新疆维吾尔族和哈萨克族健康人群CYP2C9和VKORC1基因多态性研究

Genetic Polymorphism of CYP2C9 and VKORC1 in Healthy Population of Uygur and Kazak Nationality in Xinjiang

目的:了解细胞色素P450(CYP)2C9、维生素K环氧化还原酶复合体1(VKORC1)基因单核苷酸多态性在新疆维吾尔族和哈萨克族健康人群中的频率分布及与其他不同民族之间的差异,为新疆维吾尔族和哈萨克族人群实施华法林个体化用药剂量提供理论依据。方法:采用BaiO华法林敏感性基因检测试剂盒的芯片检测技术对506位新疆维吾尔族和哈萨克族健康者的CYP2C9*2和CYP2C9*3位点以及VKORCI(-1639A/G和1173T/C)位点基因多态性进行检测,统计其等位基因和基因型频率,并与国外多个民族的这两个基因多态性分布进行比较。结果:506份样本中共检测到CYP2C9的3种等位基因CYP2C9*1、CYP2C9*2和CYP2C9*3,等位基因频率分别为89.6%、2.8%和7.6%;5种等位基因型分别为CYP2C9*1/*1,CYP2C9*1/*2,CYP2C9*1/*3,CYP2C9*2/*3和CYP2C9*3/*3。VKORC1-1639A/G检测出两种等位基因A和G,其频率分别为63.8%和36.2%;三种等位基因型AA(41.7%)、AG(44.3%)和GG(14%)的频率分别与1173T/C的TT、TC和CC型完全相同。结论:新疆维吾尔族和哈萨克族人群CYP2C9和VKORC1存在明显的基因多态性,其分布与中国汉族等亚洲人群以及欧美人群均存在较大差异。

Objective;To investigate the genetic polymorphism of cytochrome P450 2C9（CYP2C9）,and vitamin K epoxide reductase complex（VKORC1） in healthy people of Uygur and Kazak nationality in Xinjiang and compare with the frequencies in other ethnic populations to establish a theory platform for individualized warfarin therapeutic regimen.Method：CYP2C9 alleles＊2 and＊ 3,VKORC1（-1639A/G and 1173T/C） polymorphisms in 506 subjects were detected by microarray method.Frequencies of genotypes and alleles were calculated and compared with those in other populations.Result：CYP2C9 allele frequencies in 506 subjects were 89. 6%for CYP2C9＊1,2.8%for CYP2C9＊2 and 7.6%for CYP2C9＊3.Five genotypes were identified in the subjects,which were CYP2C9＊1/＊1,CYP2C9＊1/＊2,CYP2C9＊1/＊3,CYP2C9＊2/＊3 and CYP2C9＊3/＊3,respectively.Both of VKORC11639 A allele and VKORC1-1639 G allele were detected in the subjects,and the frequencies were 63.8%for A and 36.2%for G, and the frequency of VKORC1-1639 AA（41.7%）,AG（44.3%） and GG（14%） genotype was the same as that of 1173TT,TC and CC-lype.Conclusion;There is significant gene polymorphism of CYP2C9 and VKORC1 in Uygur and Kazak nationality,and the distribution of polymorphism is significantly different from Asian and America-European populations.