Meng Yajie, Adi Dilare, Wu Yun, Wang Yongtao, Abudoukelimu Mayila, Huang Ding, Ma Xiang, Liu Cheng, Wang Ting, Liu Fen, Chen Bangdang, Gai Mintao, Chen Xiaocui, Fu Zhenyan, Ma Yitong
Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, P.R. China.
Xinjiang Key Laboratory of Cardiovascular Disease Research, Urumqi, P.R. China.
Oncotarget. 2017 Oct 7;8(57):97101-97113. doi: 10.18632/oncotarget.21626. eCollection 2017 Nov 14.
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 ≤ 0.001). The difference remained statistically significant after multivariate adjustment (OR = 0.483, 95% CI: 0.338-0.690, = 0.000; and OR = 1.844, 95% CI: 1.300-2.617, = 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, = 0.007; and OR = 0.947, 95% CI: 0.936-0.957, = 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-2016γ. 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.
细胞色素P450 19A1（CYP19A1）基因多态性与冠状动脉疾病（CAD）之间的关系仍不清楚。因此，本研究旨在探讨CYP19A1基因多态性与汉族和维吾尔族人群CAD的相关性，并阐明中国女性中CYP19A1基因单核苷酸多态性（SNP）与性激素及芳香化酶水平之间的关联。
维吾尔族人群中，CAD患者与对照者之间rs2236722和rs4646的基因型分布存在显著差异。rs4646在显性模型（CC与CA + AA）和加性模型（CA与CC + AA）中均与CAD相关（均P≤0.001）。多变量调整后差异仍具有统计学意义（OR = 0.483，95%CI：0.338 - 0.690，P = 0.000；OR = 1.844，95%CI：1.300 - 2.617，P = 0.001）。在正常维吾尔族绝经后女性中，CAD患者与对照者之间rs4646的基因型分布以及循环激素和芳香化酶水平存在显著差异。多变量调整后，雌二醇和芳香化酶水平的差异仍具有统计学意义（OR = 0.889，95%CI：0.817 - 0.969，P = 0.007；OR = 0.947，95%CI：0.936 - 0.957，P = 0.000）。此外，新疆汉族人群中不同民族之间的性激素水平存在差异。
在总共1064名汉族个体（614名男性和450名女性）和790名维吾尔族个体（484名男性和306名女性）中，选取了498名绝经后女性（265名汉族和233名维吾尔族个体）。使用改进的多重连接检测反应（iMLDR）技术对4个SNP（rs2236722、rs2304463、rs4646和rs4275794）进行基因分型。采用基于GC - 2016γ的放射免疫分析法测定雌二醇和睾酮水平。此外，进行酶联免疫吸附测定（ELISA）以测定血清P450芳香化酶水平。
本研究结果表明，CYP19A1基因的rs2236722和rs4646与中国新疆人群的CAD及循环性激素水平相关。
