基因多态性对华法林个体化药量作用的临床分析

摘要

目的 探讨细胞色素氧化酶P450(CYP2C9)和环氧化物还原酶复合体(VKORC1)基因型与华法林个体化剂量的关系.方法 应用PCR-RFLP方法,检测临床长期口服华法林患者(362例)的VKORC1-1639及CYP2C9-1061A/C多态性,并按其基因型分组,分别比较VKORC1和 CYP2C9不同基因型间的平均华法林剂量.结果病例检测出VKORC1-1639 AA基因型273例(75.4%)、AC基因型81例(22.3%)及CC基因型8例(2.3%).CYP2C9基因检测AA型321例(88.7%)、AG基因型34例(9.5%)、GG型7例(1.8%).两组VKORC1和CYP2C9各基因型分布差异无统计学意义(P>0.05).VKORC1不同基因型间患者所需华法林平均剂量GA、GG组明显高于AA组(P0. 05 ). The mean warfarin dose differed significantly among the VKORC1 genotypes( P < 0.001 );the patients carrying VKORC1-1639 AA genotypes had a lower mean warfarin dose than those carrying AG genogype( P < 0. 05 ), and the mean warfarin dose of the patients with AG genotype was lower than those with GG genotype( P <0. 05 ). The carriers of CYP2C9-1061 C allel( AC + CC )had a lower warfarin dose than those with CYP2C9-1061 AA genotype( P <0. 05 ). Conclusion There might be an association between VKORC1-1639 G-A,CYP2C9-1061 A-C transformation and decreased warfarin dose,and the major genotype of VKORC1-1639( AA )might be the reason for the universally lower warfarin dosage used in Chinese Han population.