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Association Between Two Common Polymorphisms of Vitamin D Binding Protein and the Risk of Coronary Artery Disease: A Case-control Study.

ABSTRACT: Background:Coronary Artery Disease (CAD) is one of the most widespread non-communicable diseases. Vitamin Dbinding protein (VDBP) and its genetic poly morphisms have been highlighted as the susceptible components for CAD. The aim of the present study was to examine the association of VDBP single nucleotide poly morphisms (SNPs) - rs7041 and rs4588 - with CAD susceptibility among the Iranian population. Methods:A total of 143 men with CAD and 145 healthy age-sex matched controls underwent genotyping for the - rs7041 and rs4588 polymorphisms using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Serum level of 25(OH)D was assayed using microplate colorimetric enzyme immunoassay. Results:We found a significant association between GG genotype (rs7041) and CAD (p=0.02, OR=0.537 95% CI =0.306-0.944). Regarding rs4588 polymorphism, a significant difference was observed in which the CA genotype (p=0.00032, OR=2.578, 95% CI=1.579-4.208) and allele A (P=0.028, OR=1.491, 95% CI=1.043-2.132) were significantly higher in CAD patients compared to controls. In spite of lower serum levels of 25(OH)D in CAD patients, we found no significant association between these SNPs and Vitamin D serum concentrations. Conclusion:We concluded that VDBP polymorphisms affect the susceptibility to CAD in Iranian men. Therefore, further studies are required to clarify the association of VDBP phenotypes and its serum levels with CAD.

SUBMITTER: Tarighi S

PROVIDER: S-EPMC6294082 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Association Between Two Common Polymorphisms of Vitamin D Binding Protein and the Risk of Coronary Artery Disease: A Case-control Study.

Tarighi Shahriar S Najafi Mahdi M Hossein-Nezhad Arash A Ghaedi Hamid H Meshkani Reza R Moradi Nariman N Fadaei Reza R Kazerouni Faranak F Shanaki Mehrnoosh M

Journal of medical biochemistry 20171028 4

<h4>Background</h4>Coronary Artery Disease (CAD) is one of the most widespread non-communicable diseases. Vitamin Dbinding protein (VDBP) and its genetic poly morphisms have been highlighted as the susceptible components for CAD. The aim of the present study was to examine the association of VDBP single nucleotide poly morphisms (SNPs) - rs7041 and rs4588 - with CAD susceptibility among the Iranian population.<h4>Methods</h4>A total of 143 men with CAD and 145 healthy age-sex matched controls un ...[more]

PMID: 30581332

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Project description:BackgroundStudies on the susceptibility of vitamin D receptor (VDR) polymorphisms to coronary artery disease (CAD) reached controversial results. We performed this study for a more accurate evaluation between the VDR polymorphisms and CAD susceptibility.MethodsPubMed, Embase, CNKI, Wan Fang, and VIP databases were searched. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to evaluate the associations. Trial sequential analysis (TSA) was introduced to estimate the positive associations. The potential functions of the VDR polymorphisms were analyzed based on the SNPinfo and ENSEMBL databases.ResultsThirteen studies were finally included. In the overall analysis, increased CAD risks were observed in the VDR rs1544410 polymorphism and verified by the TSA; for the rs2228570 and rs731236 polymorphisms, significant associations with high heterogeneity were detected; decreased risk was remarkably observed for the rs7975232 polymorphism. In the subgroup analysis, wide associations with reduced heterogeneity were observed in the rs2228570, rs1544410, and rs731236 polymorphisms. The RNAfold analysis indicated the mutant G allele of the rs1544410 polymorphism was easier to disperse from the DNA double helix structure and may have a potential crucial role in the VDR transcription process.ConclusionsOur analysis supports the role of the rs1544410 polymorphism in the VDR gene as a risk factor for CAD. The VDR rs2228570 and rs731236 polymorphisms were associated with increased CAD risks in the White population. Restrict decreased CAD risk was firstly discovered in the rs7975232 polymorphism.LimitationsFirstly, the language was restricted to English and Chinese, which will cause the limited number of studies included; secondly, other unknown polymorphisms in VDR polymorphisms could also be associated the CAD susceptibility, and more case-control studies with comprehensive clinical outcomes and GWAS studies were required; thirdly, the rs1544410, rs7975232 and rs731236 polymorphism are in strong LD, haploid factors with CAD risk need to be considered; fourthly, the mechanisms of the VDR polymorphism on the VDR gene or RNA or protein were not discussed enough, further mechanistic studies are required; at last, genetic factor was the one side for CAD susceptibility, the interaction between environmental risk factors should be considered.

Project description:Background Genome wide association studies (GWAS) have successfully revealed >40 genetic risk loci associated with coronary artery disease (CAD) in Europeans. Only five loci have been replicated in South Asians. Methods We assessed the association of 47 genome-wide significant single-nucleotide polymorphisms (SNPs) with CAD in a Pakistani sample comprising of 663 clinically ascertained and angiographically confirmed cases and controls. Genotypes were performed using Sequenom’s iPLEX assay. The association of selected SNPs with coronary stenosis was initially determined by chi-square and additive genetic model. We selected 12 SNPs based on additive model and their association was also analyzed by using dominant model. All statistical analyses were performed by R software. Linkage disequilibrium (LD) of significant SNPs was determined by SNAP web portal and functional annotation of SNPs was determined by RegulomeDB. Results We had five significant SNPs out of 47 variants (rs4252120; P=0.003, rs2505083; P=0.006, rs2048327; P=0.04, rs602633; P=0.02 & rs46522; P=0.02) under dominant model and two, PLG/rs4252120 (P=0.003) and KIAA1462/rs2505083 (P=0.006), showed significant association with CAD in our sample after correcting for multiple testing (q<0.05). The odds ratio (OR) in cases vs. controls for two significant SNPs were; [PLG/rs4252120 (OR =1.83; P=0.003, FDR =0.02)] and [KIAA1462/rs2505083 (OR =1.65, P=0.006, FDR =0.03)]. PLG/rs4252120 was in LD with two other functional PLG variants (rs4252126 and rs4252135) having RegulomeDB score of 1f. Likewise, KIAA1462/rs2505083 was in LD with a functional SNP KIAA1462/rs3739998 having RegulomeDB score of 2b (likely affects TF binding). Conclusions We have successfully replicated two previously reported genome-wide significant SNPs in our Pakistani sample. KIAA1462/rs2505083 appears to be functional by itself as well as proxy of a functional SNP (KIAA1462/rs3739998). PLG/rs4252120 is proxy of two functional SNPs. Further association studies in other non-European populations and future functional studies are warranted to assess the impact of these two variants on risk of CAD.

Project description:Lipoprotein(a) is a well-known independent risk factor for coronary artery disease (CAD) and primarily determined by variation in the LPA gene coding for the apolipoprotein(a) moiety. Our study purpose was to evaluate the association between the human LPA gene polymorphisms and CAD in Han and Uyghur populations in Xinjiang, China. A case-control study was conducted with 831 Han people (392 CAD patients and 439 control subjects) and 829 Uygur people (513 CAD patients and 316 control subjects). All participants were genotyped for the same 3 single nucleotide polymorphisms (rs1801693, rs6923877, and rs9364559) of the LPA gene by a Real-time PCR instrument. In CAD patients, the levels of lipoprotein(a) were significantly higher in the Han population with the C/C genotype at the rs1801693 (P = .018) and the A/A genotype at the rs9364559 (P = .029) than in the Uyghur population. The polymorphisms rs1801693, rs6923877, and rs9364559 were found to be associated with CAD in the Han population. For men, the distribution of rs1801693 in genotypes, alleles and recessive model (CC vs CT + TT) showed a significant difference (all P < .05), and the difference in recessive model was retained after adjustment for covariates (odds ratio [OR]: 0.557, 95% confidence interval [CI]: 0.355-0.874, P = .011). But the distribution of rs6923877 in genotypes and dominant model (GG vs AG + AA) showed a significant difference (both P < .05) in both men and women, and the difference was kept in dominant model after adjustment (OR: 1.473, 95% CI:1.009-2.148, P = .045). For women, a significant difference was found in the distribution of rs9364559 in the alleles and dominant model (AA vs AG + GG) (for alleles: P = .021, for dominant model: P = .025, OR: 0.560, 95% CI:0.350-0.898, P = .016) after adjustment. Polymorphisms rs1801693, rs6923877, and rs9364559 of the LPA gene are associated with CAD in the Han population in Xinjiang Uygur Autonomous Region of China.

Project description:Background: Coronary artery disease (CAD) is one of the main fatal diseases all over the world. CAD is a complex disease, which has multiple risk factors mechanisms. In recent years, genome-wide association study (GWAS) had revealed single nucleotide polymorphism genes (SNPs) which were closely related with CAD risks. The relationship between long non-coding RNA (lncRNA) MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) and CAD risk is largely unknown. To our knowledge, this is the first study which demonstrated the interaction effects of SNP-SNP and SNP-environment with CAD risk. In general, our case-control study is to detect the association between MALAT1 (rs619586, rs4102217) SNPs and CAD risk. Methods: Three hundred and sixty-five CAD patients and three hundred and eighty-four matched control participants blood samples were collected in Liaoning province, China. Two polymorphisms (rs619586, rs4102217) in lncRNA MALAT1 were genotyped by KASP platform. Results: In a stratified analysis, we found that non-drinkers with GC genotype and the recessive model of rs4102217 had higher CAD risk (P=0.010, odds ratio (OR): 1.96, 95% confidence interval (CI) = 1.17-3.28; P=0.026, OR: 1.73, 95% CI = 1.07-2.79) and diabetes mellitus (DM) history group (P=0.010, OR: 4.07, 95% CI = 1.41-11.81; P=0.019, OR: 3.29, 95% CI = 1.22-8.88). In SNP-SNP interactions analysis between MALAT1 and CAD risk, we found rs4102217 had an increase in smokers (GG: OR: 2.04, 95% CI = 1.42-2.92; CC+GC: OR: 2.64, 95% CI = 1.64-4.26) and a decrease in drinkers (CC+GC: OR: 0.33, 95% CI = 0.20-0.55). Smokers with MALAT1 rs619586 AA genotype (OR: 2.20, 95% CI = 1.57-3.07) and GG+AG genotype (OR: 2.11, 95% CI = 1.17-3.81) had a higher risk of CAD. Moreover, drinkers with AA genotype (OR: 0.22, 95% CI = 0.10-0.48) and GG+AG genotype (OR: 0.38, 95% CI = 0.22-0.65) had a lower risk of CAD. According to the MDR software, MALAT1 rs4102217 polymorphism-smoking-drinking was the best interaction model, which has higher risk of CAD (Testing Bal.ACC. = 0.6979). Conclusion: Our study demonstrated that the GC genotype and the recessive model of rs4102217 potentially increased CAD risk in some specific group.

Dataset Information

Association Between Two Common Polymorphisms of Vitamin D Binding Protein and the Risk of Coronary Artery Disease: A Case-control Study.

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Association Between Two Common Polymorphisms of Vitamin D Binding Protein and the Risk of Coronary Artery Disease: A Case-control Study.

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