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Association of the ATG9B gene polymorphisms with coronary artery disease susceptibility: A case-control study.

ABSTRACT: Introduction: Endothelial nitric oxide synthase (eNOS), the main regulator of cardiac cell functioning, is regulated post-transcriptionally by autophagy-related 9B (ATG9B) gene. The proper function of the heart is partly determined by the intact interaction of these molecules. The present study aimed to investigate the effects of ATG9B rs2373929 and rs7830 gene polymorphisms on the predisposition to coronary artery disease (CAD). Methods: In this hospital-based case-control study, 150 patients with CAD compared with 150 healthy subjects for the genotype distributions of rs2373929 and rs7830 polymorphisms using T-ARMS PCR and ARMS PCR, respectively. Results: Considering rs2373929 polymorphism, increased risk of CAD observed in the presence of TT genotype (OR: 3.65; 95% CI: 1.77-7.53; P < 0.001) and also in the recessive model for T allele (OR: 3.41; 95% CI: 1.76- 6.60; P < 0.001). The frequency of the T allele was higher in cases compared to controls (OR: 1.71; 95% CI: 1.24-2.28; P = 0.001). The genotype and allele frequencies of the rs7830 polymorphism did not differ between the two study groups. Conclusion: The ATG9B gene rs2373929 polymorphism might involve in the pathogenesis of the CAD and can be considered as a screening molecular marker in the subjects prone to CAD.

SUBMITTER: Mehrabi Pour M

PROVIDER: S-EPMC6669433 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Association of the ATG9B gene polymorphisms with coronary artery disease susceptibility: A case-control study.

Mehrabi Pour Mahsa M Nasiri Mahboobeh M Kamfiroozie Hajar H Zibaeenezhad Mohammad Javad MJ

Journal of cardiovascular and thoracic research 20190625 2

Introduction: Endothelial nitric oxide synthase (eNOS), the main regulator of cardiac cell functioning, is regulated post-transcriptionally by autophagy-related 9B (ATG9B) gene. The proper function of the heart is partly determined by the intact interaction of these molecules. The present study aimed to investigate the effects of ATG9B rs2373929 and rs7830 gene polymorphisms on the predisposition to coronary artery disease (CAD). Methods: In this hospital-based ...[more]

PMID: 31384404

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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.

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.

Dataset Information

Association of the ATG9B gene polymorphisms with coronary artery disease susceptibility: A case-control study.

Publications

Association of the <i>ATG9B</i> gene polymorphisms with coronary artery disease susceptibility: A case-control study.

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