Fu Zhenyan, Zhu Qing, Ma Yitong, Huang Ding, Pan Shuo, Xie Xiang, Liu Fen, Cha Erdenbat
Department of Cardiovascular Medicine, First Affiliated Hospital of Xinjiang Medical University, Li Yu Shan South Road 137, Urumqi 830054, China.
Lipids Health Dis. 2014 Sep 2;13:143. doi: 10.1186/1476-511X-13-143.
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.
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.
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).
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.
细胞色素P450(CYP)2C9在血管内皮中表达,并将花生四烯酸代谢为具有生物活性的环氧二十碳三烯酸(EETs),其在调节心血管稳态中起关键作用。我们试图评估中国新疆汉族人群中人类CYP2C9基因与冠状动脉疾病(CAD)之间的关联。
使用实时荧光定量PCR仪对301例CAD患者和220例对照者进行人类CYP2C9基因的4个单核苷酸多态性(SNP)(rs4086116、rs2475376、rs1057910和rs1934967)基因分型。通过基于双倍型的病例对照研究对三组数据进行评估:总体、男性和女性。
对于女性,SNP2(rs2475376)的基因型、显性模型和等位基因分布在CAD患者和对照参与者之间存在显著差异(分别为p = 0.033、P = 0.010和p = 0.038)。在对女性协变量进行调整后,显性模型(CC与CT + TT)的显著差异仍然存在(OR:2.427,95%置信区间[CI]:1.305 - 4.510,p = 0.005)。CYP2C9基因中的单倍型(C - T - A - C)和双倍型(CTAC/CTAC)在CAD患者中低于对照者(分别为p* = 0.0016和p* = 0.036)。在女性中,CAD患者的单倍型(C - C - A - T)高于对照者(p* = 0.016)。
CYP2C9中rs2475376的CC基因型和C - C - A - T单倍型可能是女性CAD的风险遗传标记。rs2475376的T等位基因、单倍型(C - T - A - C)和双倍型(CTAC/CTAC)可能是中国汉族女性CAD的保护性遗传标记。