Diplotypes of CYP2C9 gene is associated with coronary artery disease in the Xinjiang Han population for women in China

Abstract

Background

Cytochrome P450 (CYP) 2C9 is expressed in the vascular endothelium and metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids (EETs), which have the crucial role in the modulation of cardiovascular homeostasis. We sought to assess the association between the human CYP2C9 gene and coronary artery disease (CAD) in Xinjiang Han Population of China.

Methods

301 CAD patients and 220 control subjects were genotyped for 4 single-nucleotide polymorphisms (SNPs) of the human CYP2C9 gene (rs4086116, rs2475376, rs1057910, and rs1934967) by a Real-Time PCR instrument. The datas were assessed for 3 groups: total, men, and women via diplotype-based case–control study.

Results

For women, the distribution of genotypes, dominant model and alleles of SNP2 (rs2475376) showed significant difference between the CAD patients and control participants (p = 0.033, P = 0.010 and p = 0.038, respectively). The significant difference of the dominant model (CC vs CT + TT) was retained after adjustment for covariates in women (OR: 2.427, 95% confidence interval [CI]: 1.305-4.510, p = 0.005). The haplotype (C-T-A-C) and the diplotypes (CTAC/CTAC) in CYP2C9 gene were lower in CAD patients than in control subjects (p* = 0.0016, and p* = 0.036 respectively). The haplotype (C-C-A-T) was higher in the CAD patients than in the control subjects in women (p* = 0.016).

Conclusions

CC genotype of rs2475376 and C-C-A-T haplotype in CYP2C9 may be a risk genetic marker of CAD in women. T allele of rs2475376, the haplotype (C-T-A-C) and the diplotype (CTAC/CTAC) could be protective genetic markers of CAD for women in Han population of China.