Liu Yuan, Zhong Shi-long, Yang Min, Tan Hong-hong, Fei Hong-wen, Chen Ji-yan, Yu Xi-yong, Lin Shu-guang
Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2011 Dec 18;43(6):798-803.
To investigate distribution of CYP2C9, CYP3A4, VKORC1 and GGCX gene polymorphisms in the Han population of Guangdong.
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 G>A, rs9332146 G>A, rs4917639 G>T, rs1057910 A>C (CYP2C93), rs1934967 G>T, rs1934968 G>A, rs2242480 T>C, rs2246709 G>A, rs9923231 C>T (VKORC1-1639 G>A), rs2359612 G>A (VKORC12), rs10871454 C>T, and rs699664 T>C, 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.
The allelic mutation frequency at CYP2C9 gene rs12572351 G>A, rs9332146 G>A, rs4917639 C>A, rs1057910 A>C (*3), rs1934967 G>T and rs1934968 G>A loci was 32.53%, 2.16%, 8.25%, 3.61%, 19.18% and 37.37%, respectively; the allelic mutation frequency at CYP3A4 gene rs2242480 T>C and rs2246709 G>A loci was 29.07% and 40.41%, respectively; the allelic mutation frequency at VKORC1 gene rs9923231 C>T, rs2359612 G>A and rs10871454 C>T SNPs loci was 87.99%, 87.94% and 91.34%, respectively; the allelic mutation frequency at GGCX gene rs699664 T>C locus was 31.86%.
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.
研究广东汉族人群中CYP2C9、CYP3A4、VKORC1和GGCX基因多态性的分布情况。
研究对象为2000年至2008年在广东省人民医院接受瓣膜置换术后长期口服华法林抗凝治疗的970例中国汉族患者。通过文献检索选取并分析CYP2C9、CYP3A4、VKORC1和GGCX这4个可能与华法林药效学和药代动力学相关基因中的12个单核苷酸多态性（SNP）位点，即rs12572351 G>A、rs9332146 G>A、rs4917639 G>T、rs1057910 A>C（CYP2C93）、rs1934967 G>T、rs1934968 G>A、rs2242480 T>C、rs2246709 G>A、rs9923231 C>T（VKORC1-1639 G>A）、rs2359612 G>A（VKORC12）、rs10871454 C>T和rs699664 T>C，系统获得这12个SNP位点在中国汉族人群中的突变频率分布情况。采用SNaPshot技术检测基因SNP，用Hardy-Weinberg遗传平衡检验来检验群体代表性。
CYP2C9基因rs12572351 G>A、rs9332146 G>A、rs4917639 C>A、rs1057910 A>C（*3）、rs1934967 G>T和rs1934968 G>A位点的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位点的等位基因突变频率分别为29.07%和40.41%；VKORC1基因rs9923231 C>T、rs2359612 G>A和rs10871454 C>T SNP位点的等位基因突变频率分别为87.99%、87.94%和91.34%；GGCX基因rs699664 T>C位点的等位基因突变频率为31.86%。
系统研究接受瓣膜置换的中国汉族人群中与华法林药效学和药代动力学相关的CYP2C9、CYP3A4、VKORC1和GGCX这4个基因中12个多态性位点的突变频率分布情况，对华法林个体化治疗具有重要的临床意义。
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