Abstract
BackgroundThe 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.ResultsThere 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 MethodsAmong 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.ConclusionsThe 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.
Highlights
Coronary artery disease (CAD) is a complex multifactorial cardiovascular disease that is influenced by both genetics and environmental risk factors
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)
The results of this study indicate that the rs2236722 and rs4646 of the CYP19A1 gene are associated with coronary artery disease (CAD) and circulating sex hormone levels in the Xinjiang population of China
Summary
Coronary artery disease (CAD) is a complex multifactorial cardiovascular disease that is influenced by both genetics and environmental risk factors. Many studies have examined whether genetic variations in CYP19A1 are associated with cardiovascular diseases [6,7,8]. Despite these efforts, the potential molecular mechanisms linking estrogen-related genes with CAD risk remain incompletely understood. 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
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