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CYP19A1 polymorphisms associated with coronary artery disease and circulating sex hormone levels in a Chinese population.

ABSTRACT: The relationship between CYP19A1 genetic polymorphisms and coronary artery disease (CAD) remains unclear. Thus, the aim of the present study was to investigate the association of CYP19A1 genetic polymorphisms with CAD in Han and Uygur populations and to characterize the association between the levels of sex hormones and aromatase with single-nucleotide polymorphisms (SNPs) in CYP19A1 genes in Chinese women.There were significant differences in the genotype distributions of rs2236722 and rs4646 between CAD patients and control subjects in the Uygur population. The rs4646 was found to be associated with CAD in the dominant model (CC vs. CA + AA) and the additive model (CA vs. CC + AA) (both P ? 0.001). The difference remained statistically significant after multivariate adjustment (OR = 0.483, 95% CI: 0.338-0.690, P = 0.000; and OR = 1.844, 95% CI: 1.300-2.617, P = 0.001, respectively). In normal Uygur postmenopausal women, there were significant differences in the genotype distributions of rs4646 and the circulating hormone and aromatase levels between CAD patients and control subjects. The differences in estradiol and aromatase levels remained statistically significant after multivariate adjustment (OR = 0.889, 95% CI: 0.817-0.969, P = 0.007; and OR = 0.947, 95% CI: 0.936-0.957, P = 0.000, respectively). Additionally, there were differences in sex hormone levels between the different ethnicities among the Xinjiang Chinese population.Among a total of 1,064 Han individuals (614 men and 450 women) and 790 Uygur individuals (484 men and 306 women), 498 postmenopausal women (265 Han and 233 Uygur individuals) were selected. Four SNPs (rs2236722, rs2304463, rs4646, and rs4275794) were genotyped using the improved multiplex ligation detection reaction (iMLDR) technique. The estradiol and testosterone levels were determined using a radioimmunoassay based on GC-2016?. In addition, an enzyme-linked immunosorbent assay (ELISA) was performed to determine the serum P450 aromatase levels.The results of this study indicate that the rs2236722 and rs4646 of the CYP19A1 gene are associated with CAD and circulating sex hormone levels in the Xinjiang population of China.

SUBMITTER: Meng Y

PROVIDER: S-EPMC5722548 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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CYP19A1 polymorphisms associated with coronary artery disease and circulating sex hormone levels in a Chinese population.

Meng Yajie Y Adi Dilare D Wu Yun Y Wang Yongtao Y Abudoukelimu Mayila M Huang Ding D Ma Xiang X Liu Cheng C Wang Ting T Liu Fen F Chen Bangdang B Gai Mintao M Chen Xiaocui X Fu Zhenyan Z Ma Yitong Y

Oncotarget 20171007 57

<h4>Background</h4>The relationship between CYP19A1 genetic polymorphisms and coronary artery disease (CAD) remains unclear. Thus, the aim of the present study was to investigate the association of CYP19A1 genetic polymorphisms with CAD in Han and Uygur populations and to characterize the association between the levels of sex hormones and aromatase with single-nucleotide polymorphisms (SNPs) in CYP19A1 genes in Chinese women.<h4>Results</h4>There were significant differences in the genotype dist ...[more]

PMID: 29228596

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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.

Dataset Information

CYP19A1 polymorphisms associated with coronary artery disease and circulating sex hormone levels in a Chinese population.

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CYP19A1 polymorphisms associated with coronary artery disease and circulating sex hormone levels in a Chinese population.

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