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Research Papers:

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

Yajie Meng, Dilare Adi, Yun Wu, Yongtao Wang, Mayila Abudoukelimu, Ding Huang, Xiang Ma, Cheng Liu, Ting Wang, Fen Liu, Bangdang Chen, Mintao Gai, Xiaocui Chen, Zhenyan Fu _ and Yitong Ma

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Oncotarget. 2017; 8:97101-97113. https://doi.org/10.18632/oncotarget.21626

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Abstract

Yajie Meng1,2,*, Dilare Adi1,2,*, Yun Wu1,2, Yongtao Wang1,2, Mayila Abudoukelimu1,2, Ding Huang1, Xiang Ma1,2, Cheng Liu1,2, Ting Wang1,2, Fen Liu1,2, Bangdang Chen1,2, Mintao Gai1,2, Xiaocui Chen1,2, Zhenyan Fu1,2 and Yitong Ma1,2

1Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, P.R. China

2Xinjiang Key Laboratory of Cardiovascular Disease Research, Urumqi, P.R. China

*These authors contributed equally to this work

Correspondence to:

Zhenyan Fu, email: [email protected]

Yitong Ma, email: [email protected]

Keywords: CYP19A1, coronary artery disease, sex hormone, polymorphisms

Abbreviations: CAD = Coronary artery disease; SNPs = Single-nucleotide polymorphisms; E2 = 17β-estradiol; T = Testosterone; A = Aromatase

Received: December 30, 2016     Accepted: September 20, 2017     Published: October 07, 2017

ABSTRACT

Background: 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.

Results: 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.

Materials and Methods: 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-2016γ. In addition, an enzyme-linked immunosorbent assay (ELISA) was performed to determine the serum P450 aromatase levels.

Conclusions: 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.


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