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LncRNA MALAT1 gene polymorphisms in coronary artery disease: a case-control study in a Chinese population.

ABSTRACT: 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.

SUBMITTER: Hu W

PROVIDER: S-EPMC6422883 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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LncRNA MALAT1 gene polymorphisms in coronary artery disease: a case-control study in a Chinese population.

Hu Weina W Ding Hanxi H Ouyang An A Zhang Xiaohong X Xu Qian Q Han Yunan Y Zhang Xueying X Jin Yuanzhe Y

Bioscience reports 20190319 3

<b>Background:</b> 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 ...[more]

PMID: 30833365

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Project description:BackgroundMetastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been recognized as a major player in the pathogenesis of coronary artery disease (CAD). The aim of the study was to determine the association between polymorphisms of the MALAT1 gene and acute coronary syndrome (ACS) in a Chinese population in Xinjiang.MethodsIn the case-control study, we genotyped three nucleotide polymorphisms (rs3200401, rs4102217, rs600231) of the MALAT1 gene using SNPscanTM typing assays (1,053 controls and 929 ACS patients). Furthermore, we explored a predictive model using MALAT1 rs600231 and clinical variables to predict the risk of ACS. Finally, the relative expression of long noncoding RNA (lncRNA) MALAT1 was also measured in 92 ACS patients and 92 controls using quantitative real-time polymerase chain reaction (qRT-PCR).ResultsThe prevalence of the GG genotype of rs600231 in ACS group was higher than that in control group (15.7% vs. 14.7%, P=0.048). The dominant model differed (AG + GG vs. AA) and the G allele of rs600231 in ACS group was higher than that in control group (for dominant model: 66.2% vs. 60.9%, P=0.014; for allele: 41.0% vs. 37.8%, P=0.042). Multivariate logistic regression analysis and the predictive nomogram model showed that the dominant model of rs600231 remained an independent risk factor for ACS [odds ratio (OR) =1.32, 95% confidence interval (CI): 1.07-1.63, P=0.009]. The area under the receiver operating characteristic (ROC) curve (AUC) for the nomogram model for the prediction of ACS was 0.738 (95% CI: 0.716-0.761). In addition, in the AG and GG phenotypes, the relative expression of lncRNA MALAT1 was significantly higher in ACS patients than in controls with the same phenotypes (P<0.05). Among ACS group, compared to other genotype carriers, the relative expression level of MALAT1 in GG genotype carriers was higher (P<0.05).ConclusionsThe present study suggested that the AG and GG genotype of rs600231 in MALAT1 gene was independently associated with ACS, and could be a risk genetic marker of ACS in a Chinese population in Xinjiang.

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

LncRNA MALAT1 gene polymorphisms in coronary artery disease: a case-control study in a Chinese population.

Publications

LncRNA MALAT1 gene polymorphisms in coronary artery disease: a case-control study in a Chinese population.

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