental processes underlying gene duplications, deletions, insertions, inversions and complex combinations of rearrangements. The duplicated genes being the results of ‘successful’ copies are fixed and maintained in the population. Conversely, many ‘unsuccessful’ duplicates remain in the genome as pseudogenes. There is another form of genetic variations termed copy-neutral loss of heterozygosity (LOH) with less information about their potential impact on complex diseases. Additional studies would include associated gene expression variations with either SNPs or CNVs. Now many genetic techniques such as PCR, real time PCR, microarray and restriction fragment length analysis are available for detecting genetic polymorphisms, gene mapping and estimation of gene expression. Recently, the scientists have used these tools to define genetic signatures of disease, to understand genetic causes of disease and to characterize the effects of certain drugs on gene expression. This review highlights the principles, technology and

  7. [Influence of polymorphism's of endothelial nitric oxide synthase gene and polymorphism of NADPH oxidase gene on development of complications of arterial hypertension].

    PubMed

    Kuznetsova, T Iu; Gavrilov, D V; Dudanov, I P; Makarevich, P I; Balatskiĭ, A V; Samokhodskaia, L M; Parfenova, E V

    2008-01-01

    The aim of the study was to analyze the prevalence of polymorphism Glu298Asp of endothelial nitric oxide synthase gene and C242T p22 phox polymorphism of NADPH oxidase gene in patients with arterial hypertension (AH) and their influence on AH complications. The study included 272 AH patients, average age 50,7 years. The following analyses were performed: clinical analysis of the blood, general analysis of the urine, lipid spectrum, plasma electrolytes, creatinine, glucose, electrocardiography, echocardioscopy, examination of eye vessels, ultrasound examination of the carotid arteries, determination of microalbuminuria. The polymorphism Glu298Asp of endothelial nitric oxide synthase gene and C242T p22 phox polymorphism of NADPH oxidase gene were detected with two methods: polymerase chain reaction and restrictase reaction. The control group for Glu298Asp polymorphism detection included 102 healthy Russian donors aged 18 to 50 years. Genotypes prevalence in AH patients was as follows: GG 58,8%, GA 32,3%, AA 8,9%, and CC 48,2%, CT 44,9%, TT 6.9%. In the control group: GG 53%, GA 36%, AA 11% and CC 42%, CT 54%, TT 4%. These polymorphisms did not affect the incidence of complications, such as obliterating atherosclerosis of the lower extremity vessels, ischemic heart disease, and acute insufficiency of cerebral circulation, chronic heart failure, left ventricular hypertrophy, microalbuminuria, carotid arteries atherosclerosis. PMID:18429753

  8. 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

  9. 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

  10. Molecular Polymorphism in the Period Gene of Drosophila Simulans

    PubMed Central

    Rosato, E.; Peixoto, A. A.; Barbujani, G.; Costa, R.; Kyriacou, C. P.

    1994-01-01

    The threonine-glycine (Thr-Gly) repeat region of the period (per) gene of eight natural populations of Drosophila simulans from Europe and North Africa was analyzed by polymerase chain reaction, DNA sequencing and heteroduplex formation. Five different length alleles encoding 21, 23, 25 and two different kinds of 24 Thr-Gly pairs in the uninterrupted repeat were found. In the 3' region flanking the repeat 6 nucleotide substitutions (3 synonymous, 3 replacement) were observed in three different combinations that we called haplotypes I, II and III. The complete linkage disequilibrium observed between the haplotypes and these length variants allowed us to infer from the repeat length, the DNA sequence at the 3' polymorphic sites. The haplotypes were homogeneously distributed across Europe and North Africa. The data show statistically significant departures from neutral expectations according to the Tajima test. The results suggest that balancing selection might have played a role in determining the observed levels and patterns of genetic diversity at the per gene in D. simulans. PMID:7851767

  11. A Candidate Gene Association Study of 77 Polymorphisms in Migraine

    PubMed Central

    Schürks, Markus; Kurth, Tobias; Buring, Julie E.; Zee, Robert Y.L.

    2009-01-01

    Population-based studies have established an association between migraine and cardiovascular disease (CVD). We sought to investigate whether genetic variants implicated in CVD are associated with migraine. We performed an association study among 25,713 women, participating in the Women’s Health Study, with information on 77 previously characterized polymorphisms. Migraine and migraine aura status were self-reported. We used logistic regression to investigate the genotype-migraine association. At baseline, 4,705 (18.3%) women reported history of migraine; 39.6% of the 3,306 women with active migraine indicated aura. Regarding any history of migraine, the multivariable-adjusted odds ratios (95% confidence intervals) for TNF rs673 were 0.52 (0.30-0.89), for TGFB1 rs1800469 0.93 (0.89-0.98), and for CCR2 rs1799864 1.12 (1.03-1.21). Among active migraine with aura the odds ratios (95% confidence intervals) were 1.35 (1.0-1.81) for TNF rs1800750, 1.13 (1.02-1.26) for TNF rs1800629, and 1.22 (1.07-1.40) for CCR2 rs1799864; among active migraine without aura 0.9 (0.84-0.97) for TGFB1 rs1800469, 1.13 (1.01-1.27) for NOS3 rs3918226, and 1.12 (1.02-1.24) for IL9 rs2069885. After correction for multiple testing using the false discovery rate, none of the results remained significant. Our data suggest an association of polymorphisms implicated in inflammatory pathways and migraine in women. TNF, CCR2, TGFB1, NOS3, and IL9 warrant further investigation. Perspective This article presents results from an association study of 77 polymorphisms, implicated in CVD, and migraine. Variants in TNF, CCR2, TGFB1, NOS3, and IL9 were found to be associated with migraine, but did not remain significant after adjustment for multiple testing. Variations in these genes warrant further investigation. PMID:19559392

  12. 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.

  13. 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.

  14. Polymorphisms of KAP6, KAP7, and KAP8 genes in four Chinese sheep breeds.

    PubMed

    Liu, Y X; Shi, G Q; Wang, H X; Wan, P C; Tang, H; Yang, H; Guan, F

    2014-04-30

    High glycine-tyrosine proteins (HGTPs), also known as keratin-associated proteins (KAPs), play a key role in the major structures and mechanical properties of wool fiber. Sheep HGTPs consist of three multigene families: KAP6, KAP7, and KAP8 genes. Polymorphisms of these three genes have been proposed to have important effects on wool fiber traits. The aim of the present study was to identify polymorphisms of the KAP6, KAP7, and KAP8 genes in four sheep breeds, including Chinese Merino superfine wool sheep, Hu sheep, a Merino x Hu crossed breed, and Romney sheep. Polymerase chain reaction (PCR) product direct sequencing, PCR-single-strand conformation polymorphism, and cloned sequencing methods were used to find genetic variation and identify polymorphisms in these genes. The Mutation Surveyor v3.97 software was used to analyze the sequences. These methods revealed six different sequences of the KAP6 gene, two different sequences of the KAP7 gene, and five different sequences of the KAP8 gene. Accordingly, three (with frequencies>1%) single nucleotide polymorphisms (SNPs) of the KAP6 gene, one SNP of the KAP7 gene, and five SNPs of the KAP8 gene were detected. Interestingly, some of these sequences were present in only certain sheep breeds, thereby suggesting that these special allele sequences could be used as candidate genes of wool characteristics in further studies.

  15. 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…

  16. Further Studies on Gene Polymorphism in the Mainbody and Geographically Isolated Populations of DROSOPHILA PSEUDOOBSCURA

    PubMed Central

    Prakash, Satya

    1977-01-01

    We have examined polymorphism at 22 additional loci in the populations from the mainbody of Drosophila pseudoobscura and an isolated population from Bogotá, Colombia, which also shows partial reproductive isolation from mainbody populations. These studies extend our previous observations of reduced gene polymorphism and apparent lack of unique allele in the Bogotá population. PMID:863242

  17. 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 ...

  18. 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.

  19. 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.

  20. 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

  1. Endothelin-1 gene and endothelial nitric oxide synthase gene polymorphisms in adolescents with juvenile and obesity-associated hypertension.

    PubMed

    Baráth, A; Endreffy, E; Bereczki, Cs; Gellén, B; Szücs, B; Németh, I; Túri, S

    2007-03-01

    Hypertension is an increasing public health problem all over the world. Essential hypertension accounts for more than 90% of cases of hypertension. It is a complex genetic, environmental and demographic trait. New method in molecular biology has been proposed a number of candidate genes, but the linkage or association with hypertension has been problematic (lack of gene-gene and gene-environment interaction). It is well known that genetic influences are more important in younger hypertensives, because children are relatively free from the common environmental factors contributing to essential hypertension. The association studies compare genotype ferquencies of the candidate gene between patient groups and the controls, in pathways known to be involved in blood pressure regulation. This study examined three polymorphisms of these factors encoding genes (ET-1 G+5665T (Lys198Asn), endothelial nitric oxide synthase (eNOS) T-786C promoter polymorphism and 27-bp repeat polymorphism in intron 4) in adolescents with juvenile essential and obesity-associated hypertension. Significant differences were found in the G/T genotype of the ET-1 polymorphism in the hypertensive and obese+hypertensive patients (body mass index (BMI) > 30). A strong association was detected between the BMI and the polymorphism of the ET-1 gene. It seems that ET-1 gene polymorphism plays a role in the development of juvenile hypertension associated with obesity. Although no significant differences were seen in the case of the eNOS promoter polymorphism and the eNOS 4th intron 27-bp repeat polymorphism. It seems that eNOS may play a role, but this is not the main factor in the control of blood pressure; it is rather a fine regulator in this process. This study with adolescents facilitates an understanding of the genetic factors promoting juvenile hypertension and obesity. PMID:17444275

  2. Synergistic effect of LEP and LEPR gene polymorphism on body mass index in a Chinese population.

    PubMed

    Lu, Jin; Zou, Dajin; Zheng, Longyi; Chen, Guangchun; Lu, Jian; Feng, Zhengkang

    2013-12-01

    Both leptin (LEP) and leptin receptor (LEPR) are important in the regulation of body weight. In this study, we evaluated the individual and combined effects of a polymorphic microsatellite marker in the LEP gene 3' flanking region and two polymorphisms (Lys109Arg and Lys656Asn) of the LEPR gene on metabolic markers for obesity in a Chinese population. The genotypes of polymorphisms in LEP and LEPR gene were determined by PCR and SSCP assay in 230 simple obese subjects and 202 control subjects of Chinese population. Logistic regression analysis showed that polymorphism in LEP gene 3' flanking region was associated with waist/hip ratio (WHR) (P = 0.042). Individually, Lys109Arg variant in LEPR gene was associated with systolic blood pressure (P = 0.031) in males, and Lys656Asn variant was associated with serum triglyceride level (P = 0.026). Interestingly, only subjects that simultaneously exhibit all three polymorphisms showed a significantly elevated BMI (29.30 ± 0.85 vs 26.91 ± 1.19, P = 0.037). Taken together, our data suggest that a combination of polymorphism in the LEP gene 3' flanking region, and Lys109Arg, Lys656Asn variants in LEPR gene is associated with obesity in Chinese Han population.

  3. Gene Polymorphisms and Chemotherapy in Non-small Cell Lung Cancer.

    PubMed

    Osawa, Kayo

    2009-08-20

    The phamacogenetics is being used to predict whether the selected chemotherapy will be really effective and tolerable to the patient. Irinotecan, oxidized by CYP3A4 to produce inactive compounds, is used for treatment of various cancers including advanced non small cell lung cancer (NSCLC) patients. CYP3A4(*)16B polymorphism was associated with decreased metabolism of irrinotecan. Irinotecan is also metabolized by carboxylesterase to its principal active metabolite, SN-38, which is subsequently glucuronidated by UGT1As to form the inactive compound SN-38G. UGT1A1(*)28 and UGT1A1(*)6 polymorphisms were useful for predicting severe toxicity with NSCLC patients treated with irinotecan-based chemotherapy. Platinum-based compounds (cisplatin, carboplatin) are being used in combination with new cytotoxic drugs such as gemcitabine, paclitaxel, docetaxel, or vinorelbine in the treatment of advanced NSCLC. Cisplatin activity is mediated through the formation of cisplatin-DNA adducts. Gene polymorphisms of DNA repair factors are therefore obvious candidates for determinants of repair capacity and chemotherapy efficacy. ERCC1, XRCC1 and XRCC3 gene polymorphisms were a useful marker for predicting better survival in advanced NSCLC patients treated with platinum-based chemotherapy. XPA and XPD polymorphisms significantly increased response to platinum-based chemotherapy. These DNA repair gene polymorphisms were useful as a predictor of clinical outcome to the platinum-based chemotherapy. EGFR kinase inhibitors induce dramatic clinical responses in NSCLC patients with advanced disease. EGFR gene polymorphism in intron 1 contains a polymorphic single sequence dinucleotide repeat (CA-SSR) showed a statistically significant correlation with the gefitinib response and was appeared to be a useful predictive marker of the development of clinical outcome containing skin rashes with gefitinib treatment. The other polymorphisms of EGFR were also associated with increased EGFR promoter

  4. 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

  5. Prevalence of coagulase gene polymorphism in Staphylococcus aureus isolates causing bovine mastitis.

    PubMed Central

    Aarestrup, F M; Dangler, C A; Sordillo, L M

    1995-01-01

    This study was conducted to investigate polymorphism of the coagulase gene of Staphylococcus aureus causing bovine mastitis. One hundred eighty-seven strains of S. aureus were isolated from bovine mastitic milk samples obtained from 187 different Danish dairy farms. The isolates were characterised for restriction fragment length polymorphism (RFLP) of the coagulase gene. A variable region of the coagulase gene was amplified using the polymerase chain reaction (PCR) followed by AluI restriction enzyme digestion. A total of 15 different RFLP patterns were observed. The predominant pattern was found in 35% of the isolates. The ease of analysing coagulase gene polymorphisms among a large number of strains, and the multiple distinct polymorphic patterns generated, supports the use of this technique in epidemiological investigations of bovine mastitis. The predominating variants may have predelection for causing intramammary infections. PMID:7648524

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

    PubMed

    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.

  7. Expression of adiponectin and adiponectin receptors 1 and 2 in the porcine uterus, conceptus, and trophoblast during early pregnancy.

    PubMed

    Smolinska, Nina; Maleszka, Anna; Dobrzyn, Kamil; Kiezun, Marta; Szeszko, Karol; Kaminski, Tadeusz

    2014-10-15

    Adiponectin, one of the several adipocytokines secreted mainly by the adipose tissue, plays an important role in regulating energy homeostasis and controls female fertility. Female reproductive functions are closely associated with nutritional status, and adiponectin seems to be an important factor linking the regulation of metabolic homeostasis with reproductive processes. The biological activity of adiponectin is mediated by two distinct receptors, adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2). The objective of this study was to determine the presence of and changes in the gene and protein expression pattern of adiponectin and its receptors in the porcine uterus during early pregnancy and on Days 10 to 11 of the estrous cycle and in the conceptus and trophoblast. The highest level of adiponectin transcript was observed on Days 15 to 16 of gestation, Days 10 to 11 of the cycle in the endometrium, and Days 15 to 16 of gestation in the myometrium. The highest expression of AdipoR1 and AdipoR2 genes was detected on Days 10 to 11 of gestation in the endometrium, and Days 12 to 13 in the myometrium. The highest content of adiponectin protein was noted on Days 12 to 13 and 30 to 32 of gestation in the endometrium and Days 10 to 11 of the cycle in the myometrium. The expression of adiponectin protein was higher on Days 27 to 28 and 30 to 32 in the conceptuses. AdipoR1 protein content in the myometrium was highest on Days 12 to 13 and 30 to 32. In contrast, in the endometrium, it was more constant. The highest content of AdipoR2 protein was detected on Days 15 to 16 and 30 to 32 of gestation, Days 10 to 11 of the cycle in the endometrium, and Days 10 to 11 of gestation in the myometrium. In the conceptuses, the highest AdipoR1 protein content was observed on Days 15 to 16, and the highest AdipoR2 protein expression was determined on Days 15 to 16 and 27 to 28. In the trophoblasts, AdipoR1 protein content was higher on Days 27 to 28 than on Days 30

  8. Role of ADAM33 gene and associated single nucleotide polymorphisms in asthma.

    PubMed

    Sharma, Neeraj; Tripathi, Priya; Awasthi, Shally

    2011-04-01

    Asthma is a multifactorial disorder, primarily resulting from interactions between genetic and environmental factors. ADAM33 gene (located on chromosome 20p13) has been reported to play an important role in asthma. This review article is intended to include all of the publications, to date, which have assessed the association of ADAM33 gene polymorphisms as well as have shown the role of ADAM33 gene in airway remodeling and their expression with asthma. A PubMed search was performed for studies published between 1990 and 2010. The terms "ADAM33," "ADAM33 gene and asthma," and "ADAM33 gene polymorphisms" were used as search criteria. Based on available literature we can only speculate its role in the morphogenesis and functions of the lung. Fourteen studies conducted in different populations were found showing an association of ADAM33 gene polymorphisms with asthma. However, none of the single nucleotide polymorphisms (SNPs) of ADAM33 gene had found association with asthma across all ethnic groups. Because higher expression of ADAM33 is found in the fibroblast and smooth muscle cells of the lung, over- or underexpression of ADAM33 gene may result in alterations in airway remodeling and repair processes. However, no SNP of ADAM33 gene showed significant associations with asthma across all ethnic groups; the causative polymorphism, if any, still has to be identified.

  9. Acute Systemic Inflammation is Unlikely to Affect Adiponectin and Leptin Synthesis in Humans

    PubMed Central

    Ekström, Mattias; Söderberg, Stefan; Tornvall, Per

    2015-01-01

    Adipose tissue (AT), classically thought to be merely an energy store, has been shown to produce inflammatory and metabolically active cytokines. Recently, adiponectin and leptin, adipokines primarily synthesized by adipocytes, have attracted considerable attention because inflammation has been suggested to modulate adipokine levels. However, the regulation of adiponectin and leptin is complex and the knowledge about their synthesis within the early onset of inflammation is poorly understood. The aim of this study was to investigate if the synthesis of adiponectin and leptin is affected during the early phase of an acute systemic inflammation. Eighteen healthy subjects were allocated to vaccination against Salmonella typhi or to a control group, and adiponectin and leptin concentrations measured in plasma during 24 h. Nine patients, without markers of inflammation, undergoing open heart surgery were investigated before and after the operation by analysis of plasma levels and AT gene expression of adiponectin and leptin. Plasma interleukin (IL)-6 concentrations were measured in both cohorts. Plasma levels of IL-6 were doubled after vaccination and increased 30-fold after open heart surgery. Plasma levels of adiponectin and leptin were unchanged after vaccination whereas adiponectin and leptin tended to decrease after surgery. The gene expression of adiponectin and leptin was unaltered in omental and subcutaneous AT after surgery. Despite the use of two models of stimulated in vivo systemic inflammation, we found no evidence of an early regulation of adiponectin and leptin synthesis, indicating that these two adipokines are not key elements in an acute systemic inflammation in humans. PMID:26664879

  10. 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).

  11. 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

  12. 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 ...

  13. Polymorphism and selection in the major histocompatibility complex DRA and DQA genes in the family Equidae.

    PubMed

    Janova, Eva; Matiasovic, Jan; Vahala, Jiri; Vodicka, Roman; Van Dyk, Enette; Horin, Petr

    2009-07-01

    The major histocompatibility complex genes coding for antigen binding and presenting molecules are the most polymorphic genes in the vertebrate genome. We studied the DRA and DQA gene polymorphism of the family Equidae. In addition to 11 previously reported DRA and 24 DQA alleles, six new DRA sequences and 13 new DQA alleles were identified in the genus Equus. Phylogenetic analysis of both DRA and DQA sequences provided evidence for trans-species polymorphism in the family Equidae. The phylogenetic trees differed from species relationships defined by standard taxonomy of Equidae and from trees based on mitochondrial or neutral gene sequence data. Analysis of selection showed differences between the less variable DRA and more variable DQA genes. DRA alleles were more often shared by more species. The DQA sequences analysed showed strong amongst-species positive selection; the selected amino acid positions mostly corresponded to selected positions in rodent and human DQA genes.

  14. 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

  15. Association of oestrogen receptor gene polymorphism with the long-term results of rotational acetabular osteotomy.

    PubMed

    Yamanaka, Makoto; Ishijima, Muneaki; Tokita, Akifumi; Sakamoto, Yuko; Kaneko, Haruka; Maezawa, Katsuhiko; Nozawa, Masahiko; Kurosawa, Hisashi

    2009-08-01

    Acetabular dysplasia (AD) contributes to the development of osteoarthritis of the hip. A rotational acetabular osteotomy (RAO) is one of the methods of pelvic osteotomy to prevent or treat secondary osteoarthritis of the hip. Although most of the patients that undergo RAO show satisfactory results, some have poor results. This study investigated whether gene polymorphisms of both the vitamin D receptor (VDR) and oestrogen receptor (ER) are involved in both AD and the postoperative results following RAOs. Sixty-four Japanese patients with AD who were treated by an RAO were enrolled in this study (59 women and 5 men, aged 13-59, with an average age of 40.3). Gene polymorphisms of the VDR [ApaI and TaqI restriction fragment length polymorphisms (RFLPs)] and ER (PvuII and XbaI RFLPs) were determined in these patients. The relationship between both the AD and radiographic postoperative changes of the hip joint after an RAO with these gene polymorphisms were examined. The frequencies of ER gene polymorphism coded as pp (RFLP/PvuII) in patients with AD were statistically significantly different (p = .011) from those coded as both PP and Pp. The joint space width narrowed even after RAO in 90% of the patients with the pp gene polymorphism, while it narrowed in only 35% of the patients with either PP or Pp seven years or longer after an RAO. The PvuII polymorphism in the ER gene was associated with the postoperative result of an RAO, while no association was observed between the AD with VDR and ER gene polymorphisms.

  16. Expression of adiponectin and adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) in the porcine uterus during the oestrous cycle.

    PubMed

    Smolinska, Nina; Dobrzyn, Kamil; Maleszka, Anna; Kiezun, Marta; Szeszko, Karol; Kaminski, Tadeusz

    2014-04-01

    Adiponectin is a hormone secreted primarily by white adipose tissue. Recent studies have shown that adiponectin and its receptors (AdipoR1 and AdipoR2) are expressed in different reproductive tissues, including the ovary and uterus. This newly discovered endocrine system plays an important role in the regulation of reproductive processes. The expression of the adiponectin system in the porcine uterus during the oestrous cycle has not been researched to date. The aim of the present study was to investigate the presence and changes in adiponectin system expression in the porcine uterus on days 2-3, 10-12, 14-16, and 17-19 of the oestrous cycle. The expression of the adiponectin gene was highest on days 14-16 and 2-3 in the endometrium and myometrium, respectively. In the endometrium, the content of AdipoR1 and AdipoR2 mRNAs was highest on days 10-12, whereas significantly higher expression levels of both genes were noted in the myometrium on days 17-19. The highest content of adiponectin and AdipoR1 protein in the endometrium was reported on days 2-3. In the myometrium, the expression levels of both receptor proteins were significantly higher on days 17-19. Adiponectin system proteins were localized in endometrial epithelial glandular cells, luminal epithelial cells and stromal cells as well as in longitudinal and circular muscles of the myometrium. This study demonstrated the presence of adiponectin, AdipoR1 and AdipoR2 genes and proteins in the porcine uterus and the effect of the stage of the oestrous cycle on the expression of the adiponectin system. Our results suggest that locally synthesized adiponectin directly affects uterine functions.

  17. 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

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

    PubMed Central

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

    2014-01-01

    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 7days) 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

  19. 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

  20. 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.

  1. 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: A Prospective Case-Control Study in a Romanian Population-The Nutrichild Study.

    PubMed

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

    2016-03-01

    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.

  2. 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

  3. TATA box polymorphisms in human gene promoters and associated hereditary pathologies.

    PubMed

    Savinkova, L K; Ponomarenko, M P; Ponomarenko, P M; Drachkova, I A; Lysova, M V; Arshinova, T V; Kolchanov, N A

    2009-02-01

    TATA-binding protein (TBP) is the first basal factor that recognizes and binds a TATA box on TATA-containing gene promoters transcribed by RNA polymerase II. Data available in the literature are indicative of admissible variability of the TATA box. The TATA box flanking sequences can influence TBP affinity as well as the level of basal and activated transcription. The possibility of mediated involvement in in vivo gene expression regulation of the TBP interactions with variant TATA boxes is supported by data on TATA box polymorphisms and associated human hereditary pathologies. A table containing data on TATA element polymorphisms in human gene promoters (about 40 mutations have been described), associated with particular pathologies, their short functional characteristics, and manifestation mechanisms of TATA-box SNPs is presented. Four classes of polymorphisms are considered: TATA box polymorphisms that weaken and enhance promoter, polymorphisms causing TATA box emergence and disappearance, and human virus TATA box polymorphisms. The described examples are indicative of the polymorphism-associated severe pathologies like thalassemia, the increased risk of hepatocellular carcinoma, sensitivity to H. pylori infection, oral cavity and lung cancers, arterial hypertension, etc. PMID:19267666

  4. 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

  5. Association between osteoprotegerin gene polymorphisms and cardiovascular disease in type 2 diabetic patients

    PubMed Central

    Guo, Changlei; Hu, Fudong; Zhang, Shaoli; Wang, Yakun; Liu, Hengdao

    2013-01-01

    Osteoprotegerin (OPG) gene polymorphisms (T245G, T950C and G1181C) have been associated with osteoporosis and early predictors of cardiovascular disease. The aim of this study was to evaluate whether these polymorphisms contribute to cardiovascular disease (CVD) in type 2 diabetic patients. We performed a case-control study with 178 CVD subjects with diabetes and 312 diabetic patients without CVD to assess the impact of variants of the OPG gene on the risk of CVD. The OPG gene polymorphisms were analyzed by using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). There was no significant association between the T245G and G1181C polymorphisms and CVD in the additive genetic model (OR = 0.96, 95% CI 0.64–1.45, p = 0.79; OR = 1.06, 95% CI 0.81–1.39, p = 0.65, respectively). However, the C allele of the T950C polymorphism was independently associated with a risk of CVD in type 2 diabetic patients in this genetic model (OR = 1.38, 95% CI 1.07–1.80, p = 0.01). This study provides evidence that the C allele of the T950C polymorphism is associated with increased risk of CVD in diabetic patients. However, well-designed prospective studies with a larger sample size are needed to validate these results. PMID:23885198

  6. [The role of FTO gene polymorphism in the pathogenesis of obesity].

    PubMed

    Tercjak, Magdalena; Luczyński, Włodzimierz; Wawrusiewicz-Kurylonek, Natalia; Bossowski, Artur

    2010-01-01

    Both environmental and genetic factors play a role in the pathogenesis of obesity. At present, researchers are examining the genetic background of overweight. Over 100 genes are suspected to influence the obesity. One of those genes is FTO (fat mass and obesity-associated gene). In the manuscript, the relationship between FTO gene polymorphism (AA allele) and overweight, obesity and their consequences are discussed. It was proved, in studies on large number of people, that FTO gene polymorphism is related to higher body mass index, weight and abdominal circumference. Some authors showed that FTO gene polymorphism influences the food intake, energy expanditure and insulin resistance. The expression of FTO gene product was noticed in both, the peripheral as well as central nervous system (hypothalamus). It is possible that FTO gene product is involved in the DNA and RNA reparation and other metabolic processes, however, its function is not yet clear. The assessment of FTO gene polymorphism can allow us to separate patients with the tendency for higher weight. The elucidation of the role of FTO in the pathogenesis of obesity can result in the development of new therapeutic options for this epidemic of XXI century.

  7. [The role of FTO gene polymorphism in the pathogenesis of obesity].

    PubMed

    Tercjak, Magdalena; Luczyński, Włodzimierz; Wawrusiewicz-Kurylonek, Natalia; Bossowski, Artur

    2010-01-01

    Both environmental and genetic factors play a role in the pathogenesis of obesity. At present, researchers are examining the genetic background of overweight. Over 100 genes are suspected to influence the obesity. One of those genes is FTO (fat mass and obesity-associated gene). In the manuscript, the relationship between FTO gene polymorphism (AA allele) and overweight, obesity and their consequences are discussed. It was proved, in studies on large number of people, that FTO gene polymorphism is related to higher body mass index, weight and abdominal circumference. Some authors showed that FTO gene polymorphism influences the food intake, energy expanditure and insulin resistance. The expression of FTO gene product was noticed in both, the peripheral as well as central nervous system (hypothalamus). It is possible that FTO gene product is involved in the DNA and RNA reparation and other metabolic processes, however, its function is not yet clear. The assessment of FTO gene polymorphism can allow us to separate patients with the tendency for higher weight. The elucidation of the role of FTO in the pathogenesis of obesity can result in the development of new therapeutic options for this epidemic of XXI century. PMID:20813088

  8. A single nucleotide polymorphism in ADIPOQ predicts biochemical recurrence after radical prostatectomy in localized prostate cancer

    PubMed Central

    Zhang, Guiming; Sun, LiJiang; Zhu, Yao; Ye, Dingwei

    2015-01-01

    Adiponectin has been implicated in prostate cancer (PCa) aggressiveness. However, the role of genetic variations in the adiponectin (ADIPOQ) gene in PCa progression remains unknown. To determine whether genetic variants in ADIPOQ are associated with the risk of biochemical recurrence (BCR) after radical prostatectomy (RP). We evaluated three common ADIPOQ polymorphisms in 728 men with clinically localized PCa who underwent RP. Multivariable Cox proportional hazards models and Kaplan–Meier analysis were used to assess their prognostic significance on BCR. The plasma adiponectin concentrations were measured by enzyme-linked immunosorbent assay. ADIPOQ rs182052 variant allele was associated with both increased risk of BCR [HR: 2.44; 95% confidence interval (CI): 1.57–3.79, P = 6×10−5] and decreased adiponectin level (β = −0.048, P = 0.004). Stratified analyses demonstrated that the association was more pronounced in men with higher visceral adipose tissue. Our data support that the ADIPOQ rs182052 SNP may be a predictive biomarker for BCR after RP by a possible mechanism of altering the adiponectin level. If validated, genetic predictors of outcome may help individualizing treatment for PCa. PMID:26320190

  9. A single nucleotide polymorphism in ADIPOQ predicts biochemical recurrence after radical prostatectomy in localized prostate cancer.

    PubMed

    Gu, Chengyuan; Qu, Yuanyuan; Zhang, Guiming; Sun, LiJiang; Zhu, Yao; Ye, Dingwei

    2015-10-13

    Adiponectin has been implicated in prostate cancer (PCa) aggressiveness. However, the role of genetic variations in the adiponectin (ADIPOQ) gene in PCa progression remains unknown. To determine whether genetic variants in ADIPOQ are associated with the risk of biochemical recurrence (BCR) after radical prostatectomy (RP). We evaluated three common ADIPOQ polymorphisms in 728 men with clinically localized PCa who underwent RP. Multivariable Cox proportional hazards models and Kaplan-Meier analysis were used to assess their prognostic significance on BCR. The plasma adiponectin concentrations were measured by enzyme-linked immunosorbent assay. ADIPOQ rs182052 variant allele was associated with both increased risk of BCR [HR: 2.44; 95% confidence interval (CI): 1.57-;3.79, P = 6×10-5] and decreased adiponectin level (β = -0.048, P = 0.004). Stratified analyses demonstrated that the association was more pronounced in men with higher visceral adipose tissue. Our data support that the ADIPOQ rs182052 SNP may be a predictive biomarker for BCR after RP by a possible mechanism of altering the adiponectin level. If validated, genetic predictors of outcome may help individualizing treatment for PCa.

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

    PubMed

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

    2014-08-01

    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.

  11. 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

  12. 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

  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. Comparative analysis of IL6 and IL6 receptor gene polymorphisms in mastocytosis.

    PubMed

    Rausz, Eszter; Szilágyi, Agnes; Nedoszytko, Boguslaw; Lange, Magdalena; Niedoszytko, Marek; Lautner-Csorba, Orsolya; Falus, András; Aladzsity, István; Kokai, Márta; Valent, Peter; Marschalko, Márta; Hidvégi, Bernadett; Szakonyi, József; Csomor, Judit; Várkonyi, Judit

    2013-01-01

    Mastocytosis is a rare disease with reported high interleukin-6 (IL6) levels influencing disease severity. The present study investigated polymorphisms within the genes that encode IL6 and its receptor (IL6R) in relation to mastocytosis development in a case-control design. Analysis of the IL6R Asp358Ala polymorphism showed that carriers of the AA genotype had a 2·5-fold lower risk for mastocytosis than those with the AC or CC genotypes. No association with mastocytosis was found for the IL6-174G/C polymorphism, however, it may influence the effect of IL6R polymorphism. To the best of our knowledge this is the first study analysing IL6/IL6R polymorphisms in mastocytosis.

  15. 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.

  16. 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

  17. The effect of polymorphisms in candidate genes on the long-term risk of lipodystrophy and dyslipidemia in HIV-infected white patients starting antiretroviral therapy.

    PubMed

    Marzocchetti, Angela; Schwarz, Jessica; Di Giambenedetto, Simona; Colafigli, Manuela; Bracciale, Laura; Fabbiani, Massimilliano; Fantoni, Massimo; Trecarichi, Enrico; Cauda, Roberto; De Luca, Andrea

    2011-12-01

    We investigated whether polymorphisms in human candidate genes could be associated with a different risk of developing lipodystrophy and dyslipidemia in HIV-infected patients starting combination antiretroviral therapy (cART). Genomic DNA samples from white HIV-1-infected patients were analyzed for seven polymorphisms located in the MDR1, TNF-α, APM1, APOE, and LPL genes. Lipid data were retrospectively collected beginning with the initiation of cART. Lipodystrophy was assessed cross-sectionally and then prospectively. The association with lipodystrophy and National Cholesterol Evaluation Program Adult Treatment Panel III-defined lipid thresholds was analyzed using survival analysis and logistic regression. One-hundred and seventy-four patients were genotyped. In 151 patients assessed for lipodystrophy, MDR1 3435 T homozygosis was associated with a higher hazard (adjusted hazard ratio, aHR, versus CT 0.25; p=0.02) and tumor necrosis factor (TNF)-α 308 G homozygosis with a lower hazard (vs. AA aHR 2.14; p=0.04) of developing trunk fat accumulation after adjusting for gender and initial cART type. The TNF 238 GG genotype was associated with a higher risk of developing low HDL-cholesterol levels (adjusted odd ratio, aOR, 5.91; p=0.01) while patients carrying the LPL S477X mutation were at lower risk of reaching high non-HDL-cholesterol levels (aOR 0.39; p=0.05). The APOEe3/3 genotype patients were at lower risk (aOR 0.26, p=0.015), whereas the adiponectin 276 GT carriers were at higher risk of developing hypertriglyceremia (vs. GG aOR 3.10; p=0.04). Knowledge of the effect of genetic determinants on dyslipidemia and lipodystrophy may prompt the investigation of potential pathogenetic mechanisms and might eventually be used for guiding individualized treatment decisions.

  18. Association of vitamin D receptor gene polymorphisms and Parkinson's disease in Hungarians.

    PubMed

    Török, Rita; Török, Nora; Szalardy, Levente; Plangar, Imola; Szolnoki, Zoltan; Somogyvari, Ferenc; Vecsei, Laszlo; Klivenyi, Peter

    2013-09-13

    Vitamin D receptor (VDR) gene encodes a transcription factor that influences calcium homeostasis and immunoregulation, and may play a role in neurological disorders including Parkinson's disease (PD). The investigations of the association between VDR and PD in different populations revealed various results. In a present study 100 PD patients and 109 healthy controls from the Hungarian population were genotyped for four polymorphic sites (BsmI, ApaI, FokI and TaqI) in the VDR gene. The polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Our results demonstrate an association between the FokI C allele and PD; the frequency of the C allele was significantly higher in PD patients than in controls, suggesting that this polymorphism may have a role in the development of PD in these patients.

  19. [Polymorphism of connexin 40 gene-- a novel genetic marker of the sick sinus node syndrome].

    PubMed

    Chernova, A A; Nikulina, S Iu; Shul'man, V A; Kukushkina, T S; Voevoda, M I; Maksimov, V N

    2011-01-01

    In this work we have demonstrated for the first time on the clinico-genetic material association between hereditary sick sinus node syndrome and connexin 40 gene polymorphism. We have revealed that heterozygous variant of connexin 40 gene variant is more frequent among patients with sick sinus node syndrome and their healthy relatives than in persons of control group.

  20. Interleukin-2 and interleukin-6 gene promoter polymorphisms, and early failure of dental implants.

    PubMed

    Campos, Maria Isabela Guimarães; Godoy dos Santos, Maria Cristina Leme; Trevilatto, Paula Cristina; Scarel-Caminaga, Raquel Mantuaneli; Bezerra, Fabio Jose; Line, Sergio Roberto Peres

    2005-12-01

    Single nucleotide polymorphisms in the promoter region of the human interleukin (IL)-2 (T-330G) and IL-6 (G-174C) genes have modified the transcriptional activity of these cytokines and are associated with several diseases. The aim of this study was to investigate the possible relationship between these single nucleotide polymorphisms and early implant failure. A sample of 74 nonsmokers was divided into 2 groups: test group comprising 34 patients (mean age 49.3 years) with >or=1 implants that failed and control group consisting of 40 patients (mean age 43.8 years) with >or=1 healthy implants. Genomic deoxyribonucleic acid from oral mucosa was amplified by polymerase chain reaction and analyzed by restriction fragment length polymorphism. Monte Carlo simulations (P < 0.05) were used to assess differences in allele and genotypes frequencies of the single nucleotide polymorphisms between the 2 groups. No significant differences were observed in the allele and genotypes distribution of both polymorphisms when the 2 groups were compared. The results indicate that polymorphisms in the IL-2 (T-330G) and IL-6 (G-174C) genes are not associated with early implant failure, suggesting that the presence of those single nucleotide polymorphisms does not constitute a genetic risk factor for implant loss in the studied population. PMID:16361891

  1. Association of XPC Gene Polymorphisms with Susceptibility to Prostate Cancer: Evidence from 3,936 Subjects

    PubMed Central

    Zou, Yan-Feng; Tao, Jin-Hui; Ye, Qian-Ling; Pan, Hai-Feng; Pan, Fa-Ming; Su, Hong

    2013-01-01

    Aim: Polymorphisms of xeroderma pigmentosum complementation group C (XPC) are thought to have significant effects on prostate cancer (PCa) risk. The aim of our study was to evaluate the impact of XPC gene polymorphisms on PCa risk by using a meta-analysis. Methods: Data were collected from the following electronic databases: PubMed, EMBASE, Elsevier Science Direct, Cochrane Library, and CNKI, with the last report up to April 30, 2013. Odds ratios with 95% confidence intervals were used to assess the strength of the association. Results: A total of five separate case–control studies (1966 cases and 1970 controls) were included in this meta-analysis. Meta-analysis was performed for the rs2228001 and PAT+/−polymorphisms. We did not detect a significant association between rs2228001 polymorphism and PCa (p>0.05). Similar results were found in stratification analyses by ethnicity and tumor stage. We detected a significant association of PAT+/−polymorphism with PCa (p<0.05). In stratification analysis, we did not detect a significant association of PAT+/−polymorphism with risk of bone metastasis in PCa patients (p>0.05). Conclusion: These analyses suggest that XPC gene PAT+/−polymorphism, but not rs2228001, likely contributes to susceptibility to PCa. PMID:24093803

  2. Is catechol-o-methyltransferase gene polymorphism a risk factor in the development of premenstrual syndrome?

    PubMed Central

    Deveci, Esma Ozturk; Selek, Salih; Camuzcuoglu, Aysun; Hilali, Nese Gul; Camuzcuoglu, Hakan; Erdal, Mehmet Emin; Vural, Mehmet

    2014-01-01

    Objective The objective of this study was to investigate whether there was a correlation between catechol-o-methyltransferase (COMT) gene polymorphism, which is believed to play a role in the etiology of psychotic disorders, and premenstrual syndrome (PMS). Methods Fifty-three women with regular menstrual cycles, aged between 18 and 46 years and diagnosed with PMS according to the American Congress of Obstetrics and Gynecology criteria were included in this study as the study group, and 53 healthy women having no health problems were selected as the controls. Venous blood was collected from all patients included in the study and kept at -18℃ prior to analysis. Results There was no significant difference between the groups in terms of demographic features such as age, body mass index, number of pregnancies, parity, and number of children. No statistically significant difference was observed in terms of COMT gene polymorphism (p=0.61) between women in the PMS and the control groups. However, a significant difference was found between arthralgia, which is an indicator of PMS, and low-enzyme activity COMT gene (Met/Met) polymorphism (p=0.04). Conclusion These results suggested that there was no significant relationship between PMS and COMT gene polymorphism. Since we could not find a direct correlation between the COMT gene polymorphism and PMS, further studies including alternative neurotransmitter pathways are needed to find an effective treatment for this disease. PMID:25045629

  3. 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

  4. Effects of interleukin (IL)-6 gene polymorphisms on recurrent aphthous stomatitis.

    PubMed

    Karakus, Nevin; Yigit, Serbulent; Rustemoglu, Aydin; Kalkan, Goknur; Bozkurt, Nihan

    2014-03-01

    Recurrent aphthous stomatitis (RAS) is a common disease with oral ulceration in which cytokines are thought to play an important role. High levels of interleukin (IL)-6, a pro-inflammatory cytokine have been detected in the circulation of ulcer tissue. The purpose of the present study was to investigate if the IL-6 gene polymorphisms are associated with RAS or clinical characteristics of RAS in a cohort of Turkish population. 184 RAS patients and 150 healthy controls were included in the study. The genotypes of IL-6 gene -572G>C and -174G>C polymorphisms were determined using polymerase chain reaction based restriction fragment length polymorphism analysis. The genotype frequencies of -572G>C polymorphism showed statistically significant differences between RAS patients and controls (p = 0.01). Frequencies of GG + GC genotypes and G allele of -572G>C polymorphism were found higher in RAS patients (p = 0.0001, OR 10.8, 95 % CI 2.79-70.5; p = 0.0008, OR 2.06, 95 % CI 1.35-3.17, respectively). The genotype frequencies of -174G>C polymorphism also showed statistically significant differences between RAS patients and controls (p < 0.0001). Frequencies of GG genotype and G allele of -174G>C polymorphism were found higher in RAS patients (p < 0.0001, OR 4.87, 95 % CI 3.06-7.85; p < 0.0001, OR 3.82, 95 % CI 2.64-5.59, respectively). GG-GG combined genotype and G-G haplotype of -174G>C to -572G>C loci were also significantly higher in RAS patients (p < 0.0001 and p = 1.5 × 10(-8), respectively). After stratifying clinical and demographical characteristics of RAS patients according to IL-6 gene polymorphisms, an association was observed between family history of RAS and -174G>C polymorphism (p = 0.011). Susceptibility effects of both IL-6 gene -572G>C and -174G>C polymorphisms for RAS were observed. Further studies are necessary to prove the association of IL-6 gene polymorphisms with RAS.

  5. Investigation on estrogen receptor alpha gene polymorphisms in Iranian women with recurrent pregnancy loss

    PubMed Central

    Mahdavipour, Marzieh; Idali, Farah; Zarei, Saeed; Talebi, Saeed; Fatemi, Ramina; Jeddi-Tehrani, Mahmood; Pahlavan, Somayeh; Rajaei, Farzad

    2014-01-01

    Background: Recurrent pregnancy loss (RPL) is a multifactorial disorder. Environmental factors and genetics can affect pregnancy outcomes. Objective: Conflicting data suggest an association between estrogen receptor alpha (ESR1) gene polymorphisms and RPL. In this study, such association was investigated in Iranian women with RPL. Materials and Methods: In this case control study, blood samples were collected from 244 women with a history of three or more consecutive pregnancy losses and 104 healthy women with at least two live births. Using polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP), we studied -397C/T and -351A/G polymorphisms on ESR1 gene in case and control subjects. Results: The genotypic frequencies of -397C/T and -351A/G polymorphisms on ESR1were not significantly different between RPL and control groups (p=0.20 and p=0.09, respectively). A significantly negative correlation was observed between -397C/T and -351A/G (r=-0.852, p<0.001) in RPL women and complete linkage disequilibrium between the investigated polymorphisms was found (D’: 0.959; r-square= 0.758, p<0.001). Conclusion: This investigation suggests that the analyzed polymorphisms on ESR1gene are not associated with an increased risk of RPL in the studied population. PMID:25071847

  6. TNFA and IL10 Gene Polymorphisms are not Associated with Periodontitis in Brazilians

    PubMed Central

    Moreira, P. R; Costa, J. E; Gomez, R. S; Gollob, K. J; Dutra, W. O

    2009-01-01

    IL-10 and TNF-α are cytokines that have complex and opposing roles in the inflammatory responses. G/A polymorphisms at position –1082 of IL10 and –308 of TNFA genes have been reported to influence the expression of IL-10 and TNF-α, respectively. The aim of this study was to investigate the association between the IL10 (-1082) and TNFA (- 308) gene polymorphisms with different clinical forms or severity of periodontitis in a sample of Brazilian individuals. DNA was obtained from oral swabs of 165 Brazilian individuals, which were divided into three groups: individuals with chronic periodontitis, aggressive periodontitis and individuals without clinical evidence of periodontitis. Evaluation of IL10 and TNFA polymorphisms was performed by RFLP analysis. Statistical analysis of data was performed using the χ2 likelihood ratio and Fisher`s exact test. No significant differences in the genotype and allele distribution of either IL10 or TNFA were observed among individuals with different clinical forms or with different degrees of severity of periodontitis. Moreover, combined analysis of IL10 and TNFA polymorphisms did not show any association with periodontal status. As conclusion, the IL10 and TNFA gene promoter polymorphisms investigated are not associated with different clinical forms of periodontitis or with severity of the disease in the Brazilian population polymorphisms. PMID:19771178

  7. NO ASSOCIATION BETWEEN tHbmass AND POLYMORPHISMS IN THE HBB GENE IN ENDURANCE ATHLETES.

    PubMed

    Malczewska-Lenczowska, J; Orysiak, J; Majorczyk, E; Pokrywka, A; Kaczmarski, J; Szygula, Z; Sitkowski, D

    2014-06-01

    The aim of this study was to examine the association between tHbmass and HBB gene polymorphisms in athletes of endurance disciplines. Eighty-two well-trained athletes (female n=36, male n=46), aged 19.3 ± 2.7 years, representing cross country skiing (n=37) and middle- and long-distance running (n=45), participated in the study. Genotyping for 2 polymorphisms in the HBB gene (- 551C/T and intron 2, +16 C/G) was performed using restriction fragment length polymorphism analysis. Total haemoglobin mass (tHbmass) was determined by the optimized carbon monoxide rebreathing method. Blood morphology, indices of iron status (ferritin, transferrin receptor and total iron binding capacity) and C reactive protein were also determined. No differences were found in the HBB genotype and allele frequencies between male and female athletes. Regardless of the polymorphisms, no relationships were found between HBB genotypes as well as alleles and relative values of tHbmass, expressed per body mass (g · kg(-1) BM), both in female and male athletes. Our results demonstrated that -551 C/T and intron 2, +16 C/G polymorphisms of the HBB gene have no association with total haemoglobin mass in endurance athletes. It cannot be ruled out that several polymorphisms, each with a small but significant contribution, may be responsible for the amount of haemoglobin.

  8. NO ASSOCIATION BETWEEN tHbmass AND POLYMORPHISMS IN THE HBB GENE IN ENDURANCE ATHLETES

    PubMed Central

    Malczewska-Lenczowska, J.; Orysiak, J.; Majorczyk, E.; Pokrywka, A.; Kaczmarski, J.; Szygula, Z.

    2014-01-01

    The aim of this study was to examine the association between tHbmass and HBB gene polymorphisms in athletes of endurance disciplines. Eighty-two well-trained athletes (female n=36, male n=46), aged 19.3 ± 2.7 years, representing cross country skiing (n=37) and middle- and long-distance running (n=45), participated in the study. Genotyping for 2 polymorphisms in the HBB gene (- 551C/T and intron 2, +16 C/G) was performed using restriction fragment length polymorphism analysis. Total haemoglobin mass (tHbmass) was determined by the optimized carbon monoxide rebreathing method. Blood morphology, indices of iron status (ferritin, transferrin receptor and total iron binding capacity) and C reactive protein were also determined. No differences were found in the HBB genotype and allele frequencies between male and female athletes. Regardless of the polymorphisms, no relationships were found between HBB genotypes as well as alleles and relative values of tHbmass, expressed per body mass (g · kg-1 BM), both in female and male athletes. Our results demonstrated that -551 C/T and intron 2, +16 C/G polymorphisms of the HBB gene have no association with total haemoglobin mass in endurance athletes. It cannot be ruled out that several polymorphisms, each with a small but significant contribution, may be responsible for the amount of haemoglobin. PMID:24899775

  9. 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

  10. Correlation of genetic polymorphism of vascular endothelial growth factor gene with susceptibility to lung cancer.

    PubMed

    Liu, C; Zhou, X; Gao, F; Qi, Z; Zhang, Z; Guo, Y

    2015-06-01

    The aim of the study is to study the correlation of genetic polymorphism of vascular endothelial growth factor (VEGF) gene with susceptibility to primary lung cancer. A total of 414 patients with primary lung cancer and 338 healthy volunteers were enrolled in this case-control study from September 2008 to October 2011. Gene identification with PCR-RFLP (polymerase chain reaction-based restriction fragment length polymorphism) was used to detect in white blood cells from the subjects the single-nucleotide polymorphisms (SNP) of VEGF gene, including +405G/C, -460 T/C, -1154G/A, -2578C/A sites. Association of genotypes or haplotypes with susceptibility of lung cancer was analyzed with unconditional logistic regression adjusted by gender and age. Smoking was significantly associated with increased risk of lung cancer. Gene phenotypic analysis demonstrated that C allele of +405G/C in VEGF gene was significantly associated increased risk of lung cancer in males (P=0.0094, odds ratio=1.634.3), as that with carrying GCTC haplotype (odds ratio=1.349), whereas carrying GACG had decreased risk for lung cancer (odds ratio=0.044). No relationship existed between 460 T/C, -1154G/A, -2578C/A alleles of VEGF gene and risk of lung cancer. VEGF gene polymorphism may have a role in the development of lung cancer.

  11. Gene expression of adiponectin receptors in human visceral and subcutaneous adipose tissue is related to insulin resistance and metabolic parameters and is altered in response to physical training

    PubMed Central

    Blüher, Matthias; Williams, Catherine J.; Klöting, Nora; Hsi, Alex; Ruschke, Karen; Oberbach, Andreas; Fasshauer, Mathias; Berndt, Janin; Schön, Michael R.; Wolk, Alicja; Stumvoll, Michael; Mantzoros, Christos S.

    2009-01-01

    Objective Adiponectin receptors 1 and 2 (AdipoR1/R2) mediate the effects of adiponectin on glucose and lipid metabolism in vivo. We examined whether AdipoR1 and/or AdipoR2 mRNA expression in human adipose tissue is fat-depot specific. We also studied whether their expression in visceral and subcutaneous fat depots is associated with metabolic parameters and whether their expression is regulated by intensive physical exercise. Research design and methods We determined metabolic parameters and assessed AdipoR1 and R2 mRNA expression using quantitative real-time PCR in adipose tissue in an observational study of 153 subjects, and an interventional study of 60 subjects (20 each with normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes) before and after intensive physical training for 4 weeks. Results AdipoR1 and R2 mRNA expression is not significantly different between omental and subcutaneous fat, but their expression is several fold lower in adipose tissue than in muscle. AdipoR2 mRNA expression in visceral fat is highly correlated with its expression in subcutaneous fat. AdipoR2 mRNA expression in both visceral and subcutaneous fat is positively associated with circulating adiponectin and HDL levels but negatively associated with obesity as well as parameters of insulin resistance, glycemia and other lipid levels before and after adjustment for fat mass. Physical training for 4 weeks resulted in increased AdipoR1 and AdipoR2 mRNA expression in subcutaneous fat. Conclusions AdipoR2 mRNA expression in fat is negatively associated with insulin resistance and metabolic parameters independently of obesity, and may mediate the improvement of insulin resistance in response to exercise. PMID:17878241

  12. Association of Tumor Necrosis Factor Alpha Gene Polymorphisms with Inflammatory Bowel Disease in Iran

    PubMed Central

    NADERI, Nosratollah; FARNOOD, Alma; DADAEI, Tahereh; HABIBI, Manijeh; BALAII, Hedie; FIROUZI, Farzad; MAHBAN, Aydin; SOLTANI, Masoumeh; ZALI, Mohammadreza

    2014-01-01

    Abstract Background Inflammatory bowel disease (IBD) is a chronic disease of unknown etiology, in which genetic factors, seem to play an important role in the disease predisposition and course. Assessment of tumor necrosis factor (TNF-α) gene polymorphisms in many populations showed a possible association with IBD. Considering the genetic variety in different ethnic groups, the aim of the present study was to investigate the association of five important single nucleo-tide polymorphisms (SNPs) in the promoter region of (TNF-α) gene with IBD in Iran. Methods In this case-control study, 156 Ulcerative colitis (UC) patients, 50 Crohn’s disease (CD) patients and 200 sex and age matched healthy controls of Iranian origin were enrolled. The study was performed during a two year period (2008–2010) at Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. DNA samples were evaluated for (TNF-α) gene polymorphisms (including -1031, -863, -857, -308 and -238) by PCR and RFLP methods. Results The frequency of the mutant allele of -1031 polymorphism was significantly higher in Iranian patients with Crohn’s disease compared to healthy controls (P=0.01, OR=1.92; 95% CI: 1.14-3.23). None of the other evaluated polymorphisms demonstrated a significant higher frequency of mutant alleles in Iranian IBD patients compared to controls. Conclusion Among the five assessed (SNPs), only -1031 polymorphism of (TNF-α) gene may play a role in disease susceptibility for Crohn’s disease in Iran. This pattern of distribution of (TNF-α) gene polymorphisms could be specific in this population. PMID:26060764

  13. Apolipoprotein gene polymorphisms and plasma levels in healthy Tunisians and patients with coronary artery disease

    PubMed Central

    Bahri, Raoudha; Esteban, Esther; Moral, Pedro; Hassine, Mohsen; Hamda, Khaldoun Ben; Chaabani, Hassen

    2008-01-01

    Aim To analyze apolipoprotein gene polymorphisms in the Tunisian population and to check the relation of these polymorphisms and homocysteine, lipid and apolipoprotein levels to the coronary artery disease (CAD). Methods In healthy blood donors and in patients with CAD complicated by myocardial infarction (MI) four apolipoprotein gene polymorphisms [APO (a) PNR, APO E, APO CI and APO CII] were determined and plasma levels of total homocysteine, total cholesterol (TC), triglycerides (TG), HDL-cholesterol (HLD-C) and apolipoproteins (apo A-I, Apo B, Apo E) were measured. Results Analysis of the four apolipoprotein gene polymorphisms shows a relative genetic homogeneity between Tunisian population and those on the other side of Mediterranean basin. Compared to controls, CAD patients have significantly higher main concentrations of TC, TG, LDL-C, apo B and homocysteine, and significantly lower ones of HDL-C, apo A-I and apo E. The four apolipoprotein gene polymorphisms have not showed any significant differences between patients and controls. However, the APO E4 allele appears to be associated to the severity of CAD and to high levels of atherogenic parameters and low level of apo E, which has very likely an anti-atherogenic role. Conclusion Although APO (a) PNR, APO CI and APO CII genes are analyzed in only few populations, they show a frequency distribution, which is not at variance with that of APO E gene and other widely studied genetic markers. In the Tunisian population the APO E 4 appears to be only indirectly involved in the severity of CAD. In the routine practice, in addition of classic parameters, it will be useful to measure the concentration of apo E and that of Homocysteine and if possible to determine the APO E gene polymorphism. PMID:19014618

  14. EVC gene polymorphisms and risks of isolated hypospadias – a preliminary study

    PubMed Central

    Kowal, Andrzej; Mostowska, Adrianna; Mydlak, Dariusz; Eberdt-Gołąbek, Bożena; Misztal, Matthew; Jagodziński, Paweł P.

    2015-01-01

    Introduction Hypospadias has a complex etiology with both genetic and environmental factors contributing to the condition. Urogenital abnormalities including hypospadias, are found in 22% of cases with Ellis van Creveld syndrome (EvC). Mutations in the EVC gene can cause major and minor anomalies, which form phenotypes that partially overlap with those present in EvC. The aim of this study was to evaluate the association between nucleotide variants of the EVC gene and the risk of hypospadias. Material and methods Four single nucleotide polymorphisms (SNPs) of the EVC gene (rs3774856, rs2302075, rs1383180, rs7680768) were taken under investigation in 96 patients with isolated hypospadias and 284 matched controls. Genotyping of all polymorphisms was carried out by PCR and followed by appropriate restriction enzyme digestion (PCR-RFLP). Results Individuals homozygous for the SNP rs2302075 (p.Thr449Lys) showed an elevated risk for hypospadias. Haplotypes containing the rs2302075 variant also revealed modest associations with hypospadias, which did not survive multiple testing corrections. None of the other tested EVC polymorphisms displayed significant association with the risk of hypospadias, either in dominant or recessive inheritance models. Conclusions The results of this study suggest that polymorphic variants of the EVC gene do not substantially contribute to the risk of hypospadias based on our study population. However, further studies should help to clarify the relationship between polymorphisms of EVC and hypospadias. PMID:26251756

  15. 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

  16. 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

  17. 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

  18. Associations of three lipoprotein lipase gene polymorphisms, lipid profiles and coronary artery disease

    PubMed Central

    DAOUD, MOHAMED S.; ATAYA, FARID S.; FOUAD, DALIA; ALHAZZANI, AMAL; SHEHATA, AFAF I.; AL-JAFARI, ABDULAZIZ A.

    2013-01-01

    Lipoprotein lipase (LPL) plays a central role in lipoprotein metabolism by hydrolyzing the core triglycerides (TGs) of circulating chylomicrons and very-low-density lipoprotein (VLDL). The effects of LPL polymorphisms on lipid levels and coronary artery disease (CAD) have been inconsistent among studies and populations. To assess the lipid profiles and distributions of three LPL gene polymorphisms in Saudi patients with CAD, the HindIII, PvuII and Ser447Ter polymorphisms in the LPL gene were analyzed in 226 patients with CAD and 110 controls. Polymerase chain reaction-restriction fragment length polymorphism was used to detect LPL gene polymorphisms. The plasma lipid profiles of the patients were determined using standard enzymatic methods. Patients in the CAD group had significantly higher triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels than controls irrespective of the HindIII, PvuII or Ser447Ter genotype. Compared to the findings in controls, the HindIII TT, PvuII TC and Ser447Ter CC genotypes were associated with significantly reduced high-density lipoprotein cholesterol (HDL-C) levels in patients with CAD (P<0.0001). In summary, there are associations between LPL gene variants and high plasma TG, TC and LDL-C levels as well as low HDL-C levels. PMID:24648989

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

    PubMed

    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.

  20. 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.

  1. 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

  2. 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

  3. SSA 04-3 LEPTIN/ADIPONECTIN IN CARDIOMETABOLIC DISEASE.

    PubMed

    Lopez-Jaramillo, Patricio

    2016-09-01

    lower in Chinese and South Asians than in Aboriginals and Europeans, and adiponectin was inversely associated with insulin resistance. The authors concluded that ethnic-specific differences in adiponectin may account for the differences in insulin resistance. It was observed that plasma adiponectin concentrations were lower for both Greenlandic Inuit boys and girls, who have a more adverse metabolic profile, than for Danish children. The differences remained after adjustment for body fat percentage, aerobic fitness, age, and puberty. However, in a large study conducted in the United States there were no significant racial or ethnic differences in circulating concentrations of adiponectin, even when adjusted for age, sex, and body composition. This result contrasts with a previous study in adults that reported that circulating concentrations of adiponectin were lower in South Asians even after adjusting for age, sex, and BMI. To explain these contrasting results, it is interesting to consider the proposal that fetal undernutrition produces poor development of structural units such as nephrons, cardiomyocytes, and beta pancreatic cells. These adaptations during fetal programming produce a negative effect in adulthood if food is more abundant in the postnatal period. Nutritional deficiencies during fetal programming through epigenetic mechanisms could affect the expression of genes that result in decreased synthesis of adiponectin. Although it is difficult to establish consistent regional differences, there appear to be considerable differences between developed and developing countries. In Latin America, a Brazilian study reported adiponectin values of 7.11 mg/mL, and we reported concentrations of 5.93 mg/mL in Colombia. In Australian women with metabolic syndrome, however, the values were 13.7 mg/mL, whereas in Indonesian women with metabolic syndrome, the values were much lower (4.9 mg/mL). In US decreased adiponectin concentrations were found in Latino compared

  4. 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

  5. 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.

  6. The APOB gene polymorphism in the pathogenesis of gallstone disease in pre- and postmenopausal women

    PubMed Central

    Rudzińska, Karolina; Kotrych, Daniel; Wolski, Hubert; Majchrzycki, Marian; Seremak-Mrozikiewicz, Agnieszka; Kosiński, Bogusław; Czerny, Bogusław

    2015-01-01

    Aim of the study The decrease in estrogen levels in the postmenopausal period changes the lipid profile by the expression of hepatic genes related to metabolism of cholesterol and bile acid synthesis that could be important in the pathogenesis of cholelithiasis. The aim of the study was to determine the APOB gene 7673C>T and 12669G>A polymorphisms in the pathogenesis of gallstones and analysis of the composition of gallstones in pre- and postmenopausal women. Material and methods The study group consisted of 94 women qualified to the laparoscopic cholecystectomy while the control group consisted of 81 women in whom gallstones and other changes in the bile ducts were excluded. Gallstones composition analysis was performed using commercially available assays. The prevalence of the APOB gene polymorphisms was determined using the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Results When assessing the composition of gallstones in pre- and postmenopausal women, we observed differences in the studied parameters. Analysis of genetic variants of APOB gene 7673C>T and 12669G>A polymorphisms showed no significant statistical differences between studied groups and controls. Conclusions Analysis of 7673C>T and 12669G>A polymorphisms showed no relationship between specific genetic variants and the risk of gallstones in pre- and postmenopausal women, pointing to the fact that the investigated polymorphisms are not relevant as prognostic factors in gallstone disease in the Caucasian population. Because of the possible contribution of a variety of factors in gallstones pathogenesis the studies are required to take account of additional environmental factors, what may indicate different occurrence between investigated polymorphisms, gallstone disease development and gallstones composition in Caucasians. PMID:26327886

  7. Distribution of paraoxonase PON1 gene polymorphisms in Mexican populations. Its role in the lipid profile.

    PubMed

    Gamboa, Ricardo; Zamora, José; Rodríguez-Pérez, José Manuel; Fragoso, José Manuel; Cardoso, Guillermo; Posadas-Romero, Carlos; Vargas-Alarcón, Gilberto

    2006-02-01

    Paraoxonase gene polymorphisms (PON1-55 and PON1-192) were determined in four Mexican populations (Mestizos, Nahuas, Teenek and Mayos) belonging to different ethnic groups. The role of these polymorphisms in the lipid profile in the Mestizo group was also analyzed. PON1 polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism. Comparison among Mexican populations showed increased frequencies of PON1-55 L allele and LL genotype and decreased frequencies of M allele and LM genotype in the three Amerindian populations when compared to Mestizos (P < 0.05). Mexicans together with Asian populations (from Japan and China) presented the highest frequencies of PON1-55 L allele (P < 0.05 when compared to Caucasian populations). Heterogeneous data were noted when PON1-192 polymorphism comparison was made. In summary, distribution frequencies of PON1 showed that Mexican populations are more related to Asians than Caucasians. This confirms previous studies with other genetic markers indicating that Native Americans have stronger genetic affinities to the Paleolithic people of North-East Asia than to other major world populations. In Mexican Mestizos, lack of correlation between PON1 polymorphisms and lipid profile was found, corroborating previous data in other populations. The present data could be helpful to understand the distribution of these polymorphisms and its role as genetic and evolutive markers in the Amerindian populations.

  8. 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.

  9. Polymorphism of the Flap Endonuclease 1 Gene in Keratoconus and Fuchs Endothelial Corneal Dystrophy

    PubMed Central

    Wojcik, Katarzyna A.; Synowiec, Ewelina; Polakowski, Piotr; Głowacki, Sylwester; Izdebska, Justyna; Lloyd, Sophie; Galea, Dieter; Blasiak, Janusz; Szaflik, Jerzy; Szaflik, Jacek P.

    2014-01-01

    Oxidative stress is implicated in the pathogenesis of many diseases, including serious ocular diseases, keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD). Flap endonuclease 1 (FEN1) plays an important role in the repair of oxidative DNA damage in the base excision repair pathway. We determined the association between two single nucleotide polymorphisms (SNPs), c.–441G>A (rs174538) and g.61564299G>T (rs4246215), in the FEN1 gene and the occurrence of KC and FECD. This study involved 279 patients with KC, 225 patients with FECD and 322 control individuals. Polymerase chain reaction (PCR) and length polymorphism restriction fragment analysis (RFLP) were applied. The T/T genotype of the g.61564299G>T polymorphism was associated with an increased occurrence of KC and FECD. There was no association between the c.–441G>A polymorphism and either disease. However, the GG haplotype of both polymorphisms was observed more frequently and the GT haplotype less frequently in the KC group than the control. The AG haplotype was associated with increased FECD occurrence. Our findings suggest that the g.61564299G>T and c.–441G>A polymorphisms in the FEN1 gene may modulate the risk of keratoconus and Fuchs endothelial corneal dystrophy. PMID:25153632

  10. 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

  11. GH gene polymorphisms and expression associated with egg laying in muscovy ducks (Cairina moschata).

    PubMed

    Wu, X; Yan, M J; Lian, S Y; Liu, X T; Li, A

    2014-02-01

    Accumulated evidence suggests that the growth hormone (GH) gene plays a physiological role in the control of reproductive function. Here, we examined the correlation between egg-laying traits and GH gene polymorphisms and expression patterns in the muscovy duck (Cairina moschata). PCR single-strand conformation polymorphism was used to identify polymorphisms in intron 3 of GH. One single nucleotide polymorphism (g.3270 A > G) was detected by sequencing, and the frequencies of the A and G alleles in the population were 0.65 and 0.35, respectively. A comparison test showed that the AA genotype group had more consecutive laying days and more eggs at 300 days than the GG genotype group (P < 0.05); however, there was no significant difference for the age at first laying (P > 0.05). Such a significant correlation between GH polymorphisms and egg-laying performance suggested that GH could be a candidate locus affecting the laying trait in muscovy duck. Furthermore, real-time fluorescent quantitative PCR demonstrated that GH is expressed in all selected tissues, but is highly expressed in the hypothalamic-pituitary-gonadal axis and heart. This unique expression pattern suggested that GH may exert its local physiological function through the autocrine or paracrine pathway during gonad development and growth in the muscovy duck. The data presented in this paper revealed GH polymorphisms and expression patterns in the muscovy duck and indicated a potential regulatory effect of GH on reproduction.

  12. Analysis of MTHFR and MTRR Gene Polymorphisms in Iranian Ventricular Septal Defect Subjects

    PubMed Central

    Pishva, Seyyed Reza; Vasudevan, Ramachandran; Etemad, Ali; Heidari, Farzad; Komara, Makanko; Ismail, Patimah; Othman, Fauziah; Karimi, Abdollah; Sabri, Mohammad Reza

    2013-01-01

    Ventricular septal defect (VSD) is one of the most common types of congenital heart defects (CHD). There are vivid multifactorial causes for VSD in which both genetic and environmental risk factors are consequential in the development of CHD. Methionine synthase reductase (MTRR) and methylenetetrahydrofolate reductase (MTHFR) are two of the key regulatory enzymes involved in the metabolic pathway of homocysteine. Genes involved in homocysteine/folate metabolism may play an important role in CHDs. In this study; we determined the association of A66G and C524T polymorphisms of the MTRR gene and C677T polymorphism of the MTHFR gene in Iranian VSD subjects. A total of 123 children with VSDs and 125 healthy children were included in this study. Genomic DNA was extracted from the buccal cells of all the subjects. The restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP) method was carried out to amplify the A66G and C524T polymorphism of MTRR and C677T polymorphism of MTHFR genes digested with Hinf1, Xho1 and Nde1 enzymes, respectively. The genotype frequencies of CC, CT and TT of MTRR gene among the studied cases were 43.1%, 40.7% and 16.3%, respectively, compared to 52.8%, 43.2% and 4.0%, respectively among the controls. For the MTRR A66G gene polymorphism, the genotypes frequencies of AA, AG and GG among the cases were 33.3%, 43.9% and 22.8%, respectively, while the frequencies were 49.6%, 42.4% and 8.0%, respectively, among control subjects. The frequencies for CC and CT genotypes of the MTHFR gene were 51.2% and 48.8%, respectively, in VSD patients compared to 56.8% and 43.2% respectively, in control subjects. Apart from MTHFR C677T polymorphism, significant differences were noticed (p < 0.05) in C524T and A66G polymorphisms of the MTRR gene between cases and control subjects. PMID:23358257

  13. Analysis of MTHFR and MTRR Gene Polymorphisms in Iranian Ventricular Septal Defect Subjects.

    PubMed

    Pishva, Seyyed Reza; Vasudevan, Ramachandran; Etemad, Ali; Heidari, Farzad; Komara, Makanko; Ismail, Patimah; Othman, Fauziah; Karimi, Abdollah; Sabri, Mohammad Reza

    2013-01-01

    Ventricular septal defect (VSD) is one of the most common types of congenital heart defects (CHD). There are vivid multifactorial causes for VSD in which both genetic and environmental risk factors are consequential in the development of CHD. Methionine synthase reductase (MTRR) and methylenetetrahydrofolate reductase (MTHFR) are two of the key regulatory enzymes involved in the metabolic pathway of homocysteine. Genes involved in homocysteine/folate metabolism may play an important role in CHDs. In this study; we determined the association of A66G and C524T polymorphisms of the MTRR gene and C677T polymorphism of the MTHFR gene in Iranian VSD subjects. A total of 123 children with VSDs and 125 healthy children were included in this study. Genomic DNA was extracted from the buccal cells of all the subjects. The restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP) method was carried out to amplify the A66G and C524T polymorphism of MTRR and C677T polymorphism of MTHFR genes digested with Hinf1, Xho1 and Nde1 enzymes, respectively. The genotype frequencies of CC, CT and TT of MTRR gene among the studied cases were 43.1%, 40.7% and 16.3%, respectively, compared to 52.8%, 43.2% and 4.0%, respectively among the controls. For the MTRR A66G gene polymorphism, the genotypes frequencies of AA, AG and GG among the cases were 33.3%, 43.9% and 22.8%, respectively, while the frequencies were 49.6%, 42.4% and 8.0%, respectively, among control subjects. The frequencies for CC and CT genotypes of the MTHFR gene were 51.2% and 48.8%, respectively, in VSD patients compared to 56.8% and 43.2% respectively, in control subjects. Apart from MTHFR C677T polymorphism, significant differences were noticed (p < 0.05) in C524T and A66G polymorphisms of the MTRR gene between cases and control subjects. PMID:23358257

  14. [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

  15. 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

  16. 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

  17. Polymorphism in two genes for B2 high sulfur proteins of wool.

    PubMed

    Rogers, G R; Hickford, J G; Bickerstaffe, R

    1994-12-01

    Variation in the nucleotide sequence of the B2 high-sulfur protein genes has not been reported previously. This paper reports 15 nucleotide substitutions in each of the genes for the B2A and B2C proteins and a length of polymorphism in the B2A gene which translates to the insertion/deletion of one 30-nucleotide repeat sequence. Evidence is presented for gene conversion occurring within the B2 high-sulfur multigene family. These DNA polymorphisms may account for some of the microheterogeneity observed in the B2 high-sulfur proteins and may also be useful genetic markers of the B2 high-sulfur protein gene loci for future use in analysing wool fibre characteristics.

  18. 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

  19. Sclera-related gene polymorphisms in high myopia

    PubMed Central

    Lin, Hui-Ju; Tsai, Yuhsin; Liu, Su-Ching; Chen, Wen-Chi; Tsai, Shih-Wei; Tsai, Fuu-Jen

    2009-01-01

    Purpose Transforming growth factor-β2 (TGF-β2), basic fibroblast growth factor (bFGF), and fibromodulin (FMOD) are important extracellular matrix components of the sclera and have been shown to be associated with the development of high myopia. Our aim was to examine the association between myopia and the polymorphisms within TGF-β2, bFGF, and FMOD. Methods The study group comprised of patients (n=195; age range: 17−24 years) with a spherical equivalent of −6.5 diopters (D) or a more negative refractive error. The control group comprised of individuals (n=94; age range: 17−25 years) with a spherical equivalent ranging from −0.5 D to +1.0 D. The subjects with astigmatism over –0.75 D were excluded from the study. High resolution melting (HRM) genotyping and restriction fragment length polymorphism (RFLP) genotyping were used to detect single nucleotide polymorphisms (SNPs). The polymorphisms detected were TGF-β2 (rs7550232 and rs991967), bFGF (rs308395 and rs41348645), and FMOD (rs7543418). Moreover, a stepwise logistic regression procedure was used to detect which of the significant SNPs contributed to the main effects of myopia development. Results There were significant differences in the frequency of the A allele and A/A genotype in TGF-β2 (rs7550232; p=0.0178 and 0.03, respectively). Moreover, the haplotype distribution of haplotype 2 (Ht2; A/A) of TGF-β2 differed significantly between the two groups (p=0.014). The results of the stepwise logistic regression procedure revealed that TGF-β2 (rs7550232) contributed significantly to the development of high myopia. Conclusions TGF-β2 is an important structure of sclera and might contribute to the formation of myopia. TGF-β2 (rs7550232) polymorphisms, A allele and A/A genotype, had a protective role against the development of high myopia. PMID:19710942

  20. Interleukin-6 gene polymorphism in Iranian patients with systemic lupus erythematosus.

    PubMed

    Godarzi, Esmaeil Moazemi; Sarvestani, Eskandar Kamali; Aflaki, Elham; Amirghofran, Zahra

    2011-02-01

    Interleukin 6 (IL-6) has been shown to be related to the pathogenesis of systemic lupus erythematosus (SLE). In the present study, the relationship between two polymorphisms in the promoter region of IL-6 gene at positions -572 G/C and -174 G/C and disease susceptibility in 401 Iranian patients with SLE was investigated using polymerase chain reaction-restriction fragment length polymorphism method. The genotype distribution and allele frequencies of IL-6 gene polymorphism at -174 position showed no significant difference between SLE patients and controls. In contrary, both allelic and genotypic frequencies at the -572 position significantly differed in SLE patients and controls. At this position, GG genotype was observed in 77.9% of patients compared to 68.9% in the control group (p < 0.014). The frequency of -572 G allele in patients (87.3%) was also higher than in controls (83.2%; p = 0.034). The haplotype study showed no significant difference between patients and healthy subjects. Study of the relationship between these polymorphisms and clinical manifestations and laboratory parameters showed an association between -174 polymorphism and the presence of antinuclear antibodies in all patients and rash and hematuria in male patients (p < 0.04). At -572 polymorphism, a significant difference with regard to photosensitivity in male patients (p = 0.04) was found. In conclusion, results of this study showed that -572 polymorphism plays an important role in susceptibility to SLE and that -174 polymorphism could influence the presence of antinuclear antibodies in the patients. PMID:20383729

  1. 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

  2. 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

  3. 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

  4. Polymorphic Regions in the Interleukin-1 Gene and Susceptibility to Chronic Periodontitis: A Genetic Association Study

    PubMed Central

    Lavu, Vamsi; Venkatesan, Vettriselvi; Lakkakula, Bhaskar Venkata Kameswara Subrahmanya; Venugopal, Priyanka; Paul, Solomon Franklin Durairaj

    2015-01-01

    Objective: The objectives of this study were to determine the association between single nucleotide polymorphisms (SNPs) in IL1B (−511, +3954), IL1A (−889, +4845), and the variable number of tandem repeats (VNTRs) polymorphism in the IL-1RN gene with chronic periodontitis susceptibility and to analyze gene–gene interactions in a hospital-based sample population from South India. Subjects and Methods: A total of 400 individuals were recruited for this study; 200 individuals with healthy gingiva and 200 chronic periodontitis patients. Genomic DNA was isolated from peripheral blood samples and genotyping was performed for the above-mentioned single nucleotide and VNTR polymorphisms by polymerase chain reaction, DNA sequencing, and agarose gel electrophoresis. Results: A higher proportion of the variant alleles were observed in the chronic periodontitis group for all the SNPs examined. The SNP at +3954 (C>T) in the IL1B gene was found to be significantly associated with chronic periodontitis (p=0.007). VNTR genotypes (χ2 value: 5.163, df=1, p=0.023) and alleles (χ2 value: 6.818, df=1, p=0.009) were found to have a significant association with chronic periodontitis susceptibility. Conclusion: In the study population examined, the SNP in the IL1B gene (+3954) and VNTR polymorphisms in the IL1RN gene were found to have a significant association with chronic periodontitis susceptibility. PMID:25710474

  5. Association of interleukin-6 gene promoter polymorphism with coronary artery disease in Pakistani families.

    PubMed

    Satti, Humayoon Shafiq; Hussain, Sabir; Javed, Qamar

    2013-01-01

    Interleukin-6 (IL-6) is a well-known inflammatory cytokine and suggested to be involved in the development of coronary artery disease (CAD). IL-6 gene expression has been investigated with controversy in CAD patients. This study investigates the association of the IL-6 gene expression with CAD, the molecular basis for the regulation of interleukin-6 expression in a Pakistani population. Our data show that the serum IL-6 levels were increased in patients with CAD compared with healthy controls and that the IL-6 gene polymorphism at -174 was more prevalent in CAD cases. There was a statistically significant association between the IL-6 gene polymorphism and CAD, which may be associated with an increased risk for the disease. Moreover, circulating IL-6 and hs-CRP levels were significantly higher in patients with CC genotype (P < 0.0001 and P < 0.0001, resp.). In a binary logistic-regression model, an independent association was found between CAD and increased serum IL-6 and hs-CRP levels and -174G>C polymorphism. This is the first report on the IL-6 expression and the IL-6 gene polymorphism in patients with CAD from Pakistan, and hence it highlights a novel risk factor for the disease.

  6. Association between polymorphisms of the insulin-degrading enzyme gene and late-onset Alzheimer disease.

    PubMed

    Wang, Shitao; He, Feiyan; Wang, Ying

    2015-06-01

    The insulin-degrading enzyme (IDE) gene is a strong positional and biological candidate for late-onset Alzheimer disease (LOAD) susceptibility, with recent studies independently demonstrating an association between IDE gene variants and LOAD. However, previous data have been controversial. To investigate the relationship between IDE gene polymorphisms and LOAD risk, a case-control association study of 406 Han Chinese participants in Xinjiang, China, was undertaken. The LOAD and control groups consisted of 202 and 204 participants, respectively. The single-nucleotide polymorphisms rs1887922 and rs1999764 of the IDE gene were linked to LOAD incidence. The presence of the CT+CC genotype of rs1999764 had a protective effect compared to the TT genotype (adjusted P=.0001; odds ratio [OR]=0.226; 95% confidence interval [CI]=0.116-0.441), while the CT+CC genotype of rs1887922 was associated with increased LOAD risk (adjusted P=.0001; OR=3.640; 95% CI=1.889-7.016). Moreover, the effects of rs1887922 and rs1999764 were associated with LOAD risk independent of the apolipoprotein E ∊4 polymorphism and were more significant in men and women, respectively. These results demonstrate that the polymorphisms rs1887922 and rs1999764 of the IDE gene are associated with LOAD susceptibility in the Xinjiang Han population.

  7. 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

  8. Adiponectin, leptin, and yoga practice.

    PubMed

    Kiecolt-Glaser, Janice K; Christian, Lisa M; Andridge, Rebecca; Hwang, Beom Seuk; Malarkey, William B; Belury, Martha A; Emery, Charles F; Glaser, Ronald

    2012-12-01

    To address the mechanisms underlying hatha yoga's potential stress-reduction benefits, we compared adiponectin and leptin data from well-matched novice and expert yoga practitioners. These adipocytokines have counter-regulatory functions in inflammation; leptin plays a proinflammatory role, while adiponectin has anti-inflammatory properties. Fifty healthy women (mean age=41.32, range=30-65), 25 novices and 25 experts, provided fasting blood samples during three separate visits. Leptin was 36% higher among novices compared to experts, P=.008. Analysis of adiponectin revealed a borderline effect of yoga expertise, P=.08; experts' average adiponectin levels were 28% higher than novices across the three visits. In contrast, experts' average adiponectin to leptin ratio was nearly twice that of novices, P=.009. Frequency of self-reported yoga practice showed significant negative relationships with leptin; more weeks of yoga practice over the last year, more lifetime yoga sessions, and more years of yoga practice were all significantly associated with lower leptin, with similar findings for the adiponectin to leptin ratio. Novices and experts did not show even marginal differences on behavioral and physiological dimensions that might represent potential confounds, including BMI, central adiposity, cardiorespiratory fitness, and diet. Prospective studies addressing increased risk for type II diabetes, hypertension, and cardiovascular disease have highlighted the importance of these adipocytokines in modulating inflammation. Although these health risks are clearly related to more extreme values then we found in our healthy sample, our data raise the possibility that longer-term and/or more intensive yoga practice could have beneficial health consequences by altering leptin and adiponectin production. PMID:22306535

  9. Association Between Polymorphisms of DRD2, COMT, DBH, and MAO-A Genes and Migraine Susceptibility

    PubMed Central

    Chen, Hu; Ji, Chun-Xue; Zhao, Lian-Li; Kong, Xiang-Jun; Zeng, Xian-Tao

    2015-01-01

    Abstract Some epidemiological studies have investigated the relationship between genetic polymorphisms of DRD2, COMT, DBH, and MAO-A and migraine susceptibility, but the results are still inconsistent. Thus, our aim was to further assess the association through a meta-analysis. We examined 5 single nucleotide polymorphisms (SNPs) in 4 genes, including DRD2 rs1799732 and rs6275, DBH rs7239728, MAI-A-VNTR, and COMT rs4680, and performed a meta-analysis of 11 published case–control studies including 3138 cases and 4126 controls. Odd ratios (ORs) with 95% confidence intervals (95% CIs) were used to evaluate the association between the 5 genetic polymorphisms and migraine susceptibility. There was no significant relationship between migraine susceptibility and 4 genetic polymorphisms of DRD2 rs1799732 and rs6275, DBH rs7239728, and MAO-A-VNTR. Nevertheless, decreased risk of migraine was observed to be in association with COMT rs4680 polymorphism in overall analysis (AA vs. GG + GA: OR = 0.76, 95% CI = 0.60–0.97, PHet > 0.642, I2 = 0), and in Caucasian group after subgroup analysis (AA vs. GG + GA: OR = 0.75, 95% CI = 0.58–0.96, PHet > 0.433, I2 = 0). Studied polymorphisms of DRD2, DBH, and MAO-A genes may not be associated with migraine susceptibility. However, COMT rs4680 polymorphism may decrease the risk of migraine, especially in Caucasians. The failure to evaluate environmental influence and provide adjusted effect size estimates highlights the need for additional studies in a large number to take these factors into consideration, thus better elucidating the role of the genes tested in migraine. PMID:26632697

  10. Cytokine gene polymorphisms and atopic disease in two European cohorts. (ECRHS-Basel and SAPALDIA)

    PubMed Central

    Imboden, M; Nieters, A; Bircher, AJ; Brutsche, M; Becker, N; Wjst, M; Ackermann-Liebrich, U; Berger, W; Probst-Hensch, NM

    2006-01-01

    Background Atopy and allergic phenotypes are biologically characterized by an imbalanced T helper cell response skewed towards a type 2 (TH2) immune response associated with elevated serum immunoglobulin E (IgE) levels. Polymorphisms in cytokine genes might modulate regulation of the TH1/TH2 balance. We thus aimed at reproducing our previous findings from a European study population on the association of various cytokine polymorphisms with self-reported hay fever as well as increased total and specific IgE levels in two comparable study populations. Methods Two prospective Caucasian cohorts were used. In the Basel center of the European Community Respiratory Health Survey (ECRHS, n = 418) ten distinct cytokine polymorphisms of putative functional relevance were genotyped. In the Swiss cohort Study on Air Pollution And Lung Disease In Adults (SAPALDIA, n = 6003) two cytokine polymorphisms were genotyped. The associations of these polymorphisms with atopy were estimated by covariance and logistic regression analysis. Results We confirmed IL4, IL10, IL6 and IL18 as candidate genes for atopic health outcomes. In the large, well-characterized SAPALDIA cohort the IL6(-174G>C) and IL18(-137G>C) polymorphisms were associated with circulating total IgE concentrations in subjects with hay fever. The IL18(-137G>C) polymorphism was also associated with the prevalence of hay fever. Conclusion Comprehensive characterization of genetic variation in extended cytokine candidate gene regions is now needed. Large study networks must follow to investigate the association of risk patterns defined by genetic predisposing and environmental risk factors with specific atopic phenotypes. PMID:16759385

  11. 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

  12. 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

  13. CYP19 (cytochrome P450 aromatase) gene polymorphism in murrah buffalo heifers of different fertility performance.

    PubMed

    Suneel Kumar, O; Sharma, Deepti; Singh, Dheer; Sharma, M K

    2009-06-01

    The most common cause of infertility in buffaloes is anestrum. During late maturity the ovaries are in a state of true anestrum. One of the predominant causes of true anestrum is a low level of ovarian estrogens. The key enzyme in estrogen biosynthesis is cytochrome P450 aromatase, encoded by CYP19 gene. In the present study, CYP19 gene polymorphism was analyzed by Single Strand Conformational Polymorphism (SSCP) in buffaloes of different fertility performance. The SSCP and sequence analysis revealed 4 allelic variants in coding exons and introns which unaltered the protein sequence. However, a significant polymorphism (T/C heterozygote) was found near TATA binding protein region in regulatory part (a facet of promoter II) at position 23 of CYP19 exon 2, in all late matured and 50% of late maturing animals. Based on these observations and remarks of earlier workers, a hypothesis is proposed for the physiology of late maturity in buffaloes. PMID:19101001

  14. NRAMP1 and VDR Gene Polymorphisms in Susceptibility to Tuberculosis in Venezuelan Population

    PubMed Central

    Fernández-Mestre, Mercedes; Villasmil, Ángel; Takiff, Howard; Fuentes Alcalá, Zhenia

    2015-01-01

    Natural resistance-associated macrophage protein (Nramp1) and the vitamin D receptor (VDR) are central components of the innate and adaptive immunity against Mycobacterium tuberculosis, and associations between susceptibility to tuberculosis and polymorphisms in the genes NRAMP and VDR have been sought in geographically diverse populations. We investigated associations of NRAMP1 and VDR gene polymorphisms with susceptibility to TB in the Venezuelan population. The results suggest the absence of any association between VDR variants FokI, ApaI, and TaqI and susceptibility to tuberculosis. In contrast, the NRAMP1 3′UTR variants were associated with susceptibility to M. tuberculosis infection, as seen in the comparisons between TST+ and TST− controls, and also with progression to TB disease, as shown in the comparisons between TB patients and TST+ controls. This study confirms the previously described association of the NRAMP1 3′UTR polymorphism with M. tuberculosis infection and disease progression. PMID:26578819

  15. [Research advances in gene polymorphisms in biological pathways of drugs for asthma].

    PubMed

    Guo, Dan-Dan; Zheng, Xiang-Rong

    2016-06-01

    The studies on gene polymorphisms in biological pathways of the drugs for the treatment of asthma refer to the studies in which pharmacogenetic methods, such as genome-wide association studies, candidate gene studies, genome sequencing, admixture mapping analysis, and linkage disequilibrium, are used to identify, determine, and repeatedly validate the effect of one or more single nucleotide polymorphisms on the efficacy of drugs. This can provide therapeutic strategies with optimal benefits, least side effects, and lowest costs to patients with asthma, and thus realize individualized medicine. The common drugs for asthma are β2 receptor agonists, glucocorticoids, and leukotriene modifiers. This article reviews the research achievements in polymorphisms in biological pathways of the common drugs for asthma, hoping to provide guidance for pharmacogenetic studies on asthma in future and realize individualized medicine for patients with asthma soon.

  16. Genotype x nutrient association of common polymorphisms in obesity-related genes with food preferences and time structure of energy intake.

    PubMed

    Bienertová-Vasků, Julie; Bienert, Petr; Forejt, Martin; Tomandl, Josef; Brázdová, Zuzana; Vasků, Anna

    2010-02-01

    Personal food preferences can either enhance or suppress the development of obesity and the selection and proportion of macronutrients in the diet seem to have a heritable component. In the present study, we therefore focused on dietary composition as a specific trait related to obesity and we determined whether genetic variations in leptin (LEP), LEP receptor (LEPR), adiponectin (ADIPOQ), IL-6 and pro-opiomelanocortin (POMC) underlie specific native food preferences and obesity-related anthropometric parameters. The total of 409 individuals of Czech Caucasian origin were enrolled into the present study and 7 d food records were obtained from the study subjects along with selected anthropometric measurements. In a subset of study subjects, plasma levels of ADIPOQ, LEP and soluble LEPR were measured. Independently of the BMI of the individuals, common variations in LEP and LEPR genes were associated with specific eating patterns, mainly with respect to timing of eating. The LEP + 19A/G polymorphism served as an independent predictor for BMI, percentage of body fat and skinfold thickness and significantly affected the time structure of the daily energy intake. The POMC RsaI polymorphism was associated with percentage of body fat. The ADIPOQ 45 T/G polymorphism was associated with the thickness of the subscapular skinfold. The LEPR Gln223Arg polymorphism was associated with multiple parameters, including diastolic blood pressure, meal sizes during the day and plasma ADIPOQ levels. In a separate analysis, soluble leptin receptor (sObR) plasma levels and LEP:sObR ratio were significantly correlated with systolic blood pressure (beta = - 0.66, P = 0.002; beta = - 1.23, P = 0.02) and sObR plasma levels also served as an independent predictor for diastolic blood pressure (beta = - 0.50; P = 0.04). To conclude, we report common allelic variants associated with specific feeding behaviour and obesity-related anthropometric traits. Moreover, we identified allelic variants that

  17. 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.

  18. 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

  19. Toll-like receptors gene polymorphisms may confer increased susceptibility to breast cancer development.

    PubMed

    Theodoropoulos, George E; Saridakis, Vasilios; Karantanos, Theodoros; Michalopoulos, Nikolaos V; Zagouri, Flora; Kontogianni, Panagiota; Lymperi, Maria; Gazouli, Maria; Zografos, George C

    2012-08-01

    Toll-like receptor (TLR) activation may be an important event in tumor cell immune evasion. TLR2 and TLR4 gene polymorphisms have been related to increased susceptibility to cancer development in various organs. 261 patients and 480 health individuals were investigated for genotype and allelic frequencies of a 22-bp nucleotide deletion (-196 to -174del) in the promoter of TLR2 gene as well as two polymorphisms causing amino acid substitutions (Asp299Gly and Thr399Ile) in TLR4 gene. As far as (-196 to -174del) in TLR2 gene is concerned ins/del and del/del genotypes and del allele were significantly more frequent in breast cancer patients compared to healthy controls. Considering Asp299Gly replacement of TLR4 gene, Gly carriers (Asp/Gly & Gly/Gly genotype) and Gly allele were overrepresented among the breast cancer cases. The -174 to -196del of TLR2 gene and Asp299Gly of TLR4 gene polymorphisms may confer an increased susceptibility to breast cancer development.

  20. Early failure of dental implants and TNF-alpha (G-308A) gene polymorphism.

    PubMed

    Campos, Maria Isabela Guimarães; dos Santos, Maria Cristina Leme Godoy; Trevilatto, Paula Cristina; Scarel-Caminaga, Raquel Mantuaneli; Bezerra, Fábio José Barbosa; Line, Sergio Roberto Peres

    2004-03-01

    Tumor necrosis factor-alpha (TNF-alpha) is a potent inflammatory mediator with bone resorption activity. Polymorphisms in the promoter region of the human TNF-alpha gene have been shown to affect the levels of this cytokine and have been associated with a variety of diseases. The aim of this study was to investigate the possible relationship between early implant failure and a single nucleotide polymorphism (SNP) in the -308 promoter region of the TNF-alpha gene. A sample of 66 nonsmokers was divided into 2 groups: a test group comprising 28 patients (mean age, 52.7 years) with one or more early failed implants and a control group consisting of 38 individuals (mean age, 43.2 years) with one or more healthy implants. Genomic DNA from buccal mucosa was amplified by the polymerase chain reaction (PCR), analyzed by restriction fragment length polymorphism (RFLP), and submitted to polyacrylamide gel electrophoresis to distinguish allele G and allele A of the TNF-alpha (-308) gene polymorphism. Differences in the allele and genotype frequencies between control and test groups were assessed by chi-squared test (P <0.05). No significant difference was observed in the allele (P = 0.4635) and genotype (P = 0.4445) distribution of the polymorphism when control and failure groups were compared. The results indicate that the TNF-alpha (G-308A) gene polymorphism is not associated with early implant failure, suggesting that its presence alone does not constitute a genetic risk factor for implant loss in the Brazilian population. PMID:15017311

  1. 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.

  2. Vitamin D receptor gene FokI polymorphisms and tuberculosis susceptibility: a meta-analysis

    PubMed Central

    Cao, Yan; Cao, Zhihong; Cheng, Xiaoxing

    2016-01-01

    Introduction The association between FokI polymorphism of vitamin D receptor (VDR) and tuberculosis (TB) susceptibility has been investigated previously; however, the results were inconsistent and conflicting. In the present study, a meta-analysis was performed to assess the relationship between VDR FokI gene polymorphism and the risk of TB. Material and methods Databases including PubMed and Embase were searched for genetic association studies of FokI polymorphism of vitamin D receptor (VDR) and TB. Data were extracted by two independent authors and the pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to assess the strength of the association between VDR FokI gene polymorphism and TB risk. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. Results Thirty-four studies with a total of 5669 cases and 6525 controls were reviewed in the present meta-analysis. A statistically significant correlation was found between VDR FokI gene polymorphism and increased TB risk in two comparison models: the homozygote model (ff vs. FF: OR = 1.37, 95% CI: 1.17–1.60; Pheterogeneity = 0.001) and the recessive model (ff vs. Ff + FF: OR = 1.32, 95% CI: 1.14–1.52; Pheterogeneity = 0.006). Meta-regression found no source contributing to heterogeneity. However, sub-group analyses revealed that there was a statistically increased TB risk in the East and Southeast Asian population. Conclusions Synthesis of the available studies suggests that homozygosity for the FokI polymorphism of the VDR gene might be associated with an increased TB risk, especially in the East and Southeast Asian population. Additional well-designed, larger-scale epidemiological studies among different ethnicities are needed. PMID:27695504

  3. 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.

  4. Vitamin D receptor gene FokI polymorphisms and tuberculosis susceptibility: a meta-analysis

    PubMed Central

    Cao, Yan; Cao, Zhihong; Cheng, Xiaoxing

    2016-01-01

    Introduction The association between FokI polymorphism of vitamin D receptor (VDR) and tuberculosis (TB) susceptibility has been investigated previously; however, the results were inconsistent and conflicting. In the present study, a meta-analysis was performed to assess the relationship between VDR FokI gene polymorphism and the risk of TB. Material and methods Databases including PubMed and Embase were searched for genetic association studies of FokI polymorphism of vitamin D receptor (VDR) and TB. Data were extracted by two independent authors and the pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to assess the strength of the association between VDR FokI gene polymorphism and TB risk. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. Results Thirty-four studies with a total of 5669 cases and 6525 controls were reviewed in the present meta-analysis. A statistically significant correlation was found between VDR FokI gene polymorphism and increased TB risk in two comparison models: the homozygote model (ff vs. FF: OR = 1.37, 95% CI: 1.17–1.60; Pheterogeneity = 0.001) and the recessive model (ff vs. Ff + FF: OR = 1.32, 95% CI: 1.14–1.52; Pheterogeneity = 0.006). Meta-regression found no source contributing to heterogeneity. However, sub-group analyses revealed that there was a statistically increased TB risk in the East and Southeast Asian population. Conclusions Synthesis of the available studies suggests that homozygosity for the FokI polymorphism of the VDR gene might be associated with an increased TB risk, especially in the East and Southeast Asian population. Additional well-designed, larger-scale epidemiological studies among different ethnicities are needed.

  5. A Microsatellite Polymorphism in IGF1 Gene Promoter and Timing of Natural Menopause in Caucasian Women

    PubMed Central

    Kaczmarek, Maria; Pacholska-Bogalska, Joanna; Kwaśniewski, Wojciech; Kotarski, Jan; Halerz-Nowakowska, Barbara; Goździka-Józefiak, Anna

    2015-01-01

    Background: Genes involved in the IGF-1 aging pathways in the human ovary can be considered strong candidates for predictors of the natural menopause timing. This study evaluates the association between a cytosine-adenine (CA) microsatellite polymorphism in the IGF1 gene promoter P1 and age at natural menopause. Methods: Genomic DNA was extracted from the peripheral blood, PCR was performed using primers designed to amplify the polymorphic (CA)n repeat of the human IGF1 gene, an allele dose effect for the most common (CA)19 repeats allele, Cox proportional hazard regression models and the Kaplan-Meier cumulative survivorship method with the log-rank test were used to determine statistical significance of studied associations in a sample of 257 Polish women aged 40-58 years. Results: Crude Cox proportional hazard regression analysis confirmed the association between the IGF1 gene polymorphism and the menopause timing (p=0.038). This relationship remained statistically significant after controlling for other menopause confounders in multivariate modelling. Out of the input variables, the (CA)n polymorphism in the IGF1 gene promoter, age at menarche and smoking status were independent covariates of the natural menopause timing (χ2 =12.845; df=3; p=0.034). The onset of menopause at a younger age was likely associated with the IGF1 genotype variant not carrying the (CA)19 repeats allele, menarche before the age of 12 and a current cigarette smoker status (HR=1.6). Conclusion: This study provides evidence that a common cytosine-adenine (CA) microsatellite repeat polymorphism in the P1 promoter region of the IGF1 gene is an independent predictive factor for age at natural menopause in Caucasian women also after adjusting for other menopause covariates. PMID:25552916

  6. Effects of leptin and leptin receptor gene polymorphisms on lung cancer.

    PubMed

    Unsal, Meftun; Kara, Nurten; Karakus, Nevin; Tural, Sengul; Elbistan, Mehmet

    2014-10-01

    Leptin (LEP), an adipocyte-derived cytokine, has been reported to participate in carcinogenesis. Elevated levels of systemic and pulmonary LEP are associated with diseases related to lung injury and lung cancer. The purpose of the present study was to investigate if the LEP and leptin receptor (LEPR) gene polymorphisms are associated with lung cancer in a cohort of Turkish population. One hundred and sixty-two lung cancer patients and 130 healthy controls were included in the study. The genotypes of LEP gene -2548G > A and LEPR gene Q223R polymorphisms were determined using polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP) analysis. The genotype frequencies of LEP -2548G > A polymorphism showed statistically significant differences between lung cancer patients and controls (p = 0.007). GA + AA genotypes and A allele of LEP -2548G > A polymorphism was found to be susceptibility factors for lung cancer (p = 0.003, odds ratio (OR) 2.32, 95 % confidence interval (CI) 1.32-4.10; p = 0.003, OR 1.65, 95 % CI 1.18-2.29, respectively). The genotype and allele frequencies of LEPR Q223R polymorphism did not show any statistically significant differences between lung cancer patients and controls (p = 0.782 and p = 0.762, respectively). Although AA-QQ and AA-QR combined genotypes of LEP -2548G > A-LEPR Q223R loci were significantly higher in lung cancer patients (p = 0.020 and p = 0.047, respectively), GG-QQ, GG-QR, and AA-RR combined genotypes were significantly higher in control group. As a result, susceptibility effects of LEP -2548G > A polymorphism alone or in combination with LEPR Q223R polymorphism on lung cancer were observed. Further studies are necessary to prove the association of LEP and LEPR gene polymorphisms with lung cancer.

  7. 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...

  8. Relationship between angiotensin I-converting enzyme insertion/deletion gene polymorphism and retinal vein occlusion

    PubMed Central

    2014-01-01

    To evaluate the association between angiotensin I-converting enzyme insertion/deletion (ACE I/D) gene polymorphism and retinal vein occlusion (RVO). A total of 80 patients with retinal vein occlusion who was admitted to the Eye Department of Kartal Training and Research Hospital between 2008 and 2011, and 80 subjects were enrolled in this retrospective case–control study. Patients who experienced RVO within one week to six months of study enrolment were included, and those with coronary artery diseases, prior myocardial infarction history and coagulation disturbances were excluded from the study. The diagnosis was made by ophthalmoscopic fundus examination and fluorescein angiography. The ACE gene I/D polymorphism was determined by polymerase chain reaction, and the ACE gene was classified into three types: I/I, I/D and D/D. In multivariate logistic regression analysis, ACE D/D genotype (p = 0.035), diabetes-mellitus (p = 0.019) and hypertension (p = 0.001) were found to be independent predictive factors for RVO. The results of the present study reveal that ACE D/D polymorphism is an independent predictive factor for RVO. However, one cannot definitely conclude that ACE gene polymorphism is a risk factor for retinal vein occlusion. PMID:25161389

  9. 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.…

  10. 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...

  11. 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

  12. 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...

  13. High-density polymorphisms analysis of 23 candidate genes for association with bone mineral density.

    PubMed

    Giroux, Sylvie; Elfassihi, Latifa; Clément, Valérie; Bussières, Johanne; Bureau, Alexandre; Cole, David E C; Rousseau, François

    2010-11-01

    Osteoporosis is a bone disease characterized by low bone mineral density (BMD), a highly heritable and polygenic trait. Women are more prone than men to develop osteoporosis due to a lower peak bone mass and accelerated bone loss at menopause. Peak bone mass has been convincingly shown to be due to genetic factors with heritability up to 80%. Menopausal bone loss has been shown to have around 38% to 49% heritability depending on the site studied. To have more statistical power to detect small genetic effects we focused on premenopausal women. We studied 23 candidate genes, some involved in calcium and vitamin-D regulation and others because estrogens strongly induced their gene expression in mice where it was correlated with humerus trabecular bone density. High-density polymorphisms were selected to cover the entire gene variability and 231 polymorphisms were genotyped in a first sample of 709 premenopausal women. Positive associations were retested in a second, independent, sample of 673 premenopausal women. Ten polymorphisms remained associated with BMD in the combined samples and one was further associated in a large sample of postmenopausal women (1401 women). This associated polymorphism was located in the gene CSF3R (granulocyte colony stimulating factor receptor) that had never been associated with BMD before. The results reported in this study suggest a role for CSF3R in the determination of bone density in women.

  14. 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…

  15. A Scan for Human-Specific Relaxation of Negative Selection Reveals Unexpected Polymorphism in Proteasome Genes

    PubMed Central

    Somel, Mehmet; Wilson Sayres, Melissa A.; Jordan, Gregory; Huerta-Sanchez, Emilia; Fumagalli, Matteo; Ferrer-Admetlla, Anna; Nielsen, Rasmus

    2013-01-01

    Environmental or genomic changes during evolution can relax negative selection pressure on specific loci, permitting high frequency polymorphisms at previously conserved sites. Here, we jointly analyze population genomic and comparative genomic data to search for functional processes showing relaxed negative selection specifically in the human lineage, whereas remaining evolutionarily conserved in other mammals. Consistent with previous studies, we find that olfactory receptor genes display such a signature of relaxation in humans. Intriguingly, proteasome genes also show a prominent signal of human-specific relaxation: multiple proteasome subunits, including four members of the catalytic core particle, contain high frequency nonsynonymous polymorphisms at sites conserved across mammals. Chimpanzee proteasome genes do not display a similar trend. Human proteasome genes also bear no evidence of recent positive or balancing selection. These results suggest human-specific relaxation of negative selection in proteasome subunits; the exact biological causes, however, remain unknown. PMID:23699470

  16. 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

  17. Presenilin-1 gene intronic polymorphism in sporadic and familial Alzheimer's disease.

    PubMed

    Sorbi, S; Nacmias, B; Tedde, A; Forleo, P; Piacentini, S; Latorraca, S; Amaducci, L

    1997-01-31

    A recent observation has shown a genetic association between an intronic polymorphism in the Presenilin-1 (PS-1) gene and late onset Alzheimer's disease (AD). The homozygosity of the 1 allele in the PS-1 gene was associated with a doubling of the risk for late onset AD. However, contrasting results have been published. We analyzed the distribution of the PS-1 intronic polymorphism in patients with sporadic AD and in seven familial AD (FAD) families carrying pathogenetic mutations in the amyloid precursor protein (APP) and Presenilin (PS-1 and PS-2) genes. Significant differences in PS-1 allele frequencies were observed in the Presenilin genes mutated families but not in late onset AD patients and in APP mutated families. PMID:9111746

  18. RUNX3 gene polymorphisms and haplotypes in Mexican patients with colorectal cancer.

    PubMed

    Suárez-Villanueva, S; Ayala-Madrigal, M L; Peregrina-Sandoval, J; Macías-Gómez, N; Ramírez-Ramírez, R; Muñiz-Mendoza, R; Moreno-Ortiz, J M; Centeno-Flores, M; Maciel-Gutiérrez, V; Cabrales, E; Gutiérrez-Angulo, M

    2015-01-01

    We analyzed a possible association between RUNX3 gene polymorphisms and haplotypes in Mexican patients with colorectal cancer (CRC). Genomic DNA samples were obtained from the peripheral blood of 176 Mexican patients with CRC at diagnosis and from 195 individuals that formed the control group. The polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism. Association was estimated by odds ratio (OR). The haplotypes and linkage disequilibrium were established using the Arlequin v3.5 software. We found that the RUNX3 polymorphisms analyzed were in Hardy-Weinberg equilibrium. The RUNX3 rs2236852 AA genotype and A allele showed association with CRC (OR = 0.39, 95%CI = 0.21-0.73, P < 0.01; OR = 0.65, 95%CI = 0.49-0.87, P < 0.01, respectively), while the rs6672420, rs11249206, and rs760805 polymorphisms did not show significant association with CRC. The TA haplotype (SNPs rs760805 and rs2236852) showed an increased risk for CRC (OR = 2.52, 95%CI = 1.47-4.30, P < 0.001). In conclusion, we found that the AA genotype and A allele of rs2236852 polymorphism confer a decreased CRC risk, while the TA haplotype appears to increase the risk of CRC development in Mexican patients. PMID:26634516

  19. Functional Gene Polymorphism to Reveal Species History: The Case of the CRTISO Gene in Cultivated Carrots

    PubMed Central

    Clotault, Jérémy; Huet, Sébastien; Briard, Mathilde; Peltier, Didier; Geoffriau, Emmanuel

    2013-01-01

    Background Carrot is a vegetable cultivated worldwide for the consumption of its root. Historical data indicate that root colour has been differentially selected over time and according to geographical areas. Root pigmentation depends on the relative proportion of different carotenoids for the white, yellow, orange and red types but only internally for the purple one. The genetic control for root carotenoid content might be partially associated with carotenoid biosynthetic genes. Carotenoid isomerase (CRTISO) has emerged as a regulatory step in the carotenoid biosynthesis pathway and could be a good candidate to show how a metabolic pathway gene reflects a species genetic history. Methodology/Principal Findings In this study, the nucleotide polymorphism and the linkage disequilibrium among the complete CRTISO sequence, and the deviation from neutral expectation were analysed by considering population subdivision revealed with 17 microsatellite markers. A sample of 39 accessions, which represented different geographical origins and root colours, was used. Cultivated carrot was divided into two genetic groups: one from Middle East and Asia (Eastern group), and another one mainly from Europe (Western group). The Western and Eastern genetic groups were suggested to be differentially affected by selection: a signature of balancing selection was detected within the first group whereas the second one showed no selection. A focus on orange-rooted carrots revealed that cultivars cultivated in Asia were mainly assigned to the Western group but showed CRTISO haplotypes common to Eastern carrots. Conclusion The carotenoid pathway CRTISO gene data proved to be complementary to neutral markers in order to bring critical insight in the cultivated carrot history. We confirmed the occurrence of two migration events since domestication. Our results showed a European background in material from Japan and Central Asia. While confirming the introduction of European carrots in Japanese

  20. Association of beta 2 adrenoceptor gene polymorphisms in Malaysian hypertensive subjects.

    PubMed

    Komara, M; Vasudevan, R; Ismail, P; Bakar, S A; Pishva, S R; Heidari, F

    2014-04-16

    The sympathetic nervous system plays a major role in blood pressure regulation. Beta 2 (β2) adrenoceptor gene polymorphisms have been associated with hypertension in different populations with conflicting results. We examined the association of three common polymorphisms, Arg16Gly, Gln27Glu, and Thr164Ile, of the β2 adrenoceptor gene in Malaysian hypertensive subjects. A total of 160 hypertensive and control subjects were recruited. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and anthropometric measurements were obtained from each subject. Biochemical analyses of lipid profiles were conducted with an autoanalyzer. DNA samples were extracted from blood and buccal cells. Genotyping was accomplished with polymerase chain reaction-restriction fragment length polymorphism. SBP, DBP, body mass index, and biochemical factors all differed significantly between case and control subjects (P < 0.05). The genotype frequencies of Arg16Arg, Arg16Gly, and Gly16Gly were 22.5, 70, and 7.5% among cases and 33.1, 63.1, and 3.8% among controls, respectively. The genotype frequencies of Gln27Gln, Gln27Glu, and Glu27Glu among cases were 41.1, 50, and 1.9% compared to 77.5, 20.6, and 1.9% among controls, respectively. In this study, the Gln27Glu polymorphism was significantly associated with Malaysian hypertensive subjects (P < 0.05). Therefore, the Gln27Glu polymorphism of the β2 adrenoceptor could be a risk factor associated with hypertension among Malaysians.

  1. Relation of polymorphism of the histidine decarboxylase gene to chronic heart failure in Han Chinese.

    PubMed

    He, Gong-Hao; Cai, Wen-Ke; Meng, Jing-Ru; Ma, Xue; Zhang, Fan; Lu, Jun; Xu, Gui-Li

    2015-06-01

    Histidine decarboxylase (HDC) is a key determinant of the levels of endogenous histamine that has long been recognized to play important pathophysiological roles during development of chronic heart failure (CHF). Meanwhile, certain genetic variants in HDC gene were reported to affect the function of HDC and associated with histamine-related diseases. However, the relation between polymorphisms of HDC gene and CHF risk remains unclear. This study aims to investigate the associations between 2 nonsynonymous HDC polymorphisms (rs17740607 and rs2073440) and CHF. We designed a 2-stage case-control study, in which we genotyped 439 patients with CHF and 467 healthy controls recruited in Xi'an, China, and replicated this study in 413 patients with CHF and 452 healthy subjects in Kunming, China. We also performed in vitro experiments to further validate the functional consequences of variants positively associated with CHF. The rs17740607 polymorphism showed replicated associations with all-cause CHF according to genotype and allele distribution and also under a dominant and additive genetic model after adjusted for traditional cardiovascular-related factors. Functional experiments further demonstrated that rs17740607 polymorphism decreased the HDC activity. In conclusion, HDC rs17740607 polymorphism is at least a partial loss-of-function variant and acts as a protective factor against CHF, which provides novel highlights for investigating the contribution of CHF.

  2. Association of MMP-9 Gene Polymorphisms with Glaucoma: A Meta-Analysis.

    PubMed

    Zhang, Yiqun; Wang, Mingjie; Zhang, Sunyi

    2016-01-01

    The aim of this study was to evaluate the associations between matrix metalloproteinase-9 (MMP-9) gene polymorphisms (rs17576 and rs3918249) and glaucoma risk. All eligible studies were searched in PubMed, Embase, the Cochrane Library and the China Knowledge Resource Integrated Database. Pooled odds ratios and 95% confidence intervals were used to assess associations between MMP-9 gene polymorphisms and glaucoma. Seven studies on rs17576 (1,357 cases and 1,432 controls) and 3 studies on rs3918249 (550 cases and 794 controls) were included. The results suggest that rs17576 was not associated with glaucoma risk based on current publications. However, stratification analyses indicated that GG genotypes increased the risk of primary open-angle glaucoma in a recessive model (GG vs. AA + AG). The rs3918249 polymorphism was also associated with a decreased risk of glaucoma, especially for Caucasian patients. To sum up, our data indicate that rs17576 polymorphism is not related to glaucoma and rs3918249 polymorphism might be a protective factor against glaucoma.

  3. Relationship between estrogen receptor 1 gene polymorphisms and postmenopausal osteoporosis of the spine in Chinese women.

    PubMed

    Shang, D P; Lian, H Y; Fu, D P; Wu, J; Hou, S S; Lu, J M

    2016-01-01

    The purpose of this study was to evaluate single nucleotide polymorphism (SNP) variants of the estrogen receptor 1 gene (ESR1) at rs2234693 and rs9340799, as well as to investigate the relationship between ESR gene polymorphisms and postmenopausal osteoporosis (OP) of the spine in Chinese women. We recruited 198 postmenopausal women with OP and 276 healthy women between May 2012 and September 2015 in Zhongshan Hospital. Dual energy x-ray absorptiometry was used to measure the bone mineral density (BMD) of the lumbar vertebrae in all subjects. In addition, PCR-restriction fragment length polymorphism based analysis was conducted to identify the genotypes of ESR1. The distribution of ESR1 in the osteoporosis group and the control group was determined; the relationship between ESR polymorphisms and BMD was analyzed. The distributions of BMD were: TT < TC < CC, GG < AG < AA. The TT, TTGG, and TCGG genotypes were found to be lower as compared to the other genotypes. Stratified analysis suggested that the TT genotype and the combined genotypes TTGG and TCGG were significantly higher in the OP group as compared to the control group (P < 0.01). Therefore, ESR1 polymorphisms at rs2234693 and rs9340799 may be associated with OP, and could be used as markers to screen those with high risks to postmenopausal OP in Chinese women. PMID:27323138

  4. XPG Gene Polymorphisms Contribute to Colorectal Cancer Susceptibility: A Two-Stage Case-Control Study

    PubMed Central

    Hua, Rui-Xi; Zhuo, Zhen-Jian; Zhu, Jinhong; Zhang, Shao-Dan; Xue, Wen-Qiong; Zhang, Jiang-Bo; Xu, Hong-Mei; Li, Xi-Zhao; Zhang, Pei-Fen; He, Jing; Jia, Wei-Hua

    2016-01-01

    Previous studies have reported that xeroderma pigmentosum group G (XPG) gene polymorphisms may modulate colorectal cancer (CRC) susceptibility. In this study, we performed a two-stage case-control study to comprehensively investigate the associations of five polymorphisms in the XPG gene with CRC risk in 1,901 cases and 1,976 controls from Southern China, including rs2094258 C>T, rs751402 C>T, rs2296147 T>C, rs1047768 T>C and rs873601 G>A. After combining data from two stages, we found that three of the studied polymorphisms (rs2094258 C>T, rs751402 C>T, and rs873601 G>A) were significantly associated with CRC susceptibility. After adjustment for age and gender, multivariate logistic regression analysis indicated that carriers of the rs2094258 T alleles had an increased CRC risk [CT vs. CC: adjusted odds ratio (OR)=1.17, 95% confidence interval (CI)=1.01-1.36; TT vs. CC: adjusted OR=1.49, 95% CI=1.18-1.89; TT vs. CT/CC: adjusted OR=1.38, 95% CI=1.10-1.72]. Likely, rs873601 A allele also conferred increased CRC susceptibility. In contrast, a protective association was identified between rs751402 C>T polymorphism and the risk of CRC. In summary, our results indicated that these three polymorphisms were found to associate with CRC susceptibility in a Southern Chinese population.

  5. DNA repair gene XRCC4 codon 247 polymorphism modified diffusely infiltrating astrocytoma risk and prognosis.

    PubMed

    Lin, Zhong-Hui; Chen, Jin-Chun; Wang, Yun-Sun; Huang, Teng-Jiao; Wang, Jin; Long, Xi-Dai

    2013-12-27

    The DNA repair gene X-ray cross-complementary group 4 (XRCC4), an important caretaker of the overall genome stability, is thought to play a major role in human tumorigenesis. We investigated the association between an important polymorphic variant of this gene at codon 247 (rs373409) and diffusely infiltrating astrocytoma (DIA) risk and prognosis. This hospital-based case-control study investigated this association in the Guangxi population. In total, 242 cases with DIA and 358 age-, sex-, and race-matched healthy controls were genotyped using TaqMan-PCR technique. We found a significant difference in the frequency of XRCC4 genotypes between cases and controls. Compared with the homozygote of XRCC4 codon 247 Ala alleles (XRCC4-AA), the genotypes of XRCC4 codon 247 Ser alleles (namely XRCC4-AS or -SS) increased DIA risk (odds ratios [OR], 1.82 and 2.89, respectively). Furthermore, XRCC4 polymorphism was correlated with tumor dedifferentiation of DIA (r = 0.261, p < 0.01). Additionally, this polymorphism modified the overall survival of DIA patients (the median survival times were 26, 14, and 8 months for patients with XRCC4-AA, -AS, and -SS, respectively). Like tumor grade, XRCC4 codon 247 polymorphism was an independent prognostic factor influencing the survival of DIA. These results suggest that XRCC4 codon 247 polymorphism may be associated with DIA risk and prognosis among the Guangxi population.

  6. Interleukin-21 polymorphism affects gene expression and is associated with risk of ischemic stroke.

    PubMed

    Li, Guanggang; Xu, Ruxiang; Cao, Yinghua; Xie, Xiaodong; Zheng, Zhendong

    2014-12-01

    There has been more and more evidence to confirm the essential role of inflammatory processes in the development of ischemic stroke. Interleukin-21 (IL-21), the most recently discovered CD132-dependent cytokine, plays a key role in regulating inflammation. The aim of the study was to understand the association between IL-21 polymorphisms and ischemic stroke, and the effects of these polymorphisms on gene expression. Two polymorphisms in IL-21, rs907715G/A and rs4833837A/G, were identified in 278 ischemic stroke patients and 282 healthy controls. Results showed that frequencies of rs907715GA and AA genotypes were significantly increased in cases than in controls (odd ratio (OR) = 1.49, 95% confidence interval (CI): 1.01-2.14, P = 0.042; OR = 2.21, 95% CI: 1.38-3.53, P = 0.001). Similarly, rs907715A allele revealed a positive association with the disease (OR = 1.52, P = 0.001). The rs4833837A/G polymorphism did not show any correlation with ischemic stroke. We further evaluated IL-21 messenger RNA (mRNA) and protein levels in peripheral blood mononuclear cells (PBMCs) from subjects carrying different polymorphism genotypes. Results revealed that subjects carrying polymorphic rs907715GA and AA genotypes had significantly higher IL-21 mRNA levels, whereas protein level was increased only in subjects with rs907715AA genotype. Serum level of IL-21 was also significantly elevated in subjects with rs907715AA genotype. These data suggest that IL-21 polymorphism is associated with increased susceptibility to ischemic stroke possibly by upregulating gene expression.

  7. 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

  8. 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.

  9. 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

  10. Prion-like Doppel gene polymorphisms and scrapie susceptibility in Portuguese sheep breeds.

    PubMed

    Mesquita, P; Batista, M; Marques, M R; Santos, I C; Pimenta, J; Silva Pereira, M; Carolino, I; Santos Silva, F; Oliveira Sousa, M C; Gama, L T; Fontes, C M; Horta, A E M; Prates, J A M; Pereira, R M

    2010-06-01

    The establishment of an association between prion protein gene (PRNP) polymorphisms and scrapie susceptibility in sheep has enabled the development of breeding programmes to increase scrapie resistance in the European Union. Intense selection for PRNP genotype may lead to correlated selection for genes linked to PRNP. We intended to investigate if any association exists between genetic variation in prion-like protein Doppel gene (PRND) and scrapie susceptibility, determined through PRNP genotyping. Sampling included 460 sheep from eight Portuguese breeds and the PRND gene coding region was analysed by multiple restriction fragment-single strand conformation polymorphism (MRF-SSCP), whereas PRNP genotyping was carried out by primer extension. A synonymous substitution (c.78G>A) was detected in codon 26 of the PRND gene, in all breeds except Churra Mondegueira. Linkage disequilibrium was found between the PRND and PRNP loci (P = 0.000). Specifically, PRND was monomorphic in the 45 animals with the more resistant ARR/ARR PRNP genotype (P = 0.003), whereas a higher frequency of PRND heterozygotes (GA) was associated with ARQ/AHQ (P = 0.029). These results constitute preliminary evidence of an association between a polymorphism in the PRND gene and scrapie susceptibility, and indicate that the possibility of undesirable consequences from widespread selection for PRNP genotype on genetic diversity and reproduction traits needs to be further investigated.

  11. 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

  12. Polymorphisms in DNA Repair Genes and MDR1 and the Risk for Non-Hodgkin Lymphoma

    PubMed Central

    Kim, Hee Nam; Kim, Nan Young; Yu, Li; Kim, Yeo-Kyeoung; Lee, Il-Kwon; Yang, Deok-Hwan; Lee, Je-Jung; Shin, Min-Ho; Park, Kyeong-Soo; Choi, Jin-Su; Kim, Hyeoung-Joon

    2014-01-01

    The damage caused by oxidative stress and exposure to cigarette smoke and alcohol necessitate DNA damage repair and transport by multidrug resistance-1 (MDR1). To explore the association between polymorphisms in these genes and non-Hodgkin lymphoma risk, we analyzed 15 polymorphisms of 12 genes in a population-based study in Korea (694 cases and 1700 controls). Four genotypes of DNA repair pathway genes (XRCC1 399 GA, OGG1 326 GG, BRCA1 871 TT, and WRN 787 TT) were associated with a decreased risk for NHL [odds ratio (OR)XRCC1 GA = 0.80, p = 0.02; OROGG1 GG = 0.70, p = 0.008; ORBRCA1 TT = 0.71, p = 0.048; ORWRN TT = 0.68, p = 0.01]. Conversely, the MGMT 115 CT genotype was associated with an increased risk for NHL (OR = 1.25, p = 0.04). In the MDR1 gene, the 1236 CC genotype was associated with a decreased risk for NHL (OR = 0.74, p = 0.04), and the 3435 CT and TT genotypes were associated with an increased risk (OR3435CT = 1.50, p < 0.0001; OR3435TT = 1.43, p = 0.02). These results suggest that polymorphisms in the DNA repair genes XRCC1, OGG1, BRCA1, WRN1, and MGMT and in the MDR1 gene may affect the risk for NHL in Korean patients. PMID:24756092

  13. Polymorphisms in DNA repair genes and MDR1 and the risk for non-Hodgkin lymphoma.

    PubMed

    Kim, Hee Nam; Kim, Nan Young; Yu, Li; Kim, Yeo-Kyeoung; Lee, Il-Kwon; Yang, Deok-Hwan; Lee, Je-Jung; Shin, Min-Ho; Park, Kyeong-Soo; Choi, Jin-Su; Kim, Hyeoung-Joon

    2014-04-21

    The damage caused by oxidative stress and exposure to cigarette smoke and alcohol necessitate DNA damage repair and transport by multidrug resistance-1 (MDR1). To explore the association between polymorphisms in these genes and non-Hodgkin lymphoma risk, we analyzed 15 polymorphisms of 12 genes in a population-based study in Korea (694 cases and 1700 controls). Four genotypes of DNA repair pathway genes (XRCC1 399 GA, OGG1 326 GG, BRCA1 871 TT, and WRN 787 TT) were associated with a decreased risk for NHL [odds ratio (OR)XRCC1 GA=0.80, p=0.02; OROGG1 GG=0.70, p=0.008; ORBRCA1 TT=0.71, p=0.048; ORWRN TT=0.68, p=0.01]. Conversely, the MGMT 115 CT genotype was associated with an increased risk for NHL (OR=1.25, p=0.04). In the MDR1 gene, the 1236 CC genotype was associated with a decreased risk for NHL (OR=0.74, p=0.04), and the 3435 CT and TT genotypes were associated with an increased risk (OR3435CT=1.50, p<0.0001; OR3435TT=1.43, p=0.02). These results suggest that polymorphisms in the DNA repair genes XRCC1, OGG1, BRCA1, WRN1, and MGMT and in the MDR1 gene may affect the risk for NHL in Korean patients.

  14. The association between polymorphisms in the PDCD1 gene and the risk of cancer

    PubMed Central

    Zhang, Jie; Zhao, Taiqiang; Xu, Chengjie; Huang, Jiang; Yu, Hua

    2016-01-01

    Abstract Background: The effects of the programed cell death 1 (PDCD1) gene polymorphisms on cancer risk have been investigated in some studies; however, the results were conflicting and ambiguous. Therefore, we aimed to do a meta-analysis to investigate the association of PDCD1 polymorphisms with cancer risk from all eligible case–control studies. Materials and methods: An electronic search of the PubMed, Embase, Chinese National Knowledge Infrastructure, and Wanfang databases was performed. The association between PDCD1 polymorphisms with cancer risk was calculated with odds ratios (ORs) and their corresponding 95% of confidence intervals (CIs). Results: A total of 24 case–control studies from 13 articles that investigated the associations of 5 widely studied polymorphisms in PDCD1 gene and cancer risks were included. The results of meta-analysis: the PDCD-1.5 (rs2227981) and PDCD-1.3 (rs11568821) polymorphisms were associated with decreased risk of cancer (rs2227981: OR = 0.75, 95% CI: 0.64–0.86, P < 0.0001 for TT vs TC + CC; rs11568821: OR = 0.79, 95% CI: 0.65–0.96, P = 0.02 for TC vs TT), while no significant associations were found for the other 3 polymorphisms (PDCD-1.9 [rs2227982] polymorphism: OR = 1.03, 95% CI: 0.90–1.18, P = 0.66 for CC + TC vs TT; PDCD1 rs7421861 polymorphism: OR = 1.10, 95% CI: 0.96–1.25, P = 0.16 for CC + TC vs TT; PDCD-1.6 [rs10204525] polymorphism: OR = 0.93, 95% CI: 0.82–1.05, P = 0.24 for GG + GA vs AA). Conclusion: The meta-analysis suggests that the PDCD-1.5 (rs2227981) and PDCD-1.3 (rs11568821) polymorphisms are associated with susceptibility of cancer. Further studies with larger sample sizes are required to make a better assessment of the above association. PMID:27749524

  15. 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

  16. 5-Hydroxytryptamine 2A receptor signaling cascade modulates adiponectin and plasminogen activator inhibitor 1 expression in adipose tissue.

    PubMed

    Uchida-Kitajima, Shoko; Yamauchi, Toshimasa; Takashina, Youko; Okada-Iwabu, Miki; Iwabu, Masato; Ueki, Kohjiro; Kadowaki, Takashi

    2008-09-01

    Knowledge of the regulatory factors associated with down-regulation of adiponectin gene expression and up-regulation of PAI-1 gene expression is crucial to understand the pathophysiological basis of obesity and metabolic diseases, and could establish new treatment strategies for these conditions. We showed that expression of 5-HT(2A) receptors was up-regulated in hypertrophic 3T3-L1 adipocytes, which exhibited decreased expression of adiponectin and increased expression of PAI-1. 5-HT(2A) receptor antagonists and suppression of 5-HT(2A) receptor gene expression enhanced adiponectin expression. Activation of Gq negatively regulated adiponectin expression, and inhibition of mitogen-activated protein kinase reversed the Gq-induced effect. Moreover, the 5-HT(2A) receptor blockade reduced PAI-1 expression. These findings indicate that antagonism of 5-HT(2A) receptors in adipocytes could improve the obesity-linked decreases in adiponectin expression and increases in PAI-1 expression.

  17. Association between vitamin D receptor (VDR) gene polymorphisms and systemic lupus erythematosus in Portuguese patients.

    PubMed

    Carvalho, C; Marinho, A; Leal, B; Bettencourt, A; Boleixa, D; Almeida, I; Farinha, F; Costa, P P; Vasconcelos, C; Silva, B M

    2015-07-01

    Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown origin, in which both genetic and environmental factors are involved. One such environmental factor is vitamin D, a vital hormone that plays a specific function in the immune system homeostasis, acting through a nuclear receptor (VDR) expressed in all immune cells. Several polymorphisms of the gene that encodes this receptor have been described. Though inconsistently, these polymorphisms have been associated with clinical manifestations and SLE development.The aim of this study was to determine the possible association between VDR gene polymorphisms (BsmI, ApaI, TaqI e FokI) and SLE susceptibility and severity, in a cohort of lupus patients from the north of Portugal.A total of 170 patients (F = 155, M = 15; age = 45 ± 13.4 years) with SLE (diagnosed according the American College of Rheumatology criteria) with at least five years of disease evolution and followed in the Autoimmune Disease Clinical Immunology Unit of Centro Hospitalar do Porto were studied. Patients and 192 ethnicity-matched controls were genotyped for BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236) and FokI (rs2228570) polymorphisms by TaqMan allelic discrimination assay. Disease severity was assessed by SLICC damage score, number of affected organs, number of severe flares and pharmacological history.SLE patients with the CT genotype of FokI polymorphism have a higher SLICC value (p = 0.031). The same result was observed for the group of patients with the TT genotype of TaqI polymorphism (p = 0.046). No differences were observed in VDR genotype between patients and controls. Also, we observed that the other clinical features analysed were not influenced by VDR polymorphisms.Our study confirms a possible role of VDR gene polymorphisms in SLE. A positive association was found between VDR polymorphisms and SLE severity (chronic damage). The presence of CT genotype of FokI and TT genotype of Taq

  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.

  19. 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.

  20. 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

  1. Polymorphism analysis in estrogen receptors alpha and beta genes and their association with infertile population in Pakistan

    PubMed Central

    Liaqat, Sinha; Hasnain, Shahida; Muzammil, Saima; Hayat, Sumreen

    2015-01-01

    Studies on polymorphism of estrogen receptor (ESR) alpha and beta genes have been mostly implicated in infertility, but the results have been controversial due to lack of comprehensive data. The present study focused on association of ESR genes with both male and female infertility. In ESRα, PvuII (rs2234693) and XbaI (rs9340799) were studied while in ESRβ gene, risk of infertility was determined for silent G/A RsaI (rs1256049) polymorphism. Total 124 subjects (74 cases and 50 controls) were part of this study having primary infertility. Restriction fragment length polymorphism (RFLP) was performed with PvuII, XbaI and RsaI to determine polymorphism. Correlation between age and follicle stimulating hormone (FSH) of cases and controls was determined and no association was found between infertility and FSH hormone. Heterozygous AG genotype of XbaI polymorphism (P= 2.505e-06) and heterozygous TC genotype (P= 0.00003) in PvuII polymorphism were strongly associated with risk of infertility. In ESRβ gene, there was lack of polymorphism for RsaI in our population as all subjects were homozygous (GG). Haplotype frequencies showed that XbaI and PvuII polymorphisms are in strong linkage disequilibrium. This study shows that in our population XbaI and PvuII polymorphisms of ESRα are associated with risk of infertility. PMID:27065769

  2. K153R polymorphism in myostatin gene increases the rate of promyostatin activation by furin.

    PubMed

    Szláma, György; Trexler, Mária; Buday, László; Patthy, László

    2015-01-30

    Recent studies demonstrated an association between the K153R polymorphism in the myostatin gene with extreme longevity, lower muscle strength and obesity but the molecular basis of these associations has not been clarified. Here, we show that the K153R mutation significantly increases the rate of proteolysis of promyostatin by furin, but has no effect on the activity of the latent complex or the cleavage of the latent complex by bone morphogenetic protein 1 (BMP-1). The increased rate of activation of K153R mutant promyostatin may explain why this polymorphism is associated with obesity, lower muscle strength and extension of lifespan.

  3. Doppel gene polymorphisms in Portuguese sheep breeds: insights on ram fertility.

    PubMed

    Pereira, R M; Mesquita, P; Batista, M; Baptista, M C; Barbas, J P; Pimenta, J; Santos, I C; Marques, M R; Vasques, M I; Silva Pereira, M; Santos Silva, F; Oliveira Sousa, M C; Fontes, C M G; Horta, A E M; Prates, J A M; Marques, C C

    2009-08-01

    Transgenic knockout of the gene encoding the prion-like protein Doppel leads to male infertility in mice. The precise role of Doppel in male fertility is still unclear, but sperm from Doppel-deficient mice appear to be unable to undergo the normal acrosome reaction necessary to penetrate the zona pellucida of the oocyte. The objective of this study was to characterize Doppel (Prnd) gene polymorphisms in eight Portuguese sheep breeds and to determine a possible relationship between these polymorphisms and ram fertility. Ovine genomic DNA of 364 animals of different breeds (Bordaleira entre Douro e Minho, Churra Badana, Churra Galega Mirandesa, Churra Mondegueira, Merino da Beira Baixa, Merino Branco, Saloia and Serra da Estrela) were analysed by multiple restriction fragment-single-strand conformation polymorphism (MRF-SSCP). This analysis revealed a synonymous substitution G-->A in codon 26 of Prnd gene. Churra Galega Mirandesa and Saloia breeds were more polymorphic (P=0.005 and P=0.04, respectively) than the overall population, while Serra da Estrela and Merino Branco animals were less polymorphic (P=0.007 and P=0.04). No polymorphism was found in Churra Mondegueira breed. Semen from 11 rams of Churra Galega Mirandesa breed (7 homozygous wildtype GG and 4 heterozygous GA) routinely used in the Portuguese Animal Germoplasm Bank was collected and frozen for fertility tests. A classification function was estimated, using data from post-swim-up semen motility and concentration and Day 6 embryo production rate, allowing the identification of the Doppel homozygous GG genotype with 86.7% of accuracy. This preliminary study detected the presence of only one polymorphism in codon 26 of Prnd gene in the Portuguese sheep breeds. In the polymorphic Churra Galega Mirandesa breed, GG genotype could be characterized through a model using three fertility traits, suggesting a relationship with male reproduction. Any future research should investigate not only AA genotype and its

  4. Angiotensin I - Converting Enzyme Gene Polymorphism and Activity in Patients with Ischemic Stroke

    PubMed Central

    Stankovic, Aleksandra; Asanin, Milika; Jovanovic-Markovic, Zagorka; Alavantic, Dragan; Majkic-Singh, Nada

    2011-01-01

    The possible association of ACE polymorphism with ischemic stroke (IS) was evaluated in 65 patients with IS and 330 age and BMI-matched controls. ACE genotypes were determined by polymerase chain reaction (PCR). There was no significant difference in ACE genotype/allele frequencies between case and control group (p>0.05). Patients with D allele had 4,7 times higher risk for large vessel IS than healthy persons D allele possessors. Persons with D allele had 9.2 times higher risk for large vessel disease than small vessel disease. These data suggest a possible association of ACE gene polymorphism with pathogenesis of large vessel IS.

  5. [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

  6. Genetic and Molecular Basis of QTL of Diabetes in Mouse: Genes and Polymorphisms

    PubMed Central

    Gao, Peng; Jiao, Yan; Xiong, Qing; Wang, Cong-Yi; Gerling, Ivan; Gu, Weikuan

    2008-01-01

    A systematic study has been conducted of all available reports in PubMed and OMIM (Online Mendelian Inheritance in Man) to examine the genetic and molecular basis of quantitative genetic loci (QTL) of diabetes with the main focus on genes and polymorphisms. The major question is, What can the QTL tell us? Specifically, we want to know whether those genome regions differ from other regions in terms of genes relevant to diabetes. Which genes are within those QTL regions, and, among them, which genes have already been linked to diabetes? whether more polymorphisms have been associated with diabetes in the QTL regions than in the non-QTL regions. Our search revealed a total of 9038 genes from 26 type 1 diabetes QTL, which cover 667,096,006 bp of the mouse genomic sequence. On one hand, a large number of candidate genes are in each of these QTL; on the other hand, we found that some obvious candidate genes of QTL have not yet been investigated. Thus, the comprehensive search of candidate genes for known QTL may provide unexpected benefit for identifying QTL genes for diabetes. PMID:19471607

  7. Cloning of TPO gene and associations of polymorphisms with chicken growth and carcass traits.

    PubMed

    Hou, Xinyan; Han, Ruili; Tian, Yadong; Xie, Wanying; Sun, Guirong; Li, Guoxi; Jiang, Ruirui; Kang, Xiangtao

    2013-04-01

    Thyroid peroxidase (TPO), which located on the apical membrane surface of thyrocytes, is the key enzyme involved in thyroid hormone synthesis, mainly catalyses the iodination of tyrosine residues and the coupling of iodotyrosines on thyroglobulin to form thyroxine and triiodothyronine. The objectives of this study were to identify genetic polymorphisms of the chicken TPO gene and to analyze potential association between single nucleotide polymorphisms (SNPs) and growth and carcass traits in chicken. Partial sequences of TPO gene were cloned firstly. The nucleotide sequence was found to have 72 % identity with that of humans. The chicken TPO amino acid sequence was 71 %. Through polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing methods, three novel mutations of the chicken TPO gene were detected in the F2 resource population from Gushi chickens and Anka broilers. The association analysis indicated that all of the three SNPs showed association with chicken growth at different periods. The g.29996C>T polymorphisms was significantly associated with body weight, breast bone length, pectoral angle at 12 weeks, claw weight and leg muscle weight (P < 0.05). In addition, individuals with the TT genotype had higher value for almost all the traits than CC and CT genotype. Meanwhile for CLW, the additive effects were significant (P < 0.05). Hence, we suggest that genotype TT can be regarded as a potential molecular marker for later growth and carcass traits in chicken.

  8. Vitamin D receptor (VDR) gene polymorphisms and susceptibility to systemic lupus erythematosus clinical manifestations.

    PubMed

    de Azevêdo Silva, J; Monteiro Fernandes, K; Trés Pancotto, J A; Sotero Fragoso, T; Donadi, E A; Crovella, S; Sandrin-Garcia, P

    2013-10-01

    Systemic lupus erythematosus (SLE) is an autoimmune disorder with heterogeneous clinical manifestations and target tissue damage. Currently, several genes have been associated with SLE susceptibility, including vitamin D receptor (VDR), which is a mediator of immune responses through the action of vitamin D. Polymorphisms in the VDR gene can impair the vitamin D (D3) function role, and since SLE patients show deficient D3 blood levels, it leads to a possible connection to the disease's onset. In our study we searched for an association between VDR polymorphisms and risk of developing SLE, as well as the disease's clinical manifestations. We enrolled 158 SLE patients and 190 Southeast Brazilian healthy controls, genotyped for five Tag single nucleotide polymorphisms (SNPs), covering most of the VDR gene region. We found an association between VDR SNPs and SLE for the following clinical manifestations: rs11168268 and cutaneous alterations (p=0.036), rs3890733 (p=0.003) rs3890733 and arthritis (p=0.001), rs2248098 and immunological alterations (p=0.040), rs4760648 and antibody anti-dsDNA (p=0.036). No association was reported between VDR polymorphisms and SLE susceptibility.

  9. Analysis of DRB3 gene polymorphisms in Jafarabadi, Mediterranean, and Murrah buffaloes from Brazil.

    PubMed

    Stafuzza, N B; Olivatto, L M; Naressi, B C M; Tonhati, H; Amaral-Trusty, M E J

    2016-01-01

    The DRB3 gene is an MHC class II gene that has a high degree of polymorphism with more than 100 alleles described in cattle. This variation contributes to differences among individuals in immune responsiveness and disease resistance. In this study, we searched for allelic variants in exon 2 of the DRB3 gene in 80 river buffaloes of three breeds in Brazil using a PCR-RFLP technique. The PCR product showed genetic polymorphism when digested with RsaI, PstI or HaeIII restriction enzymes. In total, 16 restriction patterns were identified: nine restriction patterns and 16 genotypes were found with RsaI; four restriction patterns and nine genotypes were found with HaeIII; and, three restriction patterns and four genotypes were found with PstI. Three RFLP patterns were exclusive to Jafarabadi buffaloes (RsaI-b, RsaI-c and RsaI-f) and three others were only observed in Mediterranean buffaloes (RsaI-g, RsaI-h and PstI-y). Jafarabadi buffaloes had a larger number of RFLP patterns than Mediterranean and Murrah breeds. The analysis showed that the DRB3 exon 2 was highly polymorphic, with the highest degree of polymorphism in Mediterranean buffaloes. This study provides the first assessment of allelic variation among three different buffalo breeds from Brazil and provides a basis for further investigations into the association between the DRB3 alleles and disease resistance. PMID:27051015

  10. The analysis of BDNF gene polymorphism haplotypes and impulsivity in methamphetamine abusers.

    PubMed

    Su, Hang; Tao, Jingyan; Zhang, Jie; Xie, Ying; Han, Bin; Lu, Yuling; Sun, Haiwei; Wei, Youdan; Wang, Yue; Zhang, Yu; Zou, Shengzhen; Wu, Wenxiu; Zhang, Jiajia; Xu, Ke; Zhang, Xiangyang; He, Jincai

    2015-05-01

    An increasing number of evidence showed that genetic factors might contribute to drug abuse vulnerability. Data from genetic scans in humans suggest that brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, may be associated with substance abuse or dependence. To test the hypothesis that the BDNF gene polymorphism is involved in methamphetamine abuse, we compared three single nucleotide polymorphisms (SNPs, rs16917204, rs16917234, and rs2030324) of the BDNF gene in 200 methamphetamine abusers and 219 healthy individuals. We also considered the association of these polymorphisms with impulsivity in methamphetamine abusers using Barratt Impulsivity Scale-11(BIS-11) Chinese version. Individual SNP analysis showed no significant differences in genotype and allele distributions between the methamphetamine abusers and controls. Haplotype analysis of rs16917204-rs16917234-rs2030324 revealed that a major C-C-T haplotype was significantly associated a lower odds of methamphetamine abuse, even after Bonferroni correction. Within the methamphetamine-abuse group, subjects carrying the T allele of rs2030324 genotype had significantly higher motor impulsivity scores of BIS compared to those with the C/C genotype. Our findings suggest that the BDNF gene polymorphism may contribute to the impulsivity in methamphetamine abusers.

  11. Single nucleotide polymorphisms of the FTO gene and cancer risk: an overview.

    PubMed

    Hernández-Caballero, Marta Elena; Sierra-Ramírez, José Alfredo

    2015-03-01

    The FTO (fat mass and obesity-associated) gene has a strong linkage disequilibrium block, within which SNPs have been identified that are involved in the development of obesity. Recently some of these variants have also been associated with cancer. However, identification of the possible mechanisms that could explain these associations has proven to be elusive. It has been found that FTO polymorphisms can regulate the expression of genes at large kilobases of distance as well as the expression of the FTO gene itself, and regions for transcription factor binding. To date it has been observed that variants rs9939609, rs17817449, rs8050136, rs1477196, rs6499640, rs16953002, rs11075995 and rs1121980 are associated with the risk of developing cancer. Some studies have produced negative results when comparing the same polymorphisms, but make a simple association between polymorphic variants and cancer, have proved difficult because this relation is by nature multifactorial. A certain degree of variation resulting from the improper design of studies or processing of data can lead to erroneous conclusions. However, it is now unquestionable that certain FTO polymorphisms regulate genetic expression related to cancer susceptibility, although this field is just beginning to be understood.

  12. Spontaneous abortion and functional polymorphism (Val16Ala) in the manganese SOD gene.

    PubMed

    Eskafi Sabet, E; Salehi, Z; Khodayari, S; Sabouhi Zarafshan, S; Zahiri, Z

    2015-02-01

    Spontaneous abortion is the most common complication of early pregnancy. Genetic factors have been hypothesised to play a role in spontaneous abortion. Since it is possible that the balance of oxidants and antioxidants can be affected by different genetic variants, gene polymorphisms have been proposed as a susceptibility factor that increases the chance of miscarriage. Manganese superoxide dismutase is an important antioxidant enzyme encoded by manganese superoxide dismutase (MnSOD) gene. The aim of this experiment was to assess whether Val16Ala polymorphism of MnSOD gene is associated with miscarriage in northern Iran. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for genotyping. Statistical analyses were conducted using the χ(2)-test. The genetic distributions did not differ significantly between cases and controls, however slightly more Val/Val genotypes were found among the patients compared with control subjects (p = 0.059). No correlation was observed between susceptibility to abortion and MnSOD Val16Ala polymorphism. Larger population-based studies are needed for clarifying the relationship between abortion and MnSOD genotypes.

  13. In silico analysis of polymorphisms in microRNAs that target genes affecting aerobic glycolysis

    PubMed Central

    Venkatesh, Thejaswini; Tsutsumi, Rie

    2016-01-01

    Background Cancer cells preferentially metabolize glucose through aerobic glycolysis, an observation known as the Warburg effect. Recently, studies have deciphered the role of oncogenes and tumor suppressor genes in regulating the Warburg effect. Furthermore, mutations in glycolytic enzymes identified in various cancers highlight the importance of the Warburg effect at the molecular and cellular level. MicroRNAs (miRNAs) are non-coding RNAs that posttranscriptionally regulate gene expression and are dysregulated in the pathogenesis of various types of human cancers. Single nucleotide polymorphisms (SNPs) in miRNA genes may affect miRNA biogenesis, processing, function, and stability and provide additional complexity in the pathogenesis of cancer. Moreover, mutations in miRNA target sequences in target mRNAs can affect expression. Methods In silico analysis and cataloguing polymorphisms in miRNA genes that target genes directly or indirectly controlling aerobic glycolysis was carried out using different publically available databases. Results miRNA SNP2.0 database revealed several SNPs in miR-126 and miR-25 in the upstream and downstream pre-miRNA flanking regions respectively should be inserted after flanking regions and miR-504 and miR-451 had the fewest. These miRNAs target genes that control aerobic glycolysis indirectly. SNPs in premiRNA genes were found in miR-96, miR-155, miR-25 and miR34a by miRNASNP. Dragon database of polymorphic regulation of miRNA genes (dPORE-miRNA) database revealed several SNPs that modify transcription factor binding sites (TFBS) or creating new TFBS in promoter regions of selected miRNA genes as analyzed by dPORE-miRNA. Conclusions Our results raise the possibility that integration of SNP analysis in miRNA genes with studies of metabolic adaptations in cancer cells could provide greater understanding of oncogenic mechanisms. PMID:27004216

  14. Association of phosphodiesterase 4D gene and interleukin-6 receptor gene polymorphisms with ischemic stroke in a Chinese hypertensive population.

    PubMed

    Song, H J; Zhou, X H; Guo, L; Tian, F L; Guo, X F; Sun, Y X

    2015-12-29

    Genetic factors have been shown to be associated with the risk of stroke. However, due to individual differences, the extent of the association between genetic factors and stroke varies widely. Hypertension is considered one of the most important risk factors for stroke, but it remains unknown whether the genetic association with stroke in a hypertensive population is the same as that in a non-hypertensive population. The aim of the present study was to explore the association between the phosphodiesterase 4D gene (PDE4D) and interleukin-6 receptor gene (IL6R) single nucleotide polymorphisms and ischemic stroke in a hypertensive population. The study included 307 ischemic stroke cases with hypertension and 227 controls (simple hypertension). The polymorphic loci rs12188950 and rs918592 in PDE4D, and rs4075015 and rs4537545 in IL6R were selected for analyzing the genotype and allele frequencies between cases and controls. rs12188950 was not found in the study population. In the univariate analysis, the rs918592 polymorphism in PDE4D was found to be significantly associated with ischemic stroke with the recessive model (P = 0.02), whereas no association with ischemic stroke was observed for rs4075015 and rs4537545 in IL6R. Following adjustment for binary logistic regression, the rs918592 polymorphism was not found to be associated with ischemic stroke. While prior studies have found an association between PDE4D and IL6R polymorphisms and ischemic stroke, our results suggest that this association may be different in a hypertensive population. Therefore, the association between PDE4D and IL6R polymorphisms and ischemic stroke among a hypertensive population requires further investigation.

  15. [The correlations between polymorphism of growth hormone receptor gene and butcher traits in rabbit].

    PubMed

    Deng, Xiao-Song; Wan, Jie; Chen, Shi-Yi; Wang, Yan; Lai, Song-Jia; Jiang, Mei-Shan; Xu, Min

    2008-11-01

    Five rabbit populations (Belgian hare, Tianfu black rabbit, Great line of Zika rabbit, Harbin white rabbit, and California rabbit) were used to analyze the polymorphism of growth hormone receptor (GHR) gene by PCR-SSCP. Results indicated that there were two mutation sites (C705T and C810T) in the 5 populations. The least square analyses showed that the live weight, visceraste weight, and slaughter percentage of AA and MM genotypes were significantly lower than BB and NN genotypes (P<0.05). In contrast, the GHR polymorphism had no significant difference for least squares means of feed transformation efficiency (P>0.05). It suggested that GHR gene may be a candidate gene responsible for butcher trait in rabbit.

  16. 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

  17. 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

  18. DNA polymorphism analysis of candidate genes for type 2 diabetes mellitus in a Mexican ethnic group.

    PubMed

    Flores-Martínez, S E; Islas-Andrade, S; Machorro-Lazo, M V; Revilla, M C; Juárez, R E; Mújica-López, K I; Morán-Moguel, M C; López-Cardona, M G; Sánchez-Corona, J

    2004-01-01

    Type 2 diabetes mellitus is a complex metabolic disorder resulting from the action and interaction of many genetic and environmental factors. It has been reported that polymorphisms in genes involved in the metabolism of glucose are associated with the susceptibility to develop type 2 diabetes mellitus. Although the risk of developing type 2 diabetes mellitus increases with age, as well as with obesity and hypertension, its prevalence and incidence are different among geographical regions and ethnic groups. In Mexico, a higher prevalence and incidence has been described in the south of the country, and differences between urban and rural communities have been observed. We studied 73 individuals from Santiago Jamiltepec, a small indigenous community from Oaxaca State, Mexico. This population has shown a high prevalence of type 2 diabetes mellitus, and the aim of this study was to analyze the relationship between the Pst I (insulin gene), Nsi I (insulin receptor gene) and Gly972Arg (insulin receptor substrate 1 gene) polymorphisms and type 2 diabetes mellitus, obesity and hypertension in this population. Clinical evaluation consisted of BMI and blood pressure measurements, and biochemical assays consisted of determination of fasting plasma insulin and glucose levels. PCR and restriction enzyme digestion analysis were applied to genomic DNA to identify the three polymorphisms. From statistical analysis carried out here, individually, the Pst I, Nsi I and Gly972Arg polymorphisms were not associated with the type 2 diabetes, obese or hypertensive phenotypes in this population. Nevertheless, there was an association between the Nsi I and Pst I polymorphisms and increased serum insulin levels.

  19. Streptomycin Resistance and Lineage-Specific Polymorphisms in Mycobacterium tuberculosis gidB Gene

    PubMed Central

    Spies, Fernanda S.; Ribeiro, Andrezza W.; Ramos, Daniela F.; Ribeiro, Marta O.; Martin, Anandi; Palomino, Juan Carlos; Rossetti, Maria Lucia R.; da Silva, Pedro Eduardo A.; Zaha, Arnaldo

    2011-01-01

    Mutations related to streptomycin resistance in the rpsL and rrs genes are well known and can explain about 70% of this phenotypic resistance. Recently, the gidB gene was found to be associated with low-level streptomycin resistance in Mycobacterium tuberculosis. Mutations in gidB have been reported with high frequency, and this gene appears to be very polymorphic, with frameshift and point mutations occurring in streptomycin-susceptible and streptomycin-resistant strains. In this study, mutations in gidB appeared in 27% of streptomycin-resistant strains that contained no mutations in the rpsL or rrs genes, and they were associated with low-level streptomycin resistance. However, the association of certain mutations in gidB with streptomycin resistance needs to be further investigated, as we also found mutations in gidB in streptomycin-susceptible strains. This occurred only when the strain was resistant to rifampin and isoniazid. Two specific mutations appeared very frequently in this and other studies of streptomycin-susceptible and -resistant strains; these mutations were not considered related to streptomycin resistance, but as a polymorphism. We stratified the strains according to the different phylogenetic lineages and showed that the gidB16 polymorphism (16G allele) was exclusively present in the Latin American-Mediterranean (LAM) genotype, while the gidB92 polymorphism (92C allele) was associated with the Beijing lineage in another population. In the sample studied, the two characterized single-nucleotide polymorphisms could distinguish LAM and Beijing lineages from the other lineages. PMID:21593257

  20. 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

  1. Endothelial nitric oxide synthase (eNOS) gene polymorphism in early term chronic allograft nephropathy.

    PubMed

    Yilmaz, E; Mir, S; Berdeli, A

    2009-12-01

    Chronic allograft nephropathy (CAN) is a complex phenomenon caused by underlying kidney disease with superimposed enviromental and genetic factors. CAN development begins with progressive renal microvascular injury. Endothelial cells play key roles in the regulation of vascular tone, permeability, and remodeling. A reduction in basal nitric oxide (NO) release as a result of genetic variation in endothelial NO synthase (eNOS) function may predispose to hypertension, thrombosis, vasospasm, and atherosclerosis, all contributing to the development of CAN. We analyzed the G894T mutation at exon 7 of the eNOS gene in relationship to CAN among 81 children with renal transplantations. The 20 patients who developed CAN underwent renal biopsies for histological confirmation. Proteinuria and hypertension were observed in CAN. We selected 173 healthy reference subjects. The G894T polymorphism of the eNOS gene was determined by PCR-restriction fragment-length polymorphism analysis. The group included 33 male and 48 female subjects who received 32 living-related grafts and 49 from deceased donors (DD) donors. Donor age (y) was 32.7 +/- 13.7 and the HLA A,B,DR mismatch number of the cadaveric cases was 3.5 +/- 0.79. The distribution of the genotypes were ENOS GG/GT/TT 48%, 33%, 19%, respectively. G-alleles frequency was 64.8%; T-allele frequency was 35.2%. ENOS G894T gene polymorphism did not seem to influence long-term renal allograft outcome. Recipient ENOS G894T gene polymorphism did not alter the risk of chronic allograft failure. Even if NO synthesis and bioactivity are influenced by this polymorphism, many vasoactive factors may have roles to suppress the advantageous effects of NO. PMID:20005399

  2. Adiponectin Lowers Glucose Production by Increasing SOGA

    PubMed Central

    Cowerd, Rachael B.; Asmar, Melissa M.; Alderman, J. McKee; Alderman, Elizabeth A.; Garland, Alaina L.; Busby, Walker H.; Bodnar, Wanda M.; Rusyn, Ivan; Medoff, Benjamin D.; Tisch, Roland; Mayer-Davis, Elizabeth; Swenberg, James A.; Zeisel, Steven H.; Combs, Terry P.

    2010-01-01

    Adiponectin is a hormone that lowers glucose production by increasing liver insulin sensitivity. Insulin blocks the generation of biochemical intermediates for glucose production by inhibiting autophagy. However, autophagy is stimulated by an essential mediator of adiponectin action, AMPK. This deadlock led to our hypothesis that adiponectin inhibits autophagy through a novel mediator. Mass spectrometry revealed a novel protein that we call suppressor of glucose by autophagy (SOGA) in adiponectin-treated hepatoma cells. Adiponectin increased SOGA in hepatocytes, and siRNA knockdown of SOGA blocked adiponectin inhibition of glucose production. Furthermore, knockdown of SOGA increased late autophagosome and lysosome staining and the secretion of valine, an amino acid that cannot be synthesized or metabolized by liver cells, suggesting that SOGA inhibits autophagy. SOGA decreased in response to AICAR, an activator of AMPK, and LY294002, an inhibitor of the insulin signaling intermediate, PI3K. AICAR reduction of SOGA was blocked by adiponectin; however, adiponectin did not increase SOGA during PI3K inhibition, suggesting that adiponectin increases SOGA through the insulin signaling pathway. SOGA contains an internal signal peptide that enables the secretion of a circulating fragment of SOGA, providing a surrogate marker for intracellular SOGA levels. Circulating SOGA increased in parallel with adiponectin and insulin activity in both humans and mice. These results suggest that adiponectin-mediated increases in SOGA contribute to the inhibition of glucose production. PMID:20813965

  3. Cloning and polymorphisms of the 3' untranslated region of malic enzyme gene in Chinese red cattle.

    PubMed

    Zhou, G L; Zhang, G L; Cao, Y; Jin, H G

    2011-09-01

    The objective of this study was to identify alternative transcripts and single nucleotide polymorphisms (SNPs) in the 3'-untranslated region (3' UTR) of bovine malic enzyme (ME1) gene and to evaluate the extent to which polymorphisms were associated with meat quality and carcass traits in Chinese red cattle. Two transcripts, long transcript and short transcript that differ in the length of the 3' UTR were cloned. A single nucleotide polymorphism was detected in 3' UTR and a restriction site for endonuclease ME1-Dra I was also found. The result revealed that the ME1-Dra I genotypes had a significant effect on cooking loss, pH measured 24h post-mortem (pH(24h)) and eye muscle area (P < 0.05). In conclusion, the SNPs may be used as DNA markers to select for meat quality and carcass traits in Chinese red cattle.

  4. 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

  5. The Association Between Viral Infections and Co-stimulatory Gene Polymorphisms in Kidney Transplant Outcomes

    PubMed Central

    Niknam, Ahmad; Karimi, Mohammad Hossein; Yaghobi, Ramin; Geramizadeh, Bita; Roozbeh, Jamshid; Salehipour, Mehdi; Iravani, Mahdiyar

    2016-01-01

    Background The surveillance of kidney transplant patients depends on function of different immunologic markers like co-stimulatory molecules. These molecules may also be associated with post kidney transplant viral related outcomes. Objectives The aim of this study was to investigate the possible associations between co-stimulatory molecule gene polymorphisms and viral infections in kidney transplant patients. Patients and Methods In total, 172 kidney transplant patients were included in this study. Single nucleotide polymorphisms in loci of co-stimulatory molecules including: PDCD.1, CD28, CTLA4 and ICOS, were analyzed in the studied patients by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Active Cytomegalovirus (CMV) infection and history of hepatitis C virus (HCV) infection were analyzed in each kidney transplant patient using the CMV antigenemia kit and HCV antibody assay, according to the manufacturer’s instructions. Results CMV active infection was found in 31 of 172 (18.02%) kidney transplant patients. HCV infection was only found in two of the 172 (1.16%) studied patients. Significant associations were found between TT and TC genotypes of CTLA4 -1722T/C and T allele with acute rejection in CMV infected kidney transplant patients. A significant association was also found between the T allele of CD28 + 17 C/T genetic polymorphism and acute rejection in CMV infected kidney transplant patients. Significantly higher frequency of AA genotype and A allele of CTLA4 + 49AG polymorphism were found in CMV infected female patients. Also a significantly higher frequency of GG genotype and G allele of PDCD-1.3A/G polymorphisms were found in CMV infected female patients. Conclusions Based on these results, CTLA4 and CD28 genetic polymorphisms, which regulate T-cell activation, can influence active CMV infection in kidney transplant patients. These results should be confirmed by further investigations. PMID:27800130

  6. Inflammation-related cytokine gene polymorphisms in Behçet’s disease

    PubMed Central

    Al-Okaily, Fahda; Arfin, Misbahul; Al-Rashidi, Seham; Al-Balawi, Maysoon; Al-Asmari, Abdulrahman

    2015-01-01

    Behçet’s disease (BD) is a complex, multisystemic inflammatory disorder of unclear etiology. Single nucleotide polymorphisms in tumor necrosis factor (TNF) and interleukin (IL)-10 genes have been implicated in susceptibility to BD with inconsistent results in several ethnic populations. The aim of this case-control study was to evaluate the association of TNF-α (−308G/A), TNF-β (+252A/G), and IL-10 (−1082G/A, −819C/T, and −592 C/A) polymorphisms with susceptibility of BD in Saudi patients. Molecular genotyping of TNF-α, TNF-β, and IL-10 gene polymorphisms was performed to analyze the alleles and genotypes distribution in 272 Saudi subjects, including BD patients (61) and healthy controls (211). The frequencies of allele A and genotype GA of TNF-α (−308G/A) were significantly higher, whereas those of allele G and genotypes GG were significantly lower in BD patients than controls, indicating that A allele and GA genotype are susceptible, while G allele and GG genotype may be refractory to BD. The distribution of frequencies of alleles and genotype of TNF-β (+252A/G) promoter polymorphism was not significantly different between BD patients and healthy controls. Genotypes 1082GG, −819TT, and 592AA of IL-10 polymorphisms are significantly associated with susceptibility risk of BD, while genotypes 1082AA, 1082GA, 819CC, 819CT, 592CC, and 592CA are resistant to BD. This study indicates that TNF-α (−308G/A) and IL-10 (−1082G/A, −819C/T, and −592C/A) polymorphisms are associated with risk of BD susceptibility in Saudi patients. However, larger scale studies in Saudi population as well as in other ethnicities are needed to confirm this association. PMID:26451120

  7. 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

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

    PubMed Central

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

    2010-01-01

    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. Electronic supplementary material The online version of this article (doi:10.1007/s00122-010-1395-5) contains supplementary material, which is available to authorized users. PMID:20589365

  9. 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

  10. 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.

  11. Screening of clock gene polymorphisms demonstrates association of a PER3 polymorphism with morningness-eveningness preference and circadian rhythm sleep disorder.

    PubMed

    Hida, Akiko; Kitamura, Shingo; Katayose, Yasuko; Kato, Mie; Ono, Hiroko; Kadotani, Hiroshi; Uchiyama, Makoto; Ebisawa, Takashi; Inoue, Yuichi; Kamei, Yuichi; Okawa, Masako; Takahashi, Kiyohisa; Mishima, Kazuo

    2014-09-09

    A system of self-sustained biological clocks controls the 24-h rhythms of behavioral and physiological processes such as the sleep-wake cycle. The circadian clock system is regulated by transcriptional and translational negative feedback loops of multiple clock genes. Polymorphisms in circadian clock genes have been associated with morningness-eveningness (diurnal) preference, familial advanced sleep phase type (ASPT), and delayed sleep phase type (DSPT). We genotyped single-nucleotide polymorphisms in circadian clock genes in 182 DSPT individuals, 67 free-running type (FRT) individuals, and 925 controls. The clock gene polymorphisms were tested for associations with diurnal preference and circadian rhythm sleep disorder (CRSD) phenotypes. The PER3 polymorphism (rs228697) was significantly associated with diurnal preference and the FRT phenotype. The minor allele of rs228697 was more prevalent in evening types than in morning types (sex-adjusted odds ratio (OR), 2.483, Bonferroni-corrected P = 0.012) and in FRT individuals compared with the controls (age- and sex-adjusted OR, 2.021, permutated P = 0.017). Our findings support the notion that PER3 polymorphisms could be a potential genetic marker for an individual's circadian and sleep phenotypes.

  12. Association between RsaI polymorphism in estrogen receptor β gene and male infertility.

    PubMed

    Bordin, B M; Moura, K K V O

    2015-09-21

    The estrogen receptor β (ERβ) gene plays an important role in the regulation of fertility in both males and females. The RsaI polymorphism in ERβ is associated with male infertility in Caucasian patients. The aim of this study was to investigate the frequency of this polymorphism in the etiology of idiopathic male infertility and its correlation with smoking habits. We analyzed 287 Brazilian men, including 161 infertile and 126 fertile men, to evaluate the association between the RsaI polymorphism and male infertility. The RsaI variant alleles of all patients were determined by allele-specific polymerase chain reaction. Compared with a control group (normozoospermic men), the frequency of the RsaI AG-genotype was four times higher in infertile men (P = 0.01), five times higher in azoospermic men (P = 0.02), and seven times higher in teratozoospermic men (P = 0.001). The frequency of the RsaI AG-genotype was three times higher in infertile smokers (P = 0.038) compared with infertile nonsmokers, and nine times higher in azoospermic smokers (P = 0.035) compared with azoospermic nonsmokers. The RsaI polymorphism in ERβ may have modulating effects on human spermatogenesis. There seems to be a consistent association between RsaI polymorphism and smoking habits in infertile men.

  13. 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

  14. 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

    2016-01-04

    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.

  15. 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

  16. Genetic effects of common polymorphisms in estrogen receptor alpha gene on osteoarthritis: a meta-analysis

    PubMed Central

    Ma, Hecheng; Wu, Weiqian; Yang, Xiaodi; Liu, Jianguo; Gong, Yubao

    2015-01-01

    Objective: The estrogen receptor alpha (ESR1) gene has been implicated in the etiology of osteoarthritis (OA). However, the results are conflicting. We assessed the association of three common ESR1 polymorphisms, rs2234693, rs9340799 and rs2228480, with OA in this meta-analysis. Methods: A comprehensive search was performed to identify related studies. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed or random effects model. Results: 15 studies (7036 cases and 9669 controls) for rs2234693 polymorphism, 14 studies (3904 cases and 6991 controls) for rs9340799 and 3 studies (331 cases and 619 controls) for rs2228480 polymorphism were identified. The final results indicated that the G allele in ESR1 rs9340799 was associated with decreased OA risk (GG+GA vs. AA: OR=0.878, 95% CI=0.792-0.972, P=0.012; G vs. A: OR=0.902, 95% CI=0.836-0.975, P=0.009). The A allele in rs2228480 might be associated with increased OA risk. But no significant association of rs2234693 polymorphism with OA susceptibility was observed. Conclusions: This meta-analysis indicates rs9340799 and rs2228480 rather than rs2234693 polymorphisms are associated with the incidence of OA. Some stable associations should be further confirmed in future. PMID:26550281

  17. Association of severe micropenis with Gly146Ala polymorphism in the gene for steroidogenic factor-1.

    PubMed

    Wada, Yuka; Okada, Michiyo; Hasegawa, Tomonobu; Ogata, Tsutomu

    2005-08-01

    Steroidogenic factor-1 (SF-1) regulates the transcription of multiple genes involved in the androgen biosynthesis, and SF-1 Gly146Ala polymorphism is known to reduce the transactivation function by approximately 20%. To examine whether the Gly146Ala polymorphism constitutes a susceptibility factor for the development of micropenis (MP), we analyzed this polymorphism in a total of 52 patients with micropenis (T-MP) consisting of 30 patients with severe MP below -2.5 SD (S-MP) and 22 patients with mild MP from -2.1 SD to -2.5 SD (M-MP), together with 115 control males. The Ala allele, the Ala/Gly genotype, and the Ala/Ala plus Ala/Gly genotype frequencies were significantly higher in the S-MP patients than in the control males, whereas the allele and the genotype frequencies were comparable between the M-MP patients and the control males. The results suggest that the SF-1 Gly146Ala polymorphism may constitute a susceptibility factor for the development of S-MP, and that M-MP can be regarded as a normal variation in terms of the polymorphism effect.

  18. Technologies for individual genotyping: detection of genetic polymorphisms in drug targets and disease genes.

    PubMed

    Shi, Michael M

    2002-01-01

    Genetic variations have been associated with a predisposition to common diseases and individual variations in drug responses. Identification and genotyping a vast number of genetic polymorphisms in large populations are increasingly important for disease gene identification and pharmacogenetics. Commonly used gel electrophoresis-based genotyping methods for known polymorphisms include polymerase chain reaction (PCR) coupled with restriction fragment-length polymorphism analysis, allele-specific amplification, and oligonucleotide ligation assay. Fluorescent dye-based DNA fragmentation has been extensively used for high-throughput microsatellite or short tandem-repeat genotyping. TaqMan and molecular beacon genotyping are commonly used homogeneous solution hybridization technologies. Because of the ease of experimental assay design, single nucleotide polymorphism (SNP) genotyping methods based on single-base extension are in rapid development, such as fluorescence homogenous assays, pyrosequencing and mass spectrometry. Non-PCR based genotyping assays such as Invader trade mark assays are promised to genotype directly from genomic DNA without the requirement of PCR amplification. The DNA microarray is a solid phase genotyping format that is rapidly developing for parallel genotyping of a large number of SNPs simultaneously. Advanced technologies to identify genetic polymorphisms rapidly, accurately, and cost effectively will fundamentally change the practice of medicine by allowing physicians to prescribe medicine based on a patient's genetic make-up.

  19. 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

  20. Angiotensin-converting enzyme gene (ACE) insertion/deletion polymorphism in Mexican populations.

    PubMed

    Vargas-Alarcón, Gilberto; Hernández-Pacheco, Guadalupe; Rodríguez-Pérez, José Manuel; Pérez-Hernández, Nonanzit; Pavón, Zinnia; Fragoso, José Manuel; Juarez-Cedillo, Teresa; Villarreal-Garza, Cynthia; Granados, Julio

    2003-12-01

    The angiotensin-converting enzyme gene (ACE) insertion/deletion polymorphism was determined in 211 Mexican healthy individuals belonging to different Mexican ethnic groups (98 Mestizos, 64 Teenek, and 49 Nahuas). ACE polymorphism differed among Mexicans with a high frequency of the D allele and the D/D genotype in Mexican Mestizos. The D/D genotype was absent in Teenek and present in only one Nahua individual (2.0%). When comparisons were made, we observed that Caucasian, African, and Asian populations presented the highest frequencies of the D allele, whereas Amerindian (Teenek and Pima) and Australian Aboriginals showed the highest frequencies of the I allele. The distribution of I/D genotype was heterogeneous in all populations: Australian Aboriginals presented the lowest frequency (4.9%), whereas Nahuas presented the highest (73.4%). The present study shows the frequencies of a polymorphism not analyzed previously in Mexican populations and establishes that this polymorphism distinguishes the Amerindian populations of other groups. On the other hand, since ACE alleles have been associated with genetic susceptibility to developing cardiovascular diseases and hypertension, knowledge of the distribution of these alleles could help to define the true significance of ACE polymorphism as a genetic susceptibility marker in the Amerindian populations.

  1. Association between Estrogen Receptor Gene Polymorphisms and Depression in Post-Menopausal Women: A Preliminary Study

    PubMed Central

    Pae, Chi Un; Kim, Mi Ran; Min, Jung Ah; Kim, Kyung Hee; Lee, Chang Uk; Lee, Chul; Paik, In Ho

    2010-01-01

    Post-menopausal women experience variable biological and psychological changes. The effect of reduced levels of estrogen can effect on post-menopausal depression. Estrogen triggers physiological responses by binding to the estrogen receptor (ER). Two subtypes of ER, ERa and ERb are now known. We investigated the significance of ERa and ERb polymorphisms and post-menopasal depression in this study. Forty three women with post-menopausal depression and 63 post-menopausal women without depression as normal controls were recruited. Polymerase chain reaction-restriction fragment length polymorphism method was used to investigate genotypes of ERa and ERb polymorphisms. Genotypes of PvuII and XbaI polymorphism of ERa receptor were significantly different in patients with post-menopausal depression comparing with controls. Genotypes of ERb did not show association with post-menopausal depression. Our study showed that ERa receptor polymorphism had an association with depression in post-menopausal women. It suggests that investigation of ER genes and their functions might be important for understanding pathophysilogical mechanism of post-menopausal depression. PMID:20927313

  2. Polymorphisms in candidate genes for type 2 diabetes mellitus in a Mexican population with metabolic syndrome findings.

    PubMed

    Sánchez-Corona, J; Flores-Martínez, S E; Machorro-Lazo, M V; Galaviz-Hernández, C; Morán-Moguel, M C; Perea, F J; Mújica-López, K I; Vargas-Ancona, L; Laviada-Molina, H A; Fernández, V; Pardío, J; Arroyo, P; Barrera, H; Hanson, R L

    2004-01-01

    The metabolic or insulin resistance syndrome, characterized by hypertension, dyslipidemia, glucose intolerance and hyperinsulinemia, may have genetic determinants. The insulin gene (INS), insulin receptor gene (INSR) and insulin receptor substrate 1 gene (IRS1) have been proposed as candidate genes. We examined eight polymorphisms in these genes in 163 individuals from Yucatan, Mexico; this population has a high prevalence of obesity, type 2 diabetes mellitus and dyslipidemia. Subjects were evaluated for body mass index (BMI) and blood pressure. Blood samples were collected to determine glucose, insulin, triglycerides and cholesterol levels, as well as for DNA isolation. Restriction fragment length polymorphisms in INS, INSR and IRS1 were identified by polymerase chain reaction and digestion with selected restriction enzymes. Among the eight polymorphisms analyzed, the PstI polymorphism in INS was significantly associated with hypertriglyceridemia and with the presence of at least one abnormality related to the metabolic syndrome (P=0.007 and 0.004, respectively). The MaeIII polymorphism in INS was associated with fasting hyperinsulinemia (P=0.045). In multilocus analyses including both INS polymorphisms, significant associations were seen with hypertriglyceridemia (P=0.006), hypercholesterolemia (P=0.031) and with presence of at least one metabolic abnormality (P=0.009). None of the polymorphisms in INSR or IRS1 was associated with any of these traits. These findings suggest that the insulin gene may be an important determinant of metabolic syndrome, and particularly of dyslipidemia, in this population.

  3. Structure and polymorphism of the mouse prion protein gene.

    PubMed Central

    Westaway, D; Cooper, C; Turner, S; Da Costa, M; Carlson, G A; Prusiner, S B

    1994-01-01

    Missense mutations in the prion protein (PrP) gene, overexpression of the cellular isoform of PrP (PrPC), and infection with prions containing the scrapie isoform of PrP (PrPSc) all cause neurodegenerative disease. To understand better the physiology and expression of PrPC, we retrieved mouse PrP gene (Prn-p) yeast artificial chromosome (YAC), cosmid, phage, and cDNA clones. Physical mapping positions Prn-p approximately 300 kb from ecotropic virus integration site number 4 (Evi-4), compatible with failure to detect recombination between Prn-p and Evi-4 in genetic crosses. The Prn-pa allele encompasses three exons, with exons 1 and 2 encoding the mRNA 5' untranslated region. Exon 2 has no equivalent in the Syrian hamster and human PrP genes. The Prn-pb gene shares this intron/exon structure but harbors an approximately 6-kb deletion within intron 2. While the Prn-pb open reading frame encodes two amino acid substitutions linked to prolonged scrapie incubation periods, a deletion of intron 2 sequences also characterizes inbred strains such as RIII/S and MOLF/Ei with shorter incubation periods, making a relationship between intron 2 size and scrapie pathogenesis unlikely. The promoter regions of a and b Prn-p alleles include consensus Sp1 and AP-1 sites, as well as other conserved motifs which may represent binding sites for as yet unidentified transcription factors. Images PMID:7912827

  4. Functional expression of the globular domain of human adiponectin in Pichia pastoris.

    PubMed

    Liu, De-Guo; Liu, Hong-Lei; Song, Tan-Jing; Huang, Hai-Yan; Li, Xi; Tang, Qi-Qun

    2007-11-23

    Adiponectin is an adipokine that predominantly synthesized and secreted from adipocytes mainly in the white adipose tissue. Here, we report that we have successfully expressed human gAdiponectin (the globular domain of adiponectin) in the methylotrophic yeast Pichia pastoris after codon optimization and established the purification procedure. The human gAdiponectin gene was designed and synthesized by PCR according to the P. pastoris preferred codons, and then inserted into the P. pastoris pPIC9K expression vector. The plasmid was electroporated into the P. pastoris strain GS115 and only the G418 resistance colonies could produce the gAdiponectin. After fermentation and purification, we could get 1.2g of recombinant gAdiponectin (purity is approximately 95%) from a 24 L culture media. The recombinant gAdiponectin is fully functional as evidenced by induction the phosphorylation of ACC in differentiated C2C12 myotubes, significantly lowering the blood glucose level and accelerating the clearance of free fatty acid in animal models.

  5. Nicotinic Acid Increases Adiponectin Secretion from Differentiated Bovine Preadipocytes through G-Protein Coupled Receptor Signaling

    PubMed Central

    Kopp, Christina; Hosseini, Afshin; Singh, Shiva P.; Regenhard, Petra; Khalilvandi-Behroozyar, Hamed; Sauerwein, Helga; Mielenz, Manfred

    2014-01-01

    The transition period in dairy cows (3 weeks prepartum until 3 weeks postpartum) is associated with substantial mobilization of energy stores, which is often associated with metabolic diseases. Nicotinic acid (NA) is an antilipolytic and lipid-lowering compound used to treat dyslipidaemia in humans, and it also reduces non-esterified fatty acids in cattle. In mice the G-protein coupled receptor 109A (GPR109A) ligand NA positively affects the secretion of adiponectin, an important modulator of glucose and fat metabolism. In cattle, the corresponding data linking NA to adiponectin are missing. Our objective was to examine the effects of NA on adiponectin and AMPK protein abundance and the expression of mRNAs of related genes such as chemerin, an adipokine that enhances adiponectin secretion in vitro. Differentiated bovine adipocytes were incubated with pertussis toxin (PTX) to verify the involvement of GPR signaling, and treated with 10 or 15 µM NA for 12 or 24 h. NA increased adiponectin concentrations (p ≤ 0.001) and the mRNA abundances of GPR109A (p ≤ 0.05) and chemerin (p ≤ 0.01). Pre-incubation with PTX reduced the adiponectin response to NA (p ≤ 0.001). The NA-stimulated secretion of adiponectin and the mRNA expression of chemerin in the bovine adipocytes were suggestive of GPR signaling-dependent improved insulin sensitivity and/or adipocyte metabolism in dairy cows. PMID:25411802

  6. Relationships of growth hormone gene and milk protein polymorphisms to milk production traits in Simmental cattle.

    PubMed

    Falaki, M; Prandi, A; Corradini, C; Sneyers, M; Gengler, N; Massart, S; Fazzini, U; Burny, A; Portetelle, D; Renaville, R

    1997-02-01

    The importance of milk proteins and the positive effect of administration of growth hormone (GH) on milk production, and the presence in some dairy cattle lines of greater GH concentrations prompted us to examine the presence of restriction fragment length polymorphism at the GH gene using the restriction enzyme TaqI and to investigate associations between this polymorphism in Simmental cows and bulls, as well as milk protein variants in Simmental cows, and milk production traits. Blood and milk were sampled from 279 Italian Simmental cows and semen was collected from 148 bulls of the same breed. Two fragment bands, denoted A and B, of 6200 and 5200 bp respectively, were examined and three patterns, AA, AB and BB, were found in both animal samples. All variants previously reported in other studies, for kappa, beta, and alpha s1-caseins, and beta-lactoglobulin, were found in the cows' samples. For the cows' samples, a BLUP (Best Linear Unbiased Predictor) analysis of results was performed using a REML (Restricted Maximum Likelihood) program and known heritabilities, whereas for bulls we have performed a General Linear Model analysis. The effect of GH gene polymorphism, using TaqI restriction enzyme, on milk production traits was not significant, but bulls of BB pattern had a higher breeding value for milk yield than AA bulls (P < 0.05). For the kappa-casein genotypic effects, cows of AB genotype gave milk with 1.53 +/- 0.70 g/kg less fat than cows of AA genotype. In addition, breeding values for milk protein content were significantly higher in BB bulls, with 0.87 +/- 0.32 and 0.71 +/- 0.34 g/kg more milk protein than AA and AB bulls respectively. Thus, our results revealed a GH gene polymorphism and indicated significant effects of milk protein polymorphisms on milk production traits in the Italian Simmental breed.

  7. Association between Osteopontin Promoter Gene Polymorphisms and Haplotypes with Risk of Diabetic Nephropathy

    PubMed Central

    Cheema, Balneek Singh; Iyengar, Sreenivasa; Sharma, Rajni; Kohli, Harbir Singh; Bhansali, Anil; Khullar, Madhu

    2015-01-01

    Background: Osteopontin (OPN) C-443T promoter polymorphism has been shown as a genetic risk factor for diabetic nephropathy (DN) in type 2 diabetic patients (T2D). Methods: In the present study we investigated the association of three functional promoter gene polymorphisms C-443T, delG-156G, and G-66T and their haplotypes with the risk of DN and estimated Glomerular Filtration Rate (eGFR) in Asian Indians T2D patients using Real time PCR based Taqman assay. A total of 1165 T2D patients, belonging to two independently ascertained Indian Asian cohorts, were genotyped for three OPN promoter polymorphisms C-443T (rs11730582), delG-156G (rs17524488) and G-66T (rs28357094). Results: -156G allele and GG genotypes (delG-156G) and haplotypes G-C-G and T-C-G (G-66T, C-443T, delG-156G) were associated with decreased risk of DN and higher eGFR. Haplotype G-T-delG and T-T-delG (G-66T, C-443T, delG-156G) were identified as risk haplotypes, as shown by lower eGFR. Conclusion: This is the first study to report an association of OPN promoter gene polymorphisms; G-66T and delG-156G and their haplotypes with DN in T2D. Our results suggest an association between OPN promoter gene polymorphisms and their haplotypes with DN. PMID:26239559

  8. Association between interluekin-17 gene polymorphisms and the risk of cervical cancer in a Chinese population

    PubMed Central

    Cong, Jianglin; Liu, Riming; Wang, Xuan; Sheng, Li; Jiang, Haiyang; Wang, Weihua; Zhang, Youzhong; Yang, Shujuan; Li, Chaoying

    2015-01-01

    We conducted a study to analyze the association of three common SNPs of IL-17A rs2275913 and rs3748067 and IL-17F rs763780 gene polymorphisms with the risk of cervical cancer in a Chinese population. Our study included 352 cervical cancer patients and 352 controls between January 2013 and December 2014. Genotyping of IL-17A rs2275913 and rs3748067 and IL-17F rs763780 genes was performed by multiplex PCR assays using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). By χ2 test, there was significantly difference in the genotype distribution of IL-17A rs2275913 between cervical cancer patients and control subjects (χ2=11.45, P=0.003). By conditional logistic regression analysis, we found that individuals with the GA and AA genotypes were associated with an increased risk of cervical cancer when compared with the GG genotype in codominant model, and the adjusted Ors (95% CI) were 1.57 (1.13-2.18) and 2.01 (1.15-3.49), respectively. In dominant model, we found that the GA+AA genotype of rs2275913 was correlated with a moderate increased risk of cervical cancer compared with the GG genotype (OR=1.64, 95% CI=1.20-2.24). We only found significant interaction between rs2275913 polymorphism and HPV-16 or 18 infection in the risk of cervical cancer (P for interaction <0.05). In conclusion, our study suggests that IL-17A rs2275913 polymorphism may affect the development of cervical cancer in codominant and dominant models, and this gene polymorphism has interaction with HPV-16 or 18 infection. PMID:26464720

  9. 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

  10. 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

  11. Association of the DIO2 gene single nucleotide polymorphisms with recurrent depressive disorder.

    PubMed

    Gałecka, Elżbieta; Talarowska, Monika; Orzechowska, Agata; Górski, Paweł; Bieńkiewicz, Małgorzata; Szemraj, Janusz

    2015-01-01

    Genetic factors may play a role in the etiology of depressive disorder. The type 2 iodothyronine deiodinase gene (DIO2) encoding the enzyme catalyzing the conversion of T4 to T3 is suggested to play a role in the recurrent depressive disorder (rDD). The current study investigates whether a specific single nucleotide polymorphism (SNP) of the DIO2 gene, Thr92Ala (T/C); rs 225014 or ORFa-Gly3Asp (C/T); rs 12885300, correlate with the risk for recurrent depression. Genotypes for these two single nucleotide polymorphisms (SNPs) were determined in 179 patients meeting the ICD-10 criteria for rDD group and in 152 healthy individuals (control group) using a polymerase chain reaction (PCR) based method. The specific variant of the DIO2 gene, namely the CC genotype of the Thr92Ala polymorphism, was more frequently found in healthy subjects than in patients with depression, what suggests that it could potentially serve as a marker of a lower risk for recurrent depressive disorder. The distribution of four haplotypes was also significantly different between the two study groups with the TC (Thr-Gly) haplotype more frequently detected in patients with depression. In conclusion, data generated from this study suggest for the first time that DIO2 gene may play a role in the etiology of the disease, and thus should be further investigated. PMID:26098717

  12. A study on the relationship between TCTA tetranucleotide polymorphism of the HPRT gene and primary hyperuricemia.

    PubMed

    Zhu, Y S; Wei, S G; Sun, R F; Feng, J L; Kuang, W J; Lai, J H; Li, S B

    2011-12-15

    We examined polymorphism of the TCTA tetranucleotide sequence in the 3rd intron of the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene in the Han population of Ningxia Province in China. We also looked for a possible relationship between STR polymorphism in the 3rd intron of the HPRT gene and primary hyperuricemia. We used Chelex-100 to extract DNA, then PCR, PAGE and silver staining for allele genotyping and DNA sequencing to obtain the distribution of the alleles. We found, for the first time, that there is high STR polymorphism in the 3rd intron of the HPRT gene. We detected 5 STR alleles in this intron in the Han population of Ningxia Province, with 15 genotypes in females; significant differences were observed in the distribution of alleles and genotypes between control and patient groups for both males and females. Alleles of the TCTA repeat in the 3rd intron of the HPRT gene were found to be associated with primary hyperuricemia; consequently, these alleles may be considered risk factors for primary hyperuricemia.

  13. MEFV gene polymorphisms and TNFRSF1A mutation in patients with inflammatory myopathy with abundant macrophages

    PubMed Central

    Fujikawa, K; Migita, K; Shigemitsu, Y; Umeda, M; Nonaka, F; Tamai, M; Nakamura, H; Mizokami, A; Tsukada, T; Origuchi, T; Yonemitsu, N; Yasunami, M; Kawakami, A; Eguchi, K

    2014-01-01

    Inflammatory myopathy with abundant macrophages (IMAM) has recently been proposed as a new clinical condition. Although IMAM shares certain similarities with other inflammatory myopathies, the mechanisms responsible for this condition remain unknown. Patients with familial Mediterranean fever (FMF) and tumour necrosis factor receptor-associated periodic syndrome (TRAPS) also often develop myalgia. We therefore investigated the polymorphisms or mutations of MEFV and TNFRSF1A genes in patients with IMAM to identify their potential role in this condition. We analysed the clinical features of nine patients with IMAM and sequenced exons of the MEFV and TNFRSF1A genes. The patients with IMAM had clinical symptoms such as myalgia, muscle weakness, erythema, fever and arthralgia. Although none of the patients were diagnosed with FMF or TRAPS, seven demonstrated MEFV polymorphisms (G304R, R202R, E148Q, E148Q-L110P and P369S-R408Q), and one demonstrated a TNFRSF1A mutation (C43R). These results suggest that MEFV gene polymorphisms and TNFRSF1A mutation are susceptibility and modifier genes in IMAM. PMID:24965843

  14. Vitamin D and polymorphisms of VDR gene in patients with systemic lupus erythematosus.

    PubMed

    Monticielo, Odirlei André; Teixeira, Thaisa de Mattos; Chies, José Artur Bogo; Brenol, João Carlos Tavares; Xavier, Ricardo Machado

    2012-10-01

    The susceptibility for the development of systemic lupus erythematosus (SLE) is related to environmental, hormonal, genetic, and immunological factors. Numerous genes have been linked to the emergence of SLE, including vitamin D receptor (VDR) gene that synthesizes the receptor of vitamin D. Several polymorphisms have been described since the discovery of this gene, and their effects on VDR activity are still poorly understood. Vitamin D's biological functions are mediated by VDR. Vitamin D exerts many actions on the immune system, and several studies have suggested its role in the pathogenesis of autoimmune diseases. SLE patients have low blood levels of vitamin D, which raises the possibility of association between the deficiency of this vitamin and the onset of the disease. BsmI and FokI polymorphic variants seem to be related to the onset of the disease in Asian patients. In this article, we review the aspects related to the metabolism and immunoregulatory effects of vitamin D, VDR, and main polymorphisms involving the VDR gene and the relationship between vitamin D levels and its receptor with SLE.

  15. Polymorphisms in the ghrelin gene and their associations with milk yield and quality in water buffaloes.

    PubMed

    Gil, F M M; de Camargo, G M F; Pablos de Souza, F R; Cardoso, D F; Fonseca, P D S; Zetouni, L; Braz, C U; Aspilcueta-Borquis, R R; Tonhati, H

    2013-05-01

    Ghrelin is a gastrointestinal hormone that acts in releasing growth hormone and influences the body general metabolism. It has been proposed as a candidate gene for traits such as growth, carcass quality, and milk production of livestock because it influences feed intake. In this context, the aim of this study was to verify the existence of polymorphisms in the ghrelin gene and their associations with milk, fat and protein yield, and percentage in water buffaloes (Bubalus bubalis). A group of 240 animals was studied. Five primer pairs were used and 11 single nucleotide polymorphisms (SNP) were found in the ghrelin gene by sequencing. The animals were genotyped for 8 SNP by PCR-RFLP. The SNP g.960G>A and g.778C>T were associated with fat yield and the SNP g.905T>C was associated with fat yield and percentage and protein percentage. These SNP are located in intronic regions of DNA and may be in noncoding RNA sites or affect transcriptional efciency. The ghrelin gene in buffaloes influences milk fat and protein synthesis. The polymorphisms observed can be used as molecular markers to assist selection. PMID:23497998

  16. Genetic diversity and prevalence of CCR2-CCR5 gene polymorphisms in the Omani population

    PubMed Central

    Al-Mahruqi, Samira H.; Zadjali, Fahad; Beja-Pereira, Albano; Koh, Crystal Y.; Balkhair, Abdullah; Al-Jabri, Ali A.

    2014-01-01

    Polymorphisms in the regulatory region of the CCR5 gene affect protein expression and modulate the progress of HIV-1 disease. Because of this prominent role, variations in this gene have been under differential pressure and their frequencies vary among human populations. The CCR2V64I mutation is tightly linked to certain polymorphisms in the CCR5 gene. The current Omani population is genetically diverse, a reflection of their history as traders who ruled extensive regions around the Indian Ocean. In this study, we examined the CCR2-CCR5 haplotypes in Omanis and compared the patterns of genetic diversity with those of other populations. Blood samples were collected from 115 Omani adults and genomic DNA was screened to identify the polymorphic sites in the CCR5 gene and the CCR2V64I mutation. Four minor alleles were common: CCR5-2554T and CCR5-2086G showed frequencies of 49% and 46%, respectively, whereas CCR5-2459A and CCR5-2135C both had a frequency of 36%. These alleles showed moderate levels of heterozygosity, indicating that they were under balancing selection. However, the well-known allele CCR5Δ32 was relatively rare. Eleven haplotypes were identified, four of which were common: HHC (46%), HHE (20%), HHA (14%) and HHF*2 (12%). PMID:24688285

  17. 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.

  18. 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

    2009-02-03

    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.

  19. Polymorphisms in the ghrelin gene and their associations with milk yield and quality in water buffaloes.

    PubMed

    Gil, F M M; de Camargo, G M F; Pablos de Souza, F R; Cardoso, D F; Fonseca, P D S; Zetouni, L; Braz, C U; Aspilcueta-Borquis, R R; Tonhati, H

    2013-05-01

    Ghrelin is a gastrointestinal hormone that acts in releasing growth hormone and influences the body general metabolism. It has been proposed as a candidate gene for traits such as growth, carcass quality, and milk production of livestock because it influences feed intake. In this context, the aim of this study was to verify the existence of polymorphisms in the ghrelin gene and their associations with milk, fat and protein yield, and percentage in water buffaloes (Bubalus bubalis). A group of 240 animals was studied. Five primer pairs were used and 11 single nucleotide polymorphisms (SNP) were found in the ghrelin gene by sequencing. The animals were genotyped for 8 SNP by PCR-RFLP. The SNP g.960G>A and g.778C>T were associated with fat yield and the SNP g.905T>C was associated with fat yield and percentage and protein percentage. These SNP are located in intronic regions of DNA and may be in noncoding RNA sites or affect transcriptional efciency. The ghrelin gene in buffaloes influences milk fat and protein synthesis. The polymorphisms observed can be used as molecular markers to assist selection.

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. PPARα gene variants as predicted performance-enhancing polymorphisms in professional Italian soccer players

    PubMed Central

    Proia, Patrizia; Bianco, Antonino; Schiera, Gabriella; Saladino, Patrizia; Contrò, Valentina; Caramazza, Giovanni; Traina, Marcello; Grimaldi, Keith A; Palma, Antonio; Paoli, Antonio

    2014-01-01

    Background The PPARα gene encodes the peroxisome proliferator-activator receptor alpha, a central regulator of expression of other genes involved in fatty acid metabolism. The purpose of this study was to determine the prevalence of G allele of the PPARα intron 7 G/C polymorphism (rs4253778) in professional Italian soccer players. Methods Sixty professional soccer players and 30 sedentary volunteers were enrolled in the study. Samples of venous blood were obtained at rest, in the morning, by conventional clinical procedures; blood serum was collected and total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured. An aliquot of anticoagulant-treated blood was used to prepare genomic DNA from whole blood. The G/C polymorphic site in PPARα intron 7 was scanned by using the PCR-RFLP (polymerase chain reaction restriction fragment length polymorphism) protocol with TaqI enzyme. Results We found variations in genotype distribution of PPARα polymorphism between professional soccer players and sedentary volunteers. Particularly, G alleles and the GG genotype were significantly more frequent in soccer players compared with healthy controls (64% versus 48%). No significant correlations were found between lipid profile and genotype background. Conclusion Previous results demonstrated an association of intron 7 G allele as well as the GG genotype in endurance athletes. Our result suggests that this is the case also in professional soccer players. PMID:25525399

  6. Renin-Angiotensin System Genes Polymorphisms and Essential Hypertension in Burkina Faso, West Africa

    PubMed Central

    Tchelougou, Daméhan; Kologo, Jonas K.; Karou, Simplice D.; Yaméogo, Valentin N.; Bisseye, Cyrille; Djigma, Florencia W.; Ouermi, Djeneba; Compaoré, Tegwindé R.; Assih, Maléki; Pietra, Virginio; Zabsonré, Patrice; Simpore, Jacques

    2015-01-01

    Objective. This study aimed to investigate the association between three polymorphisms of renin-angiotensin system and the essential hypertension in the population of Burkina Faso. Methodology. This was a case-control study including 202 cases and 204 matched controls subjects. The polymorphisms were identified by a classical and a real-time PCR. Results. The AGT 235M/T and AT1R 1166A/C polymorphisms were not associated with the hypertension while the genotype frequencies of the ACE I/D polymorphism between patients and controls (DD: 66.83% and 35.78%, ID: 28.22% and 50.98%, II: 4.95% and 13.24%, resp.) were significantly different (p < 10−4). The genotype DD of ACE gene (OR = 3.40, p < 0.0001), the increasing age (OR = 3.83, p < 0.0001), obesity (OR = 4.84, p < 0.0001), dyslipidemia (OR = 3.43, p = 0.021), and alcohol intake (OR = 2.76, p < 0.0001) were identified as the independent risk factors for hypertension by multinomial logistic regression. Conclusion. The DD genotype of the ACE gene is involved in susceptibility to hypertension. Further investigations are needed to better monitor and provide individualized care for hypertensive patients. PMID:26351579

  7. 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

  8. Methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in chronic myeloid leukemia: an Egyptian study.

    PubMed

    Khorshied, Mervat Mamdooh; Shaheen, Iman Abdel Mohsen; Abu Khalil, Reham E; Sheir, Rania Elsayed

    2014-01-01

    Methylenetetrahydrofolate reductase (MTHFR) gene plays a pivotal role in folate metabolism. Several genetic variations in MTHFR gene as MTHFR-C677T and MTHFR-A1298C result in decreased MTHFR activity, which could influence efficient DNA methylation and explain susceptibility to different cancers. The etiology of chronic myeloid leukemia (CML) is obscure and little is known about individual's susceptibility to CML. In order to assess the influence of these genetic polymorphisms on the susceptibility to CML and its effect on the course of the disease among Egyptians, we performed an age-gender-ethnic matched case-control study. The study included 97 CML patients and 130 healthy controls. Genotyping of MTHFR-C677T and -A1298C was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The results showed no statistical difference in the distribution of MTHFR-C677T and -A1298C polymorphic genotypes between CML patients and controls. The frequency of MTHFR 677-TT homozygous variant was significantly higher in patients with accelerated/blastic transformation phase when compared to those in the chronic phase of the disease. In conclusion, our study revealed that MTHFR-C677T and -A1298C polymorphisms could not be considered as genetic risk factors for CML in Egyptians. However, MTHFR 677-TT homozygous variant might be considered as a molecular predictor for disease progression.

  9. Association of single nucleotide polymorphisms in cell cycle regulatory genes with oral cancer susceptibility.

    PubMed

    Murali, Abitha; Nalinakumari, K R; Thomas, Shaji; Kannan, S

    2014-09-01

    Alterations in the regulation of the cell cycle are strongly linked to tumorigenesis, so genetic variants in genes critical to control of the cycle are good candidates to have their association with susceptibility to oral cancer assessed. In this hospital-based, case-control study of 445 patients who had been newly-diagnosed with oral cancer and 449 unaffected controls, we used a multigenic approach to examine the associations among a panel of 10 selected polymorphisms in the pathway of the cell cycle that were possibly susceptible to oral cancer. Six of 9 single nucleotide polymorphisms in the cell cycle showed significant risks for oral cancer, the highest risk being evident for p27 (rs34329; Odds ratio 3.05, 95% CI 2.12 to 4.40). A significant risk of oral cancer was also evident for individual polymorphisms of cyclin E (rs1406), cyclin H (rs3093816), cyclin D1-1 (rs647451), cyclin D2 (rs3217901) and Rb1-2 (rs3092904). The risk of oral cancer increased significantly as the number of unfavourable genotypes in the pathway increased, and so the results point to a stronger combined effect of polymorphisms in important cell cycle regulatory genes on predisposition to oral cancer. PMID:24947332

  10. 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

  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. Interleukin-6 gene promoter polymorphisms and cardiovascular risk factors. A family study.

    PubMed

    Guzmán-Guzmán, Iris Paola; Muñoz-Valle, José Francisco; Flores-Alfaro, Eugenia; Salgado-Goytia, Lorenzo; Salgado-Bernabé, Aralia Berenice; Parra-Rojas, Isela

    2010-01-01

    Interleukin-6 (IL-6) is a cytokine involved in inflammatory process, as well as in glucose and lipid metabolism. Several studies of the biological relevance of IL-6 gene polymorphisms have indicated a relationship with cardiovascular disease. The aim of this study was to assess whether the -174 G/C and -572 G/C of IL-6 gene polymorphisms are associated with cardiovascular risk factors in Mexican families. Ninety members of 30 Mexican families, in which an index case (proband) had obesity, were included in the study. We evaluated the body composition by bioelectrical impedance. Peripheral blood samples were collected to determine biochemical and hematological parameters. High sensitivity C- reactive protein levels were measurement for nephelometric analysis. Screening for both polymorphisms studied was performed by PCR-RFLP. In the parents, both polymorphisms were in Hardy-Weinberg's equilibrium. The genotypes -174 GC/CC were associated with T2D (OR=1.23, IC(95%) 1.01-1.5) and highest levels of hsCRP (p=0.02), whereas genotype -572 GG was associated with T2D (OR=1.24, IC(95%) 1.04-1.47) with an inflammatory state determined by the increase in the leukocyte count (OR=1.24, IC(95%) 1.02-1.51). The genotypes -174 GC/CC and -572 GG may confer susceptibility for the development of subclinical inflammation and type 2 diabetes in Mexican families.

  13. Association of T174M polymorphism of angiotensinogen gene with essential hypertension: A meta-analysis.

    PubMed

    Liao, Xiaoyang; Yang, Zhiyi; Peng, Daqing; Dai, Hua; Lei, Yi; Zhao, Qian; Han, Yanbing; Wang, Weiwen

    2014-09-01

    The association between T174M polymorphism of angiotensinogen gene and essential hypertension risk remains controversial. We herein performed a meta-analysis to achieve a reliable estimation of their relationship. All the studies published up to May 2013 on the association between T174M polymorphism and essential hypertension risk were identified by searching the electronic repositories PubMed, MEDLINE and EMBASE, Springer, Elsevier Science Direct, Cochrane Library and Google Scholar. Data were extracted and pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Ultimately, nine eligible studies, including 2188 essential hypertension cases and 2459 controls, were enrolled in this meta-analysis. No significant associations were found under the overall ORs for M-allele comparison (M vs. T, pooled OR 0.92, 95% CI 0.62-1.37), MM vs. TT (pooled OR 0.86, 95% CI 0.29-2.51), TM vs. TT n (pooled OR 0.91, 95% CI 0.63-1.32), recessive model (MM vs. TT+TM, pooled OR 0.89, 95% CI 0.35-2.30), dominant model (MM+TM vs. TT, pooled OR 0.91, 95% CI 0.60-1.38) between T174M polymorphism and risk for essential hypertension. This meta-analysis suggested that the T174M polymorphism of the angiotensinogen gene might not be associated with the susceptibility of essential hypertension in Asian or European populations.

  14. 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

  15. 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...

  16. 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

  17. 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.

  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. Major histocompatibility complex class II A gene polymorphism in the striped bass

    SciTech Connect

    Hardee, J.J.; Godwin, U.; Benedetto, R.; McConnell, T.J.

    1995-02-01

    Adaptions of the polymerase chain reaction were used to isolate cDNA sequences encoding the Major histocompatibility complex (Mhc) class II A gene(s) of the striped bass (Morone saxatilis). Four complete Mhc class II A genes were cloned and sequenced from a specimen originating on the Roanoke River, North Carolina, and another three A genes from a specimen originating from the Santee-Cooper Reservoir, South Carolina, identifying a total of seven unique sequences. The sequence suggests the presence of at least two Mhc class II A loci. The extensive sequence variability observed between the seven different Mhc class II clones was concentrated in the {alpha}1 encoding domain. The encoded {alpha}2, transmembrane, and cytoplasmic regions of all seven striped bass genes correlated well with those of known vertebrate Mhc class II proteins. Overall, the striped bass sequences showed greatest similarity to the Mhc class II A genes of the zebrafish. Southern blot analysis demonstrated extensive polymorphism in the Mhc class II A genes in members of a Roanoke river-caught population of striped bass versus a lesser degree of polymorphism in an aquacultured Santee-Cooper population of striped bass. 55 refs., 5 figs., 1 tab.

  20. Major histocompatibility complex class II A gene polymorphism in the striped bass.

    PubMed

    Hardee, J J; Godwin, U; Benedetto, R; McConnell, T J

    1995-01-01

    Adaptions of the polymerase chain reaction were used to isolate cDNA sequences encoding the Major histocompatibility complex (Mhc) class II A gene(s) of the striped bass (Morone saxatilis). Four complete Mhc class II A genes were cloned and sequenced from a specimen originating in the Roanoke River, North Carolina, and another three A genes from a specimen originating from the Santee-Cooper Reservoir, South Carolina, identifying a total of seven unique sequences. The sequence suggests the presence of at least two Mhc class II A loci. The extensive sequence variability observed between the seven different Mhc class II clones was concentrated in the alpha 1 encoding domain. The encoded alpha 2, transmembrane, and cytoplasmic regions of all seven striped bass genes correlated well with those of known vertebrate Mhc class II proteins. Overall, the striped bass sequences showed greatest similarity to the Mhc class II A genes of the zebrafish. Southern blot analysis demonstrated extensive polymorphism in the Mhc class II A genes in members of a Roanoke river-caught population of striped bass versus a lesser degree of polymorphism in an aquacultured Santee-Cooper population of striped bass.

  1. Adiponectin and thiazolidinedione targets CRTC2 to regulate hepatic gluconeogenesis.

    PubMed

    Yoon, Young Sil; Ryu, Dongryeol; Lee, Min Woo; Hong, Sungpyo; Koo, Seung Hoi

    2009-08-31

    During fasting periods, hepatic glucose production is enhanced by glucagon to provide fuels for other organs. This process is mediated via cAMP-dependent induction of the CREB regulated transcriptional coactivator (CRTC) 2, a critical transcriptional activator for hepatic gluconeogenesis. We have previously shown that CRTC2 activity is regulated by AMP activated protein kinase (AMPK) family members. Here we show that adiponectin and thiazolidinedione directly regulate AMPK to modulate CRTC2 activity in hepatocytes. Adiponectin or thiazolidinedione lowered glucose production from primary hepatocytes. Treatment of both reagents reduced gluconeogenic gene expression as well as cAMP-mediated induction of CRE reporter, suggesting that these reagents directly affect CREB/CRTC2- dependent transcription. Furthermore, adiponectin or thiazolidinedione mediated repression of CRE activity is largely blunted by co-expression of phosphorylation defective mutant CRTC2, underscoring the importance of serine 171 residue of this factor. Taken together, we propose that adiponectin and thiazolidinedione promote the modulation of AMPK-dependent CRTC2 activity to influence hepatic gluconeogenesis.

  2. 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

  3. Brain Molecular Aging, Promotion of Neurological Disease and Modulation by Sirtuin5 Longevity Gene Polymorphism

    PubMed Central

    Glorioso, Christin; Oh, Sunghee; Douillard, Gaelle Guilloux; Sibille, Etienne

    2010-01-01

    Mechanisms determining characteristic age of onset for neurological diseases are largely unknown. Normal brain aging associates with robust and progressive transcriptome changes (“molecular aging”), but the intersection with disease pathways is mostly uncharacterized. Here, using cross-cohort microarray analysis of four human brain areas, we show that neurological disease pathways largely overlap with molecular aging and that subjects carrying a newly-characterized low-expressing polymorphism in a putative longevity gene (Sirtuin5; SIRT5prom2) have older brain molecular ages. Specifically, molecular aging was remarkably conserved across cohorts and brain areas, and included numerous developmental and transcription-regulator genes. Neurological disease-associated genes were highly overrepresented within age-related genes and changed almost unanimously in pro-disease directions, together suggesting an underlying genetic “program” of aging that progressively promotes disease. To begin testing this putative pathway, we developed and used an age-biosignature to assess five candidate longevity gene polymorphisms association with molecular aging rates. Most robustly, aging was accelerated in cingulate, but not amygdala, of subjects carrying a SIRT5 promoter polymorphism (+9yrs, p=0.004), in concordance with cingulate-specific decreased SIRT5 expression. This effect was driven by a set of core transcripts (+24 yrs, p=0.0004), many of which were mitochondrial, including Parkinson’s disease genes, PINK1 and DJ1/PARK7, hence suggesting that SIRT5prom2 may represent a risk factor for mitochondrial dysfunction-related diseases, including Parkinson s, through accelerated molecular aging of disease-related genes. Based on these results we speculate that a “common mechanism” may underlie age of onset across several neurological diseases. Confirming this pathway and its regulation by common genetic variants would provide new strategies for predicting, delaying, and

  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. 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.

  6. Polymorphism of BMPR1B, BMP15 and GDF9 fecundity genes in prolific Garole sheep.

    PubMed

    Polley, Shamik; De, Sachinandan; Brahma, Biswajit; Mukherjee, Ayan; Vinesh, P V; Batabyal, Subhasis; Arora, Jaspreet Singh; Pan, Subhransu; Samanta, Ashis Kumar; Datta, Tirtha Kumar; Goswami, Surender Lal

    2010-06-01

    Mutation studies in different prolific sheep breeds have shown that the transforming growth factor beta super family ligands viz. the growth differentiation factor 9 (GDF9/FecG), bone morphogenetic protein 15 (BMP15/FecX) and associated type I receptors, bone morphogenetic protein receptor (BMPR1B/FecB), are major determinant of ovulation rate and consequent increase in litter size. The Garole sheep is a highly prolific sheep breed of India. Characterization of fecundity genes in these animals could substantially improvise the breeding programme in these animals as well as other sheep breeds of the region. The present study was therefore designed with the objective of polymorphism study of fecundity genes in these prolific microsheep. A total of 11 point mutations were detected by polymerase chain reaction (PCR)-based method. A competitive technique called tetra-primer amplification refractory mutation system-PCR was adapted to type a total of ten points of two ovine fecundity genes (GDF9 and BMP15). The FecB locus of the BMPR1B gene and G1 locus of GDF9 gene were found to be polymorphic. In FecB locus, two genotypes, wild type (FecB(+)) and mutant (FecBB), were detected with allele frequencies of 0.39 and 0.61, respectively. At G1 locus, two genotypes, mutant (A) and wild types (G) were detected with allele frequencies of 0.18 and 0.82, respectively. This study reports Garole sheep as the fourth sheep breed after Belclare/Cambridge, Lacaune and Small-tailed Han sheep, where coexisting polymorphism has been found in two different fecundity genes (BMPRIB and GDF9 genes).

  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. Acute Otitis Media Severity: Association with Cytokine Gene polymorphisms and other Risk Factors

    PubMed Central

    McCormick, David P.; Grady, James J.; Diego, Alejandro; Matalon, Reuben; Revai, Krystal; Patel, Janak A.; Han, Yimei; Chonmaitree, Tasnee

    2011-01-01

    Background We have previously shown an association between polymorphisms of proinflammatory cytokine genes and susceptibility to upper respiratory tract infection and acute otitis media. It has not been known whether polymorphisms or risk factors are associated with the severity of acute otitis media. Objective To evaluate the influences of proinflammatory cytokine gene polymorphisms and other risk factors on severity of acute otitis media following upper respiratory infection. Methods In a prospective, longitudinal study, children aged 6-35 months were followed for one year for occurrences of upper respiratory tract infection and acute otitis media. Children were studied for TNFα-308, interleukin (IL)- 6-174 and IL-1 ß+3953 polymorphisms, taking into account age, gender, race, family history of otitis, tobacco smoke exposure, breast feeding, day of upper respiratory tract infection at the time of diagnosis and pneumococcal vaccine status. Symptoms and signs of acute otitis media were graded according to a validated scale. The association between acute otitis media clinical severity, polymorphic genotypes, and risk factors was analyzed using statistical models that account for multiple episodes of acute otitis media per child. Results A total of 295 episodes of acute otitis media in 128 subjects were included. More severe acute otitis media symptoms were associated with young age (P=0.01), family history of acute otitis media (P=0.002), tobacco smoke exposure (P=0.008), and early diagnosis of otitis after onset of upper respiratory tract infection (P=0.02). Among children with a bulging or perforated tympanic membrane (206 episodes, 104 subjects), those who had the IL- 1 ß+3953 polymorphism, experienced higher symptom scores (P<0.02). Conclusion This is the first report of the association between risk factors and acute otitis media severity. Risk factors such as tobacco smoke exposure and a positive family history appear to be more significantly associated with

  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. ADH2 gene polymorphisms are determinants of alcohol pharmacokinetics.

    PubMed

    Thomasson, H R; Beard, J D; Li, T K

    1995-12-01

    The class I hepatic alcohol dehydrogenases (ADHs) are primarily responsible for ethanol metabolism in humans. Genetic polymorphism at the ADH2 locus results in the inheritance of isozymes of strikingly different catalytic properties. The most common ADH2 allele, ADH2*1, encodes the low K(m) isozyme subunit beta 1. The ADH2*3 allele encodes a high-activity isozyme subunit of alcohol dehydrogenase, beta 3, identified in approximately 25% of African-Americans. The Vmax of beta 3 beta 3-ADH is 30 times greater than that of the beta 1 beta 1-ADH. Therefore, we hypothesized that the rate of ethanol metabolism, an important factor in the toxicity of ethanol, in persons with beta 3-containing ADH, either beta 3 beta 3- or beta 1 beta 3-ADH, would be faster than that of persons with only beta 1 beta 1-ADH. We tested this hypothesis with ethanol administered orally to healthy, young African-Americans. Three hundred and twenty-six African-American men and women were genotyped using polymerase chain reaction amplification of their leukocyte DNA followed by hybridization with allele-specific probes. One hundred twelve volunteers, selected by genotype, received an oral dose of ethanol designed to produce a blood ethanol concentration of 80 mg/dl (0.080 g/dl), when the blood alcohol concentration-time curve was extrapolated back to time 0. Ethanol metabolic rates (beta 60s) were determined in the 112 subjects from the slope of the pseudolinear portion of the blood ethanol concentration-time curves. The mean beta 60 of African-Americans having beta 3-containing ADH isozymes had significantly faster ethanol elimination rates than those with only beta 1 beta 1-ADH isozymes. There were no significant differences in body weight, ethanol intake in the week before testing, peak breath ethanol concentration, time to peak, or volume of distribution between the genotype groups. Within each of these groups, men had lower ethanol disappearance rates than women. These results demonstrate in

  11. 1236 C/T and 3435 C/T polymorphisms of the ABCB1 gene in Mexican breast cancer patients.

    PubMed

    Gutierrez-Rubio, S A; Quintero-Ramos, A; Durán-Cárdenas, A; Franco-Topete, R A; Castro-Cervantes, J M; Oceguera-Villanueva, A; Jiménez-Pérez, L M; Balderas-Peña, L M A; Morgan-Villela, G; Del-Toro-Arreola, A; Daneri-Navarro, A

    2015-02-13

    MDR1, which is encoded by the ABCB1 gene, is involved in multidrug resistance (hydrophobic), as well as the elimination of xenotoxic agents. The association between ABCB1 gene polymorphisms and breast cancer risk in different populations has been described previously; however, the results have been inconclusive. In this study, we examined the association between polymorphisms 3435 C/T and 1236 C/T in the ABCB1 gene and breast cancer development in Mexican women according to their menopausal status and molecular classification. Molecular subtypes as well as allele and genotype frequencies were analyzed. A total of 248 women with initial breast cancer diagnosis and 180 ethnically matched, healthy, unrelated individuals were enrolled. Polymerase chain reaction-restriction fragment length polymorphism was performed to detect polymorphisms 3435 C/T and 1236 C/T in the ABCB1 gene. Premenopausal T allele carriers of the 3435 C/T polymorphism showed a 2-fold increased risk of breast cancer with respect to the reference and postmenopausal groups, as well as triple-negative expression regarding the luminal A/B molecular subrogated subtypes. In contrast, the CT genotype of the 1236 polymorphism was a protective factor against breast cancer. We conclude that the T allele carrier of the 3435 C/T polymorphism in the ABCB1 gene in combination with an estrogen receptor-negative status may be an important risk factor for breast cancer development in premenopausal women.

  12. The aporphine alkaloid boldine induces adiponectin expression and regulation in 3T3-L1 cells.

    PubMed

    Yu, Bangning; Cook, Carla; Santanam, Nalini

    2009-10-01

    Adiponectin is an adipokine secreted by differentiated adipocytes. Clinical studies suggest a negative correlation between oxidative stress and adiponectin levels in patients with metabolic syndrome or cardiovascular disease. Natural compounds that can prevent oxidative stress mediated inhibition of adiponectin may be potentially therapeutic. Boldine, an aporphine alkaloid abundant in the medicinal plant Peumus boldus, is a powerful antioxidant. The current study demonstrates the effects of boldine on the expression of adiponectin and its regulators, CCAAT/enhancer binding protein-alpha (C/EBPalpha) and peroxisome proliferator-activated receptor (PPAR)-gamma, in 3T3-L1 cells. Differentiated 3T3-L1 adipocytes were exposed to either hydrogen peroxide (H(2)O(2)) (100 microM) or tumor necrosis factor-alpha (TNFalpha) (1 ng/mL) for 24 hours in the presence or absence of increasing concentrations of boldine (5-100 microM). Quantitative polymerase chain reaction showed that both the oxidants decreased the mRNA levels of adiponectin, PPARgamma, and C/EBPalpha to half of the control levels. Boldine, at all concentrations, counteracted the inhibitory effect of H(2)O(2) or TNFalpha and increased the expression of adiponectin and its regulators. The effect of boldine on adiponectin expression was biphasic, with the lower concentrations (5-25 microM) having a larger inductive effect compared to higher concentrations (50-100 microM). Boldine treatment alone in the absence of H(2)O(2) or TNFalpha was also able to induce adiponectin at the inductive phase of adipogenesis. Peroxisome proliferator response element-luciferase promoter transactivity analysis showed that boldine interacts with the PPAR response element and could potentially modulate PPAR responsive genes. Our results indicate that boldine is able to modulate the expression of adiponectin and its regulators in 3T3-L1 cells and has the potential to be beneficial in obesity-related cardiovascular disease. PMID:19857072

  13. The Aporphine Alkaloid Boldine Induces Adiponectin Expression and Regulation in 3T3-L1 Cells

    PubMed Central

    Yu, Bangning; Cook, Carla

    2009-01-01

    Abstract Adiponectin is an adipokine secreted by differentiated adipocytes. Clinical studies suggest a negative correlation between oxidative stress and adiponectin levels in patients with metabolic syndrome or cardiovascular disease. Natural compounds that can prevent oxidative stress mediated inhibition of adiponectin may be potentially therapeutic. Boldine, an aporphine alkaloid abundant in the medicinal plant Peumus boldus, is a powerful antioxidant. The current study demonstrates the effects of boldine on the expression of adiponectin and its regulators, CCAAT/enhancer binding protein-α (C/EBPα) and peroxisome proliferator-activated receptor (PPAR)-γ, in 3T3-L1 cells. Differentiated 3T3-L1 adipocytes were exposed to either hydrogen peroxide (H2O2) (100 μM) or tumor necrosis factor-α (TNFα) (1 ng/mL) for 24 hours in the presence or absence of increasing concentrations of boldine (5–100 μM). Quantitative polymerase chain reaction showed that both the oxidants decreased the mRNA levels of adiponectin, PPARγ, and C/EBPα to half of the control levels. Boldine, at all concentrations, counteracted the inhibitory effect of H2O2 or TNFα and increased the expression of adiponectin and its regulators. The effect of boldine on adiponectin expression was biphasic, with the lower concentrations (5–25 μM) having a larger inductive effect compared to higher concentrations (50–100 μM). Boldine treatment alone in the absence of H2O2 or TNFα was also able to induce adiponectin at the inductive phase of adipogenesis. Peroxisome proliferator response element-luciferase promoter transactivity analysis showed that boldine interacts with the PPAR response element and could potentially modulate PPAR responsive genes. Our results indicate that boldine is able to modulate the expression of adiponectin and its regulators in 3T3-L1 cells and has the potential to be beneficial in obesity-related cardiovascular disease. PMID:19857072

  14. Sex-Specific Effects of Adiponectin on Carotid Intima-Media Thickness and Incident Cardiovascular Disease

    PubMed Central

    Persson, Jonas; Strawbridge, Rona J; McLeod, Olga; Gertow, Karl; Silveira, Angela; Baldassarre, Damiano; Van Zuydam, Natalie; Shah, Sonia; Fava, Cristiano; Gustafsson, Stefan; Veglia, Fabrizio; Sennblad, Bengt; Larsson, Malin; Sabater-Lleal, Maria; Leander, Karin; Gigante, Bruna; Tabak, Adam; Kivimaki, Mika; Kauhanen, Jussi; Rauramaa, Rainer; Smit, Andries J; Mannarino, Elmo; Giral, Philippe; Humphries, Steve E; Tremoli, Elena; de Faire, Ulf; Lind, Lars; Ingelsson, Erik; Hedblad, Bo; Melander, Olle; Kumari, Meena; Hingorani, Aroon; Morris, Andrew D; Palmer, Colin N A; Lundman, Pia; Öhrvik, John; Söderberg, Stefan; Hamsten, Anders

    2015-01-01

    Background Plasma adiponectin levels have previously been inversely associated with carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis. In this study, we used a sex-stratified Mendelian randomization approach to investigate whether adiponectin has a causal protective influence on IMT. Methods and Results Baseline plasma adiponectin concentration was tested for association with baseline IMT, IMT progression over 30 months, and occurrence of cardiovascular events within 3 years in 3430 participants (women, n =1777; men, n =1653) with high cardiovascular risk but no prevalent disease. Plasma adiponectin levels were inversely associated with baseline mean bifurcation IMT after adjustment for established risk factors (β =−0.018, P<0.001) in men but not in women (β =−0.006, P =0.185; P for interaction =0.061). Adiponectin levels were inversely associated with progression of mean common carotid IMT in men (β =−0.0022, P =0.047), whereas no association was seen in women (0.0007, P =0.475; P for interaction =0.018). Moreover, we observed that adiponectin levels were inversely associated with coronary events in women (hazard ratio 0.57, 95% CI 0.37 to 0.87) but not in men (hazard ratio 0.82, 95% CI 0.54 to 1.25). A gene score of adiponectin-raising alleles in 6 loci, reported recently in a large multi-ethnic meta-analysis, was inversely associated with baseline mean bifurcation IMT in men (β =−0.0008, P =0.004) but not in women (β =−0.0003, P =0.522; P for interaction =0.007). Conclusions This report provides some evidence for adiponectin protecting against atherosclerosis, with effects being confined to men; however, compared with established cardiovascular risk factors, the effect of plasma adiponectin was modest. Further investigation involving mechanistic studies is warranted. PMID:26276317

  15. Autoinflammatory gene polymorphisms and susceptibility to UK juvenile idiopathic arthritis

    PubMed Central

    2013-01-01

    Background To investigate the autoinflammatory hereditary periodic fever syndrome genes MVK and TNFRSF1A, and the NLRP1 and IL1 genes, for association with juvenile idiopathic arthritis (JIA). Methods For MVK, TNFRSF1A and NLRP1 pair-wise tagging SNPs across each gene were selected and for IL1A SNPs from a prior meta-analysis were included. 1054 UK Caucasian JIA patients were genotyped by Sequenom iPlex MassARRAY and allele and genotype frequencies compared with 5380 unrelated healthy UK Caucasian controls. Results Four SNPs were significantly associated with UK JIA: rs2071374 within intron 4 of IL1A (ptrend=0.006), rs2228576 3’ of TNFRSF1A (ptrend=0.009) and 2 SNPs, rs11836136 and rs7957619, within MVK (ptrend=0.006, ptrend=0.005 respectively). In all cases the association appeared to be driven by the systemic-onset JIA (SoJIA) subtype. Genotype data for the two MVK SNPs was available in a validation cohort of 814 JIA (oligoarticular and RF negative polyarticular) cases and 3058 controls from the US. Replication was not confirmed, however, further suggesting that this association is specific to SoJIA. Conclusions These findings extend the observations of the relevance of studying monogenic loci as candidates for complex diseases. We provide novel evidence of association of MVK and TNFRSF1A with UK JIA, specifically driven by association with SoJIA and further confirm that the IL1A SNP association with SoJIA is subtype specific. Replication is required in independent cohorts. PMID:23547563

  16. CYP11B2 gene polymorphism among coronary heart disease patients and blood donors in Malaysia.

    PubMed

    Normaznah, Y; Azizah, M R; Kuak, S H; Rosli, M A

    2015-04-01

    Various previous studies have reported the implication of CYP11B2 gene polymorphism in the pathophysiology of cardiovascular diseases. In particular, the -344T/C polymorphism, which is located at a putative binding site for the steroidogenic transcription factor (SF-1) has been associated with essential hypertension, left ventricular dilation and coronary heart disease. In the present study, we aim to determine the allele and genotype frequencies of the CYP11B2 gene in patients with clinical manifestation of coronary heart disease and confirmed by angiography and blood donors and to calculate the association of the gene polymorphism with CHD. A total of 79 DNA from patients with coronary heart disease admitted to the National Heart Institute and 84 healthy blood donors have been genotyped using polymerase chain reaction technique followed by restriction enzyme digestion (RFLP). Results of the study demonstrated that out of 79 for the patients, 40 were homozygous T, 10 were homozygous C and 29 were heterozygous TC. The frequencies of genotype TT, CC and TC for patients were 0.5, 0.13 and 0.36 respectively. The frequencies of allele T and C in patients were 0.68 and 0.31 respectively. While for the blood donors, 40 subjects were of homozygous T, 7 were homozygous C and 37 were heterozygous TC. The genotype frequencies for the TT, CC and TC were 0.47, 0.08 and 0.44 respectively. The frequency of the allele T was 0.69 and allele C was 0.3. Chi-Square analysis showed that there was no significant difference in the genotype and C allele frequencies between the CHD patients and the blood donors. Our study suggests that there is lack of association between -344T/C polymorphism of CYP11B2 gene and coronary heart disease.

  17. 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

  18. Association of vitamin D receptor gene polymorphism with the risk of systemic lupus erythematosus.

    PubMed

    Zhou, Tian-Biao; Jiang, Zong-Pei; Lin, Zhi-Jun; Su, Ning

    2015-02-01

    Relationship between vitamin D receptor (VDR) gene polymorphism and the risk of systemic lupus erythematosus (SLE) from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR BsmI (rs1544410), Fok1 (rs2228570), ApaI (rs7975232) and TaqI (rs731236) gene polymorphism and the risk of SLE using meta-analysis method. The association studies were identified from PubMed and Cochrane Library on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Thirteen reports were recruited into this meta-analysis for the association of VDR gene polymorphism with SLE susceptibility. In this meta-analysis for overall populations, the BsmI B allele and bb genotype, Fok1 f allele and ff genotype, and ApaI aa genotype, were associated with the risk of SLE. In Asians, the BsmI B allele, BB genotype and bb genotype, Fok1 f allele and ff genotype were associated with the risk of SLE. In Africans, the BsmI B allele, BB genotype and bb genotype, Fok1 f allele and ff genotype, ApaI A allele, AA genotype and aa genotype were associated with the risk of SLE. However, VDR BsmI, Fok1, ApaI and TaqI gene polymorphism were not associated with the risk of SLE in Caucasians. In conclusion, the BsmI B allele and bb genotype, Fok1 f allele and ff genotype were associated with the risk of SLE in overall populations, and in Asians, but these associations were not found in Caucasians. However, more studies should be conducted to confirm it.

  19. 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.

  20. Polymorphisms of the thiopurine S-methyltransferase gene among the Libyan population

    PubMed Central

    Zeglam, Hamza Ben; Benhamer, Abdrazak; Aboud, Adel; Rtemi, Haitem; Mattardi, Meftah; Saleh, Saleh Suleiman; Bashein, Abdullah; Enattah, Nabil

    2015-01-01

    Background Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme that catalyses the S-methylation of 6-mercaptopurine and azathioprine. Low activity phenotypes are correlated with polymorphism in the TPMT gene. Patients with low or undetectable TMPT activity could develop severe myelosuppression when they are treated with standard doses of thiopurine drugs. Since ethnic differences in the TPMT gene polymorphism have been demonstrated worldwide, assessing it in the Libyan population is worthwhile. Methods We investigated TPMT gene polymorphism in a total of 246 Libyan healthy adult blood donors from three different Libyan regions (Tripoli, Yefren, and Tawargha) and 50 children with acute lymphoblastic leukaemia (ALL). We used polymerase chain reaction restriction length polymorphism (PCR-RFLP) and allele-specific PCR-based assays to analyse the TPMT gene for the variants *2 c.238 G>C, *3A (c.460 G>A and c.719 A>G), *3B (c.460 G>A), and *3C (c.719 A>G). Results Our results show that the TPMT variants associated with low enzymatic activity were detected in 3.25% (8 in 246) of adult Libyan individuals and the frequency of total mutant alleles was 1.63%. Heterozygous genotypes were TPMT*3A in three subjects (0.61%) and TPMT*3C in five subjects (1.02%). No TPMT*2 and TPMT*3B allelic variants and no homozygous or compound heterozygous mutant alleles were detected. The normal allele (wild-type) was found in 98.4% of the adult individuals studied. No mutant alleles were detected among the 50 children who had ALL. Conclusions We report on the presence of the TPMT*3C and *3A mutant alleles in the Libyan population. Therefore, monitoring the patients to be treated with doses of thiopurine drugs for TPMT variants is worthwhile to avoid the development of severe myelosuppression. PMID:25819542

  1. 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

  2. Association between plasminogen activator inhibitor-1 4G/5G gene polymorphism and immunoglobulin A nephropathy susceptibility.

    PubMed

    Zhou, Tian-Biao; Jiang, Zong-Pei

    2015-02-01

    The association between plasminogen activator inhibitor-1 (PAI-1) 4 G/5 G gene polymorphism and immunoglobulin A nephropathy (IgAN) risk is still controversial. A meta-analysis was performed to evaluate the association between PAI-1 4 G/5 G gene polymorphism and IgAN susceptibility. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic database. Four articles were identified for the analysis of association between PAI-1 4 G/5 G gene polymorphism and IgAN risk. 4 G allele was not associated with IgAN susceptibility in overall populations and in Asians. Furthermore, 4 G/4 G and 5 G/5 G genotype were not associated with IgAN for overall populations, Asians. In conclusion, PAI-1 4 G/5 G gene polymorphism was not associated with IgAN risk in overall populations and in Asians. However, more studies should be performed in the future.

  3. 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

  4. Association between three interleukin-10 gene polymorphisms and coronary artery disease risk: a meta-analysis

    PubMed Central

    Wang, Bing-Jian; Liu, Jie; Geng, Jin; Zhang, Qing; Hu, Ting-Ting; Xu, Biao

    2015-01-01

    Background: Previous studies have investigated the associations between interleukin-10 (IL-10) gene polymorphisms (-592C/A, -819C/T and -1082G/A) and risk of coronary artery disease (CAD). However, the results were inconsistent. The aim of this study was to clarify the relationship between IL-10 polymorphisms and CAD risk by a meta-analysis approach. Methods: The PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI) and Wanfang databases were searched according to predefined criteria for all relevant studies published before June 1, 2015. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were computed to assess the association. Results: 24 eligible studies were enrolled including 9736 CAD patients and 8606 controls. We observed a significant decreased risk of CAD for IL-10 -819C/T polymorphism (T allele vs. C allele:OR = 0.91, 95% CI = 0.84-0.99; TT vs. CT + CC:OR = 0.82, 95% CI = 0.69-0.98), especially in Asians (T allele vs. C allele:OR = 0.76, 95% CI = 0.60-0.96; TT vs. CC:OR = 0.51, 95% CI = 0.27-0.96; TT vs. CT + CC:OR = 0.62, 95% CI = 0.44-0.88). Moreover, we found IL-10 -1082G/A polymorphism might contribute to an increased CAD risk in Asians (AA vs. GG:OR = 1.89, 95% CI = 1.36-2.64; AA vs. AG + GG:OR = 1.39, 95% CI = 1.14-1.68) but not in other ethnic groups. However, no significant association between the IL-10 -592C/A polymorphism and CAD risk was observed. Conclusions: Our results indicated that IL-10 -819C/T and IL-10 -1082G/A polymorphisms significantly and race-specifically correlate with CAD risk. PMID:26770379

  5. 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.

  6. Apolipoprotein A1 gene polymorphisms as risk factors for hypertension and obesity.

    PubMed

    Chen, Elizabeth Suchi; Mazzotti, Diego Robles; Furuya, Tatiane Katsue; Cendoroglo, Maysa Seabra; Ramos, Luiz Roberto; Araujo, Lara Quirino; Burbano, Rommel Rodriguez; de Arruda Cardoso Smith, Marília

    2009-12-01

    Several polymorphisms in apolipoprotein A1 (APOA1) gene have been associated with metabolic diseases. Increased transcription efficiency was observed in -75A allele carriers compared to -75G allele homozygotes. +83C allele was associated with higher body mass index and waist-to-hip ratio in type II diabetes subjects. -75G/A and +83C/T polymorphisms were analyzed by RFLP-PCR in 334 individuals from a Brazilian elderly cohort. APOA1 polymorphisms were associated with age-related morbidities, as well as with triglycerides, total cholesterol, HDL, VLDL, LDL, creatinine, urea, albumin, glycated hemoglobin and fasting glucose serum levels. Allele frequencies were 0.102 and 0.21, respectively, for -75A and +83T. -75G allele showed significant association with hypertension (P = 0.001). An association between +83C allele and obesity was observed (P = 0.040) and this allele also showed an association with hypertension in the presence of cardiovascular disease (P = 0.047). Moreover, +83T allele was associated with lower glycated hemoglobin values (P = 0.026). To our knowledge, there is no data associating this polymorphism with glycated hemoglobin. Furthermore, individuals carrying AT haplotype have lower risk for developing hypertension (P = 0.0002), while GT haplotype carriers present decreased risk to develop obesity comparing to GC haplotype (P = 0.025). APOA1 polymorphisms analysis may be a useful tool to identify risk factors for subjects and families and clarify the physiopathological role of these polymorphisms in age-related diseases, such as hypertension and obesity.

  7. 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

  8. Apolipoprotein B Gene Polymorphisms and Dyslipidemia in HIV Infected Adult Zimbabweans

    PubMed Central

    Zhou, Danai Tavonga; Oektedalen, Olav; Duri, Kerina; Stray-Pedersen, Babill; Gomo, Exnevia

    2016-01-01

    Background: Dyslipidemia does not occur in all HIV-infected or antiretroviral therapy-experienced patients suggesting role of host genetic factors but there is paucity of data on association between dyslipidemia and gene polymorphisms in Zimbabwe. Objective: To determine association of lipoprotein levels and apolipoprotein B polymorphisms in HIV-infected adults. Method: Demographic data were collected from 103 consenting patients; lipoprotein levels were determined and blood samples were successfully genotyped for both apolipoprotein B 2488C>T Xba1 and apolipoprotein B 4154G>A p.Gln4154Lys EcoR1 polymorphisms by real time polymerase chain reaction. Results: Mean age of genotyped patients was 40.3 ± 10.1 years, 68% were female; prevalence of dyslipidemia was 67.4%. Of 103 samples genotyped for apolipoprotein B Xba1 polymorphism, 76 (74%) were homozygous C/C, 24 (23%) were heterozygous C/T and only three (3%) were homozygous T/T. Apolipoprotein B EcoR1 polymorphism showed little variability, one participant had rare genotype A/A, 68.3% had wild type genotype G/G. Conclusion: Observed frequencies of apolipoprotein B XbaI and EcoRI polymorphisms matched other African studies. In spite of low numbers of rare variants, there was positive association between both total cholestrol and high density lipoprotein with ECoR1 wild type G/G genotype, suggesting that ECoRI 4154 G allele could be more protective against coronary heart disease than EcoR1 4154 A allele. There is need for further research at population level to confirm whether apolipoprotein B ECoR1 genotyping is useful for predicting risk of dyslipidemia in HIV patients in our setting. PMID:27790293

  9. [Unique steroid 21-hydroxylase gene CYP21A2 polymorphism in patients with hyperandrogenism signs].

    PubMed

    Barannik, A P; Lavrova, N V; Shilov, I A; Koltunova, A A; Ozolinia, L A; Patrushev, L I

    2012-01-01

    Hyperandrogenism is a medical condition characterized by excessive production of male sex hormones (androgens) in woman organism. One of the major causes of hyperandrogenism is the autosomal-recessive disorder--congenital adrenal hyperplasia (CAH). The mutational defects in the steroid 21-hydroxylase CYP21A2 gene causing steroid 21-hydroxylase deficiency account for over 90% of CAH cases. Our paper describes the sequencing results of entire CYP21A2 gene from 15 patients with hyperandrogenism signs, which had not nine most prevalent mutations associated with nonclassic CAH as it was previously established. 26 polymorphisms were found by sequencing among which 25 were known previously and 23 of them are referred to "normal" gene variants which do not associated with CAH. At the same time the gene of every patient had unique its own distinctive combination of polymorphisms. New SNP represents synonymous substitution C --> T in 3' part of exon 8. All detected SNPs are not regularly distributed but are clustered along the gene. Notably, they were found in the neighborhood of initiation and termination codons and near the intron-exon boundaries of introns 2, 6 and 8. We hypothesize that "normal" clinically insignificant per se SNPs in unique combinations may influence spatial structure of CYP21A2 mRNA or its pre-mRNA splicing efficiency and decrease gene expression level. This assumption may explain the mechanism of pathological phenotype development in our patients.

  10. Phospholipid Biosynthesis Genes and Susceptibility to Obesity: Analysis of Expression and Polymorphisms

    PubMed Central

    Sharma, Neeraj K.; Langberg, Kurt A.; Mondal, Ashis K.; Das, Swapan K.

    2013-01-01

    Recent studies have identified links between phospholipid composition and altered cellular functions in animal models of obesity, but the involvement of phospholipid biosynthesis genes in human obesity are not well understood. We analyzed the transcript of four phospholipid biosynthesis genes in adipose and muscle from 170 subjects. We examined publicly available genome-wide association data from the GIANT and MAGIC cohorts to investigate the association of SNPs in these genes with obesity and glucose homeostasis traits, respectively. Trait-associated SNPs were genotyped to evaluate their roles in regulating expression in adipose. In adipose tissue, expression of PEMT, PCYT1A, and PTDSS2 were positively correlated and PCYT2 was negatively correlated with percent fat mass and body mass index (BMI). Among the polymorphisms in these genes, SNP rs4646404 in PEMT showed the strongest association (p = 3.07E-06) with waist-to-hip ratio (WHR) adjusted for BMI. The WHR-associated intronic SNP rs4646343 in the PEMT gene showed the strongest association with its expression in adipose. Allele “C” of this SNP was associated with higher WHR (p = 2.47E-05) and with higher expression (p = 4.10E-04). Our study shows that the expression of PEMT gene is high in obese insulin-resistant subjects. Intronic cis-regulatory polymorphisms may increase the genetic risk of obesity by modulating PEMT expression. PMID:23724137

  11. Phospholipid biosynthesis genes and susceptibility to obesity: analysis of expression and polymorphisms.

    PubMed

    Sharma, Neeraj K; Langberg, Kurt A; Mondal, Ashis K; Das, Swapan K

    2013-01-01

    Recent studies have identified links between phospholipid composition and altered cellular functions in animal models of obesity, but the involvement of phospholipid biosynthesis genes in human obesity are not well understood. We analyzed the transcript of four phospholipid biosynthesis genes in adipose and muscle from 170 subjects. We examined publicly available genome-wide association data from the GIANT and MAGIC cohorts to investigate the association of SNPs in these genes with obesity and glucose homeostasis traits, respectively. Trait-associated SNPs were genotyped to evaluate their roles in regulating expression in adipose. In adipose tissue, expression of PEMT, PCYT1A, and PTDSS2 were positively correlated and PCYT2 was negatively correlated with percent fat mass and body mass index (BMI). Among the polymorphisms in these genes, SNP rs4646404 in PEMT showed the strongest association (p = 3.07E-06) with waist-to-hip ratio (WHR) adjusted for BMI. The WHR-associated intronic SNP rs4646343 in the PEMT gene showed the strongest association with its expression in adipose. Allele "C" of this SNP was associated with higher WHR (p = 2.47E-05) and with higher expression (p = 4.10E-04). Our study shows that the expression of PEMT gene is high in obese insulin-resistant subjects. Intronic cis-regulatory polymorphisms may increase the genetic risk of obesity by modulating PEMT expression.

  12. Association of Obesity with Proteasomal Gene Polymorphisms in Children

    PubMed Central

    Kupca, Sarmite; Paramonova, Natalija; Sugoka, Olga; Rinkuza, Irena; Trapina, Ilva; Daugule, Ilva; Sipols, Alfred J.; Rumba-Rozenfelde, Ingrida

    2013-01-01

    The aim of this study was to ascertain possible associations between childhood obesity, its anthropometric and clinical parameters, and three loci of proteasomal genes rs2277460 (PSMA6 c.-110C>A), rs1048990 (PSMA6 c.-8C>G), and rs2348071 (PSMA3 c. 543+138G>A) implicated in obesity-related diseases. Obese subjects included 94 otherwise healthy children in Latvia. Loci were genotyped and then analyzed using polymerase chain reactions, with results compared to those of 191 nonobese controls. PSMA3 SNP frequency differences between obese children and controls, while not reaching significance, suggested a trend. These differences, however, proved highly significant (P < 0.002) in the subset of children reporting a family history of obesity. Among obese children denying such history, PSMA6 c.-8C>G SNP differences, while being nonsignificant, likewise suggested a trend in comparison to the nonobese controls. No PSMA6 c.-110C>A SNP differences were detected in the obese group or its subsets. Finally, PSMA3 SNP differences were significantly associated (P < 0.05) with circulating low-density lipoprotein cholesterol (LDL) levels. Our results clearly implicate the PSMA3 gene locus as an obesity risk factor in those Latvian children with a family history of obesity. While being speculative, the clinical results are suggestive of altered circulatory LDL levels playing a possible role in the etiology of obesity in the young. PMID:24455213

  13. 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

  14. Estrogen receptor α gene PvuII polymorphism and coronary artery disease: a meta-analysis of 21 studies*

    PubMed Central

    Ding, Jie; Xu, Hui; Yin, Xiang; Zhang, Fu-rong; Pan, Xiao-ping; Gu, Yi-an; Chen, Jun-zhu; Guo, Xiao-gang

    2014-01-01

    The association between the estrogen receptor α gene (ESR1) PvuII polymorphism (c.454-397T>C) and coronary artery disease (CAD) is controversial. Thus, we conducted a meta-analysis to evaluate the relationship. Data were collected from 21 studies encompassing 9926 CAD patients and 16 710 controls. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the relationship between PvuII polymorphism and CAD. The polymorphism in control populations in all studies followed Hardy-Weinberg equilibrium. We found a significant association between ESR1 PvuII polymorphism and CAD risk in all subjects. When the data were stratified by region, a significant association between ESR1 PvuII polymorphism and CAD risk was observed in Asian populations but not in Western populations. The current study suggests that ESR1 PvuII polymorphism has an important role in CAD susceptibility. PMID:24599688

  15. 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.

  16. β-2 Adrenergic receptor gene polymorphism and response to propranolol in cirrhosis

    PubMed Central

    Kong, De-Run; Wang, Jin-Guang; Sun, Bin; Wang, Ming-Quan; Chen, Chen; Yu, Fang-Fang; Xu, Jian-Ming

    2015-01-01

    AIM: To evaluate the association of β-2 adrenergic receptor (β2-AR) gene polymorphism with response of variceal pressure to propranolol in cirrhosis. METHODS: Sixty-four non-related cirrhotic patients participated in this study and accepted variceal pressure measurement before and after propranolol administration. Polymorphism of the β2-AR gene was determined by directly sequencing of the polymerase chain reaction products from the DNA samples that were prepared from the patients. RESULTS: The prevalence of Gly16-Glu/Gln27 and Arg16-Gln27 homozygotes, and compound heterozygotes was 29.7%, 10.9%, and 59.4%, respectively. Patients with cirrhosis with Gly16-Glu/Gln27 homozygotes had a greater decrease of variceal pressure after propranolol administration than those with Arg16-Gln27 homozygotes or with compound heterozygotes (22.4% ± 2.1%, 13.1% ± 2.7% and 12.5% ± 3.1%, respectively, P < 0.01). CONCLUSION: The variceal pressure response to propranolol was associated with polymorphism of β2-AR gene. Patients with the Gly16-Glu/Gln27 homozygotes probably benefit from propranolol therapy. PMID:26109805

  17. 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

  18. 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

  19. Emotional modulation of muscle pain is associated with polymorphisms in the serotonin transporter gene.

    PubMed

    Horjales-Araujo, Emilia; Demontis, Ditte; Lund, Ellen Kielland; Vase, Lene; Finnerup, Nanna Brix; Børglum, Anders D; Jensen, Troels Staehelin; Svensson, Peter

    2013-08-01

    The perception of pain is determined by a combination of genetic, neurobiological, cultural, and emotional factors. Recent studies have demonstrated an association between specific genotypes and pain perception. Particular focus has been given to the triallelic polymorphism in the promoter region of the serotonin transporter gene in relation to pain perception. The aim of this study was to investigate whether the modulatory effect of emotions mediated by visual stimuli on muscular pain perception is genotype dependent. A total of 150 healthy subjects were selected on the basis of their polymorphism in the serotonin transporter gene. First, visual conditioning was performed with positive, negative, and neutral pictures from the International Affective Picture System, and the unpleasantness/pleasantness of the pictures was rated. Second, visual conditioning stimuli were presented while experimental jaw muscle pain was evoked by injection of hypertonic saline into the masseter muscle, and participants continuously rated pain intensity on an electronic visual analogue scale. The pictures induced similar changes in emotions across the 3 genotype groups, and hypertonic saline evoked moderate pain levels in all participants. However, in participants with a high expression of the serotonin transporter protein, conditioning with negative pictures increased pain intensity and positive pictures decreased pain intensity when compared with neutral pictures. In contrast, there were no significant effects of the pictures on pain perception in participants with either intermediate or low expression of the protein. These results suggest that polymorphisms in the serotonin transporter gene play an important role in emotions modulation of muscle pain.

  20. 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

  1. Association of interleukin-18 gene polymorphism with body mass index in women

    PubMed Central

    2012-01-01

    Background Interleukin (IL)-18 is an important regulator of innate and acquired immune responses and has multiple roles in chronic inflammation and autoimmune disorders. Obesity is characterized by low- grade chronic inflammation. IL-18 has been suggested as an adipogenic cytokine that is associated with excess adiposity. The purpose of this study is to evaluate the relationship between IL-18 gene polymorphisms (−137 G/C and −607 C/A) and obesity. Methods All 680 subjects were genotyped for the polymorphisms of IL-18 gene promoters (at positions −137 G/C and −607 C/A) using a polymerase chain reaction (271 cases with BMI ≥25 kg/m2 and 409 controls with BMI <25 kg/m2). A chi-square test was used to compare the genotype and allele frequencies between the cases and control populations. Results Analyses of the genotype distributions revealed that IL-18 –607 C/A polymorphism was associated with an increase in body mass index in obese women in the Korean population (chi(2) = 12.301, df = 2, p = 0.015). Conclusion Carriage of the A allele at position −607 in the promoter of the IL-18 gene may have a role in the development of obesity. PMID:22531046

  2. Polymorphisms in the XPC gene and gastric cancer susceptibility in a Southern Chinese population

    PubMed Central

    Hua, Rui-Xi; Zhuo, Zhen-Jian; Shen, Guo-Ping; Zhu, Jinhong; Zhang, Shao-Dan; Xue, Wen-Qiong; Li, Xi-Zhao; Zhang, Pei-Fen; He, Jing; Jia, Wei-Hua

    2016-01-01

    Previous studies have reported that XPC gene polymorphisms may modify the individual susceptibility to gastric cancer. In this case–control study with a total of 1,142 cases and 1,173 controls, four potentially functional polymorphisms were genotyped in the XPC gene (rs2228001 A>C, rs2228000 C>T, rs2607775 C>G, and rs1870134 G>C) by Taqman assays and their associations were analyzed with the risk of gastric cancer in a Southern Chinese population. No significant association between any of XPC polymorphisms and gastric cancer risk was detected except for a borderline association with the rs2228000 CT/TT genotype (crude odds ratio =0.86, 95% confidence interval =0.73–1.02, P=0.088) when compared to the rs2228000 CC genotype. Further stratified analysis revealed that the protective effect of rs2228000 CT/TT on the risk of gastric cancer was only significant among subjects older than 58 years. In summary, results indicated that genetic variations in XPC gene may play a weak effect on gastric cancer susceptibility in Southern Chinese population, which warrants further confirmation in larger prospective studies with different ethnic populations.

  3. Polymorphisms in the XPC gene and gastric cancer susceptibility in a Southern Chinese population.

    PubMed

    Hua, Rui-Xi; Zhuo, Zhen-Jian; Shen, Guo-Ping; Zhu, Jinhong; Zhang, Shao-Dan; Xue, Wen-Qiong; Li, Xi-Zhao; Zhang, Pei-Fen; He, Jing; Jia, Wei-Hua

    2016-01-01

    Previous studies have reported that XPC gene polymorphisms may modify the individual susceptibility to gastric cancer. In this case-control study with a total of 1,142 cases and 1,173 controls, four potentially functional polymorphisms were genotyped in the XPC gene (rs2228001 A>C, rs2228000 C>T, rs2607775 C>G, and rs1870134 G>C) by Taqman assays and their associations were analyzed with the risk of gastric cancer in a Southern Chinese population. No significant association between any of XPC polymorphisms and gastric cancer risk was detected except for a borderline association with the rs2228000 CT/TT genotype (crude odds ratio =0.86, 95% confidence interval =0.73-1.02, P=0.088) when compared to the rs2228000 CC genotype. Further stratified analysis revealed that the protective effect of rs2228000 CT/TT on the risk of gastric cancer was only significant among subjects older than 58 years. In summary, results indicated that genetic variations in XPC gene may play a weak effect on gastric cancer susceptibility in Southern Chinese population, which warrants further confirmation in larger prospective studies with different ethnic populations. PMID:27660469

  4. Ala-9Val polymorphism of Mn-SOD gene in sickle cell anemia.

    PubMed

    Sogut, S; Yonden, Z; Kaya, H; Oktar, S; Tutanc, M; Yilmaz, H R; Yigit, A; Ozcelik, N; Gali, E

    2011-01-01

    Oxidative stress may be contributory to the pathophysiology of the abnormalities that underlie the clinical course of sickle cell anemia. We looked for a possible genetic association between the functional polymorphism Ala-9Val in the human Mn-SOD gene and sickle cell anemia. One hundred and twenty-seven patients with sickle cell anemia and 127 healthy controls were recruited into the study. Alanine versus valine polymorphism in the signal peptide of the Mn-SOD gene was evaluated using a primer pair to amplify a 107-bp fragment followed by digestion with the restriction enzyme NgoMIV. In the sickle cell anemia patients, the frequency of Val/Val genotype was approximately 1.4-fold lower and that of Ala/Val was 1.3-fold higher compared to the controls. No significant difference in genotype frequencies was found between patients and controls (χ(2) = 4.561, d.f. = 2, P = 0.101). The Val-9 was the most common allele in patient and healthy subjects. No significant difference in allele frequencies was found between patients and controls (χ(2) = 1.496, d.f. = 1, P = 0.221). We conclude that the Mn-SOD gene polymorphism is not associated with sickle cell anemia. PMID:21574139

  5. The Association of Transporter Genes Polymorphisms and Lung Cancer Chemotherapy Response

    PubMed Central

    Wang, Ying; Yin, Ji-Ye; Li, Xiang-Ping; Chen, Juan; Qian, Chen-Yue; Zheng, Yi; Fu, Yi-Lan; Chen, Zi-Yu; Zhou, Hong-Hao; Liu, Zhao-Qian

    2014-01-01

    Lung cancer is one of the most common cancers and is the leading cause of death worldwide. Platinum-based chemotherapy is the main treatment method in lung cancer patients. Our previous studies indicated that single nucleotide polymorphisms (SNPs) in some transporter genes played important role in platinum-based chemotherapy efficacy. The aim of this study was to investigate the association of SNPs in transporter genes and platinum-based chemotherapy efficacy. The main polymorphisms on transporters OCT2, LRP, AQP2, AQP9 and TMEM205 genes were genotyped in 338 lung cancer patients. The rs195854 in genotypic model, rs896412 in genotypic and recessive models for all subjects showed significant association with chemotherapy response. In stratification analysis, TMEM205 rs896412, OCT2 rs1869641 and rs195854, AQP9 rs1516400 and AQP2 rs7314734 showed significant relation to chemotherapy response. In conclusion, the genetic polymorphisms in OCT2, AQP2, AQP9 and TMEM205 may contribute to chemotherapy response in lung cancer patients. PMID:24643204

  6. 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

  7. Investigation on the role of XPG gene polymorphisms in breast cancer risk in a Chinese population.

    PubMed

    Ma, S H; Ling, F H; Sun, Y X; Chen, S F; Li, Z

    2016-01-01

    We conducted a case-control study to investigate the role of XPG gene polymorphisms (rs2094258, rs751402, and rs17655) in the development of breast cancer. Patients with breast cancer (320) and control subjects (294) were consecutively selected from the Zhongshan Hospital between April 2013 and January 2015. The genotyping of XPG rs2094258, rs751402, and rs17655 was performed using polymerase chain reaction-restriction fragment length polymorphism. Using the chi-square test, we did not find any significant differences in the genotype distributions of XPG rs2094258 (χ(2) = 1.48, P = 0.48), rs751402 (χ(2) = 0.65, P = 0.72), and rs17655 (χ(2) = 0.01, P = 0.92) genes between breast cancer patients and control subjects. The genotype distributions of XPG rs2094258, rs751402, and rs17655 did not deviate from the Hardy-Weinberg equilibrium in control subjects, and the P values were 0.58, 0.97, and 0.26, respectively. Using unconditional logistic regression analysis, we found that XPG rs2094258, rs751402 and rs17655 gene polymorphisms are not associated with the development of breast cancer after adjusting for potential confounding factors. In conclusion, we found that XPG rs2094258, rs751402, and rs17655 do not influence the development of breast cancer in a Chinese population. PMID:27323134

  8. Polymorphisms in the XPC gene and gastric cancer susceptibility in a Southern Chinese population

    PubMed Central

    Hua, Rui-Xi; Zhuo, Zhen-Jian; Shen, Guo-Ping; Zhu, Jinhong; Zhang, Shao-Dan; Xue, Wen-Qiong; Li, Xi-Zhao; Zhang, Pei-Fen; He, Jing; Jia, Wei-Hua

    2016-01-01

    Previous studies have reported that XPC gene polymorphisms may modify the individual susceptibility to gastric cancer. In this case–control study with a total of 1,142 cases and 1,173 controls, four potentially functional polymorphisms were genotyped in the XPC gene (rs2228001 A>C, rs2228000 C>T, rs2607775 C>G, and rs1870134 G>C) by Taqman assays and their associations were analyzed with the risk of gastric cancer in a Southern Chinese population. No significant association between any of XPC polymorphisms and gastric cancer risk was detected except for a borderline association with the rs2228000 CT/TT genotype (crude odds ratio =0.86, 95% confidence interval =0.73–1.02, P=0.088) when compared to the rs2228000 CC genotype. Further stratified analysis revealed that the protective effect of rs2228000 CT/TT on the risk of gastric cancer was only significant among subjects older than 58 years. In summary, results indicated that genetic variations in XPC gene may play a weak effect on gastric cancer susceptibility in Southern Chinese population, which warrants further confirmation in larger prospective studies with different ethnic populations. PMID:27660469

  9. 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

  10. Relationship between p53 gene codon-72 polymorphisms and hypertrophic scar formation following caesarean section.

    PubMed

    Gao, Jianhua; Chen, Ying; Liao, Nong; Zhao, Wei; Zeng, Weisen; Li, Yingtao; Wang, Shaojing; Lu, Feng

    2014-05-01

    The aim of the present study was to determine the relationship between p53 gene codon-72 polymorphisms and hypertrophic scar formation following caesarean section (CS). Blood samples from 260 female patients were collected one week following a CS for the detection of p53 gene polymorphisms using a molecular beacon-coupled quantitative polymerase chain reaction technique. Patients had follow-ups for 12-18 months to observe the scar formation. From these observations, the relationship between the p53 codon-72 polymorphisms and hypertrophic scar formation occurrence was investigated. Among the patients with the CCC/CCC genotype, nine patients had hypertrophic scars and 46 patients showed normal healing, which is a ratio of 0.19. However, the follow-up investigations indicated that the presence of a homozygous or heterozygous C-to-G alteration at the codon-72 site in gene p53 resulted in 13 patients with hypertrophic scars and 192 patients with normal healing, which is a ratio of 0.07. Therefore, these results indicate that patients with the CCC/CCC genotype had a higher risk of developing hypertrophic scars compared with that for patients with the CCC/CGC or CGC/CGC genotypes.

  11. Association of IL-8 (-251 A/T) Gene Polymorphism with Clinical Parameters and Chronic Periodontitis

    PubMed Central

    Khosropanah, Hengameh; Sarvestani, Eskandar Kamali; Mahmoodi, Ashkan; Golshah, Masoud

    2013-01-01

    Objective: To investigate the correlation between IL-8 (-251 A/T) gene polymorphism and susceptibility to chronic periodontitis as well as different clinical parameters and severity of the condition in patients referred to dental school, Shiraz University of Medical Sciences, Shiraz, Iran. Materials and Methods: In this randomized cross sectional study, 227 non-smoking patients with chronic periodontitis (test) and 40 healthy individuals (control) were enrolled in this experiment and the following clinical parameters were employed in the study: Periodontal Pocket Depth (PPD), Clinical Attachment Level (CAL) and Bone Loss (BL). All participants underwent the PCR (Polymerase Chain Reaction) test to detect 251 A/T Single Nucleotide Polymorphism of IL8 gene. Results: No significant correlation was perceived between different genotypes of IL-8 and the severity of the periodontal condition (P= 0.164), neither did we detect any substantial association between different IL-8 genotypes and the mean PPD (P=0.525), CAL (P=0.151), BL (P=0.255), PI (P=0.087), BOP (P=0.265) and the average number of teeth (P=0.931). Conclusion: The results implied that there was no explicit correlation between 251 (A/T) IL-8 gene polymorphism and the severity of the chronic periodontal disease or to the susceptibility to it. PMID:24396350

  12. Genetic Polymorphisms in DNA Repair Genes as Modulators of Hodgkin Disease Risk

    PubMed Central

    El-Zein, Randa; Monroy, Claudia M.; Etzel, Carol J.; Cortes, Andrea C.; Xing, Yun; Collier, Amanda L.; Strom, Sara S.

    2009-01-01

    BACKGROUND Although the pathogenesis of Hodgkin disease (HD) remains unknown, the results of epidemiologic studies suggest that heritable factors are important in terms of susceptibility. Polymorphisms in DNA repair genes may contribute to individual susceptibility for development of different cancers. However, to the authors’ knowledge, few studies to date have investigated the role of such polymorphisms as risk factors for development of HD. METHODS The authors evaluated the relation between polymorphisms in 3 nucleotide excision repair pathway genes (XPD [Lys751Gln], XPC [Lys939Gln], and XPG [Asp1104His]), the base excision repair XRCC1 (Arg399Gln), and double-strand break repair XRCC3 (Thr241Met) in a population of 200 HD cases and 220 matched controls. Variants were investigated independently and in combination; odd ratios (OR) were calculated. RESULTS A positive association was found for XRCC1 gene polymorphism Arg399Gln (OR, 1.77; 95% confidence interval [95% CI], 1.16−2.71) and risk of HD. The combined analysis demonstrated that XRCC1/XRCC3 and XRCC1/XPC polymorphisms were associated with a significant increase in HD risk. XRCC1 Arg/Arg and XRCC3 Thr/Met genotypes combined were associated with an OR of 2.38 (95% CI, 1.24−4.55). The XRCC1 Arg/Gln and XRCC3 Thr/Thr, Thr/Met, and Met/Met genotypes had ORs of 1.88 (95% CI, 1.02−4.10), 1.97 (95% CI, 1.05−3.73), and 4.13 (95% CI, 1.50−11.33), respectively. XRCC1 Gln/Gln and XRCC3 Thr/Thr variant led to a significant increase in risk, with ORs of 3.00 (95% CI, 1.15−7.80). Similarly, XRCC1 Arg/Gln together with XPC Lys/Lys was found to significantly increase the risk of HD (OR, 2.14; 95% CI, 1.09−4.23). CONCLUSIONS These data suggest that genetic polymorphisms in DNA repair genes may modify the risk of HD, especially when interactions between the pathways are considered. PMID:19280628

  13. Autophagy gene polymorphism is associated with susceptibility to leprosy by affecting inflammatory cytokines.

    PubMed

    Yang, Degang; Chen, Jia; Shi, Chao; Jing, Zhichun; Song, Ningjing

    2014-04-01

    Autophagy and inflammation closely interact with each other, and together, they play critical roles in bacterial infection. Leprosy is caused by the infection of Mycobacterium leprae (M. leprae). The objective of the study was to investigate the association between polymorphisms in IRGM, an autophagy gene, and susceptibility to leprosy, and identify possible functions of the polymorphism in the infection of M. leprae. Two polymorphisms in IRGM, rs4958842 and rs13361189, were tested in 412 leprosy cases and 432 healthy controls. Levels of inflammatory cytokines including interleukin 1 beta, IL-4, IL-6, and interferon gamma (INF-γ) were measured after the infection of M. leprae in the peripheral blood mononuclear cell (PBMC) of subjects with different genotypes of rs13361189. Data showed that prevalence of rs13361189TC and CC genotypes were significantly higher in leprosy patients than in healthy controls (odds ratio (OR) = 1.49, 95 % confidence interval (CI) 1.09-2.04, P = 0.012; OR = 2.58, 95 % CI 1.65-4.05, P < 0.001; respectively). Furthermore, the frequency of rs13361189CC genotype was increased in patients with complications than those without complications (P = 0.011). When analyzing the effect of rs13361189 polymorphism on M. leprae infection, we identified that M. leprae-infected PBMC with rs13361189CC genotype expressed significantly elevated levels of INF-γ and IL-4 than those with TT genotype. Our results suggested autophagy gene polymorphism was associated with the increased risk of leprosy by affecting inflammatory cytokines.

  14. Diversity and characterization of polymorphic 5' promoter haplotypes of MICA and MICB genes.

    PubMed

    Cox, S T; Madrigal, J A; Saudemont, A

    2014-09-01

    The major histocompatibility complex (MHC) class I-related chain A (MICA) and B (MICB) are ligands for the natural killer group 2, member D (NKG2D) activating receptor expressed on natural killer (NK) cells, natural killer T (NKT) cells, CD8+ T cells and γδ T cells. Natural killer group 2, member D (NKG2D) ligand expression is stress-related and upregulated by infected or oncogenic cells leading to cytolysis. MICA and MICB genes display considerable polymorphism among individuals and studies have investigated allelic association with disease and relevance of MICA in transplantation, with variable success. It is now known that promoters of MICA and MICB are polymorphic with some polymorphisms associating with reduced expression. We sequenced International Histocompatibility Workshop (IHW) cell line DNA to determine promoter types and alleles encoded by exons 2-6. We found 8 of 12 known MICA promoter polymorphisms and although promoter P7 dominated, other promoters associated with the same allele. For example, MICA*002:01 had promoters P3, P4 or P7 and the common MICA*008:01/04 type had P1, P6 or P7. Similarly, we sequenced 8 of 12 known MICB promoter haplotypes. Some coding region defined MICB alleles had a single promoter, for example, MICB*002:01 and promoter P9, whereas the promiscuous MICB*005 allele had promoters P1, P2, P5, P6, P10 or P12. The results indicate potential for variation in expression of MICA and MICB ligands between individuals with the same allelic types. If differential expression by polymorphic MICA and MICB promoters is confirmed by functional studies, involvement of these genes in disease susceptibility or adverse transplantation outcomes may require knowledge of both promoter and allelic types to make meaningful conclusions.

  15. 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

  16. Interaction of DNA repair gene polymorphisms and aflatoxin B1 in the risk of hepatocellular carcinoma

    PubMed Central

    Yao, Jin-Guang; Huang, Xiao-Ying; Long, Xi-Dai

    2014-01-01

    Aflatoxin B1 (AFB1) is an important environmental carcinogen and can induce DNA damage and involve in the carcinogenesis of hepatocellular carcinoma (HCC). The deficiency of DNA repair capacity related to the polymorphisms of DNA repair genes might play a central role in the process of HCC tumorigenesis. However, the interaction of DNA repair gene polymorphisms and AFB1 in the risk of hepatocellular carcinoma has not been elucidated. In this study, we investigated whether six polymorphisms (including rs25487, rs861539, rs7003908, rs28383151, rs13181, and rs2228001) in DNA repair genes (XPC, XRCC4, XRCC1, XRCC4, XPD, XRCC7, and XRCC3) interacted with AFB1, and the gene-environmental interactive role in the risk of HCC using hospital-based case-control study (including 1486 HCC cases and 1996 controls). Genotypes of DNA repair genes were tested using TaqMan-PCR technique. Higher AFB1 exposure was observed among HCC patients versus the control group [odds ratio (OR) = 2.08 for medium AFB1 exposure level and OR = 6.52 for high AFB1 exposure level]. Increasing risk of HCC was also observed in these with the mutants of DNA repair genes (risk values were from 1.57 to 5.86). Furthermore, these risk roles would be more noticeable under the conditions of two variables, and positive interactive effects were proved in the followed multiplicative interaction analysis. These results suggested that DNA repair risk genotypes might interact with AFB1 in the risk of HCC. PMID:25337275

  17. Immunopathogenesis of dengue hemorrhagic fever and shock syndrome: role of TAP and HPA gene polymorphism.

    PubMed

    Soundravally, R; Hoti, S L

    2007-12-01

    Clinical outcomes of dengue infection such as dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) could be attributed to host genetic factors. The transporters associated with antigen processing (TAP) genes are polymorphic genes located in the human leukocyte antigen (HLA) class II region and are essentially involved in class I antigen presentation. Therefore, these genes might grant susceptibility to severe dengue infection. Hence, the aim of the study was to type the TAP1 gene (using amplification refraction mutation system [ARMS] polymerase chain reaction [PCR]) and HPA1 and HPA2 gene polymorphism (by PCR-sequence specific primers) in different clinical spectrums of dengue infection. The study included 100 controls and 91 DF, 75 DHF, and 32 DSS patients. The results revealed that the frequencies of valine at TAP1 333 and HPA 1b at HPA1 were increased among DHF and DSS, respectively, in comparison to controls (p <0.05). The frequency of genotype TAP1 333 ILE/VAL (61.3%) was significantly higher in DHF compared with control (37%, p = 0.005) or DF (38.9%, p = 0.007) patients. A significantly greater proportion of DHF patients demonstrated HPA1a/1a and HPA 2a/2b genotypes than DF patients. DSS patients were more likely to be heterozygous at HPA1 than DHF (OR = 4.75, p = 0.003). A positive correlation existed between TAP1 333 and HPA1 in DHF (p = 0.017, r = 0.229). This first report on TAP and HPA gene polymorphism in dengue suggested that the heterozygous pattern at the TAP1 333 locus and HPA1a/1a and HPA2a/2b genotypes confer susceptibility to DHF and the HPA1a/1b genotype was determined to be a genetic risk factor for DSS.

  18. Polymorphism and expression of isoflavone synthase genes from soybean cultivars.

    PubMed

    Kim, Hyo-Kyoung; Jang, Yun-Hee; Baek, Il-Sun; Lee, Jeong-Hwan; Park, Min Joo; Chung, Young-Soo; Chung, Jong-Il; Kim, Jeong-Kook

    2005-02-28

    Isoflavones are synthesized by isoflavone synthases via the phenylpropanoid pathway in legumes. We have cloned two isoflavone synthase genes, IFS1 and IFS2, from a total of 18 soybean cultivars. The amino acid residues of the proteins that differed between cultivars were dispersed over the entire coding region. However, amino acid sequence variation did not occur in conserved domains such as the ERR triad region, except that one conserved amino acid was changed in the IFS2 protein of the GS12 cultivar (R374G) and the IFS1 proteins of the 99M06 and Soja99s65 cultivars (A109T, F105I). In three cultivars (99M06, 99M116, and Simheukpi), most of amino acid changes were such that the difference between the amino acid sequences of IFS1 and IFS2 was reduced. The expression profiles of three enzymes that convert naringenin to the isoflavone, genistein, chalcone isomerase (CHI), isoflavone synthase (IFS) and flavanone 3-hydroxylase (F3H) were examined. In general, IFS mRNA was more abundant in etiolated seedlings than mature plants whereas the levels of CHI and F3H mRNAs were similar in the two stages. During seed development, IFS was expressed a little later than CHI and F3H but expression of these three genes was barely detectable, if at all, during later seed hardening. In addition, we found that the levels of CHI, F3H, and IFS mRNAs were under circadian control. We also showed that IFS was induced by wounding and by application of methyl jasmonate to etiolated soybean seedlings. PMID:15750342

  19. Tumor necrosis factor and interleukin-6 gene polymorphisms and endometriosis risk in Asians: a systematic review and meta-analysis.

    PubMed

    Li, Jie; Chen, Yang; Wei, Shixiu; Wu, Hongbo; Liu, Chengjun; Huang, Qiaoying; Li, Liuming; Hu, Yanling

    2014-03-01

    A relationship between endometriosis and tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) gene polymorphisms has been raised for Asians. However, this topic is controversial. This study was a meta-analysis to explore whether TNF-α/IL-6 gene polymorphisms were associated with a risk of endometriosis in Asians. By searching PubMed, HuGENet, and China National Knowledge Infrastructure (CNKI) databases, 17 studies were identified and included (3372 cases and 4008 controls). The odds ratio (OR) with 95% confidence interval (CI) was used to assess the association between TNF-α/IL-6 gene polymorphisms and endometriosis risk. An association of TNF-α gene -1031T/C polymorphism with endometriosis was found (TT + TC vs. CC: OR 0.50, 95% CI 0.30-0.82, I(2) = 37.1%, P = 0.20; TT vs. CC: OR 0.50, 95% CI 0.30-0.82, I(2) = 43.0%, P = 0.173; TC vs. CC: OR 0.49, 95% CI 0.29-0.83, I(2) = 10.6%, P = 0.327). In addition, TNF-α-238A/G and IL-6 -174C/G gene polymorphisms were also likely to be associated with endometriosis in Asians. For the TNF-α-238A/G gene polymorphism, the OR was 1.577 (95% CI: 1.01-2.48). For the IL-6 -174C/G gene polymorphism, the OR was 1.554 (95% CI: 1.04-2.31). No associations were detected between the TNF-α-308A/G and IL-6 -634C/G polymorphisms and susceptibility to endometriosis. Our results indicate that the TNF-α gene -1031T/C polymorphism can reduce the risk of endometriosis, but for Asians, TNF-α-238A/G and IL-6 -174C/G gene polymorphisms may be a risk factor for endometriosis. No association was found for the TNF-α-308A/G and IL-6 -634C/G gene polymorphisms.

  20. Functional polymorphisms in the matrix metalloproteinase genes and their association with bladder cancer risk and recurrence: a mini-review.

    PubMed

    Wieczorek, Edyta; Wasowicz, Wojciech; Gromadzinska, Jolanta; Reszka, Edyta

    2014-08-01

    Molecular pathogenesis of muscle invasive bladder cancer and non-muscle invasive bladder cancer is incompletely elucidated. It is believed that matrix metalloproteinases, which are involved in the processes of uncontrolled extracellular matrix substrates degradation and participate in modulating the activity of a variety of non-matrix proteins, can contribute to carcinogenesis. Polymorphisms in the MMP genes associated with unique genomic changes in bladder cancer patients are still being investigated to discover direct links with pathophysiological mechanisms. Because of the functional polymorphisms in the MMP genes, which have a proven or likely effect on their protein expression, they could possibly affect the tumor process. The current mini-review synthesizes findings regarding the association of genetic polymorphisms in the MMP genes with bladder cancer risk and recurrence in patients. We discuss the current views on the feasibility of genetic polymorphisms in the MMP1, 2, 3, 7, 8, 9 and 12 genes as a risk, and prognostic markers for patients with bladder cancer. The majority of the research described in the present mini-review proves that the genetic polymorphism in the MMP1 (rs1799750) is the most widely studied, and suggests that the rare genotype, 2G2G, of that gene might show increased susceptibility for bladder cancer, especially among smokers. However, existing statistically significant associations between the genetic polymorphisms in the MMP genes and bladder cancer risk have not been clearly shown, and further studies are necessary in order to positively confirm them or dispel potential false hopes. PMID:24635493

  1. 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.

  2. Functional relevance of DNA polymorphisms within the promoter region of the prion protein gene and their association to BSE infection.

    PubMed

    Kashkevich, Kseniya; Humeny, Andreas; Ziegler, Ute; Groschup, Martin H; Nicken, Petra; Leeb, Tosso; Fischer, Christine; Becker, Cord-Michael; Schiebel, Katrin

    2007-05-01

    Transmissible spongiform encepha