中文摘要：

目的：考察广东地区汉族人群中CYP2C9、CYP3A4、VKORC1和GGCX基因多态性分布。方法：入选2000至2008年广东省人民医院行瓣膜置换术长期口服华法林抗凝治疗的中国汉族患者970例,通过文献检索,选取与华法林药代学和药效学可能相关的CYP2C9、CYP3A4、VKORC1和GGCX 4种基因的12个单核苷酸多态性（singlenucleotide polymorphisms,SNPs）位点,分别为：rs12572351 G〉A、rs9332146 G〉A、rs4917639 G〉T、rs1057910 A〉C（CYP2C9＊3）、rs1934967 G〉T、rs1934968 G〉A、rs2242480 T〉C、rs2246709 G〉A、rs9923231 C〉T（VKORC1-1639G〉A）、rs2359612 G〉A（VKORC1＊2）、rs10871454 C〉T和rs699664 T〉C,比较系统地获得了中国汉族人群中12个SNPs突变频率的分布状况。SNPs的检测采用SNaPshot技术,群体代表性检验采用Hardy-Weinberg遗传平衡检验。结果：CYP2C9基因rs12572351 G〉A、rs9332146 G〉A、rs4917639 C〉A、rs1057910 A〉C（＊3）、rs1934967 G〉T和rs1934968 G〉A等位基因突变频率分别为32.53%、2.16%、8.25%、3.61%、19.18%和37.37%;CYP3A4基因rs2242480 T〉C和rs2246709 G〉A基因突变分别为29.07%和40.41%;VKORC1基因rs9923231 C〉T、rs2359612G〉A和rs10871454 C〉T SNPs位点等位基因突变频率分别为87.99%、87.94%和91.34%;GGCX基因rs699664T〉C基因突变为31.86%。结论：系统研究与华法林药代学和药效学相关的CYP2C9、CYP3A4、VKORC1和GGCX 4种基因12个SNPs的突变频率在中国汉族行瓣膜置换术患者人群中的分布,对于指导华法林个体化用药具有重要的临床意义。

英文摘要：

Objective：To investigate distribution of CYP2C9,CYP3A4,VKORC1 and GGCX gene polymorphisms in the Han population of Guangdong.Methods： The subjects included were 970 Chinese Han patients who received long-term warfarin anticoagulant therapy orally after valve replacement in Guangdong General Hospital between 2000 and 2008.By selecting and analyzing the 12 single nucleotide polymorphisms（SNPs） loci,rs12572351 GA,rs9332146 GA,rs4917639 GT,rs1057910 AC（CYP2C9＊3）,rs1934967 GT,rs1934968 GA,rs2242480 TC,rs2246709 GA,rs9923231 CT（VKORC1-1639 GA）,rs2359612 GA（VKORC1＊2）,rs10871454 CT,and rs699664 TC,in 4 genes including CYP2C9,CYP3A4,VKORC1 and GGCX that were possibly correlated with warfarin pharmacodynamics and pharmacokinetics through literature retrieval,the distribution of mutation frequencies of the 12 SNPs loci in Chinese Han population were obtained systematically.SNaPshot technique was used to detect gene SNPs,Hardy-Weinberg genetic equilibrium test was used to test population representativeness.Results： The allelic mutation frequency at CYP2C9 gene rs12572351 GA,rs9332146 GA,rs4917639 CA,rs1057910 AC（＊3）,rs1934967 GT and rs1934968 GA loci was 32.53%,2.16%,8.25%,3.61%,19.18% and 37.37%,respectively;the allelic mutation frequency at CYP3A4 gene rs2242480 TC and rs2246709 GA loci was 29.07% and 40.41%,respectively;the allelic mutation frequency at VKORC1 gene rs9923231 CT,rs2359612 GA and rs10871454 CT SNPs loci was 87.99%,87.94% and 91.34%,respectively;the allelic mutation frequency at GGCX gene rs699664 TC locus was 31.86%.Conclusion： It is of important clinical significance in individualized warfarin therapy to systematically study distribution of mutation frequencies at 12 polymorphisms loci in 4 genes including CYP2C9,CYP3A4,VKORC1 and GGCX related to warfarin pharmacodynamics and pharmacokinetics in the Chinese Han population receiving valve replacement.