华法林相关基因SNPs在心脏瓣膜置换汉族患者中的分布调查

目的:探索心脏瓣膜置换的汉族患者中华法林相关基因SNPs的分布。方法:入选2012年至2013年上海市在中山医院行心脏瓣膜置换手术后,需长期服用华法林进行抗凝治疗的汉族患者110例,通过阅读文献筛选得到华法林相关基因及相应SNPs位点(CYP2C9 rs1799853 C/T、CYP2C9rs1057910 A/C、VKORC1 rs9923231 G/A、VKORC1 rs9934438 C/T、CYP4F2 rs2108622 C/T、GGCX rs12714145 A/G、EPHX1 rs1877724 C/T、EPHX1 rs2292566 A/G、EPHX1 rs4653436 A/G)。使用直接测序法检测SNPs,采用Hardy-Weinberg遗传平衡检验验证群体代表性。结果:CYP2C9基因rs1799853、rs1057910等位基因频率分别为0.45%、5.00%;VKORC1基因rs9923231、rs9934438等位基因频率均为91.36%;CYP4F2基因rs2108622等位基因频率为28.64%;GGCX基因rs12714145等位基因频率为33.18%;EPHX1基因rs1877724、rs2292566和rs4653436等位基因频率分别为30.00%、24.55%、26.36%。结论:探索华法林相关基因CYP2C9、VKORC1、CYP4F2、GGCX、EPHX1的9个SNPs的频率在行心脏瓣膜置换术的患者人群中的分布,对建立和实施华法林个体化治疗具有重要意义。

Distribution of warfarin-related gene polymorphisms in Chinese Han population receiving heart valve replacement

Objective： To investigate the distribution of warfarin-related gene polymorphisms in Han population receiving heart valve replacement. Methods： One hundred and ten Chinese Han patients receving warfarin anticoagulant therapy orally after valve replacement in Shanghai Zhongshan Hospital during 2012 and 2013were enrolled. Five warfarin-related genes-CYP2C9, VKORC1, CYP4F2, GGCX, EPHX1 with 9 SNPs including rs1799853 C/T, rs1057910 A/C, rs9923231 G/A, rs9934438 C/T, rs2108622 C/T, rs12714145 A/G, rs1877724 C/T, rs2292566 A/G, rs4653436 A/ G were investigated in the study. Direct sequencing was used to detect gene SNPs, and Hardy-Weinberg genetic equilibrium test was used to test population representativeness. Results： The allelic frequencies at CYP2C9 gene rs1799853 and rs1057910 loci were 0.45% and 5.00%; the allelic frequency at VKORC1 gene loci rs9923231 and rs9934438 were both 91.36%; the allelic frequency at CYP4F2 gene rs2108622 locus were 28.64%; the allelic frequencies at GGCX gene rs12714145 locus were 33.18%; the allelic mutation frequency at EPHX1 gene rs1877724, rs4653436 and rs2292566 loci were 30.00%, 24.55% and 26.36%, respectively. Conclusions： Investigation of distribution of warfarin-related gene polymorphisms is important for the individualization of warfarin therapy in patients receiving heart valve replacement.