【摘要】 目的研究湖北地区汉族人细胞色素P450酶2C9(CYP2C9)基因和维生素K环氧化物还原酶复合体1(VKORC1)基因多态性分布特点及其对华法林稳态剂量的影响。方法收集2012年3—8月湖北地区汉族临床使用华法林的患者108例作为华法林组,选择同期健康受试者85名为对照组。采用聚合酶链反应-限制性内切酶片段长度多态性(PCR-RFLP)技术检测CYP2C9和VKORC1基因型,并比较不同基因型华法林稳态剂量。结果两组基因型频率和等位基因频率分布比较差异无统计学意义(P>0.05)。华法林组中CYP2C9基因*1/*3型较*1/*1型华法林稳态剂量小,VKORC1基因AA型较GA型华法林稳态剂量小(P<0.05,P<0.01)。除了检测的3个多态位点,还发现了50多个变异位点。结论在湖北地区汉族人群中,存在CYP2C9和VKORC1基因多态性,且不同基因型患者间华法林稳态剂量存在差异,华法林基因相关变异位点需要进一步证实。更多还原

【Abstract】 Objective To investigate characteristics of polymorphism distribution of cytochrome P450 2C9( CYP2C9) and vitamin K epoxide reductase complex 1( VKORC1) genotypes and the influence on Warfarin dose in Han population of Hubei Province. Methods A total of 108 patients of Han Nationality taking Warfarin in Hubei Province from March to August of 2012 were chosen as Warfarin group,and 85 healthy volunteers at the same period were chosen as control group. Genotypes of CYP2C9 and VKORC1 were detected with polymerase chain reaction-restriction fragment length polymorphism( PCR-RFLP) technique in the two groups,and stable Warfarin doses of different genotypes were also compared. Results There were no significant differences in distributions of genotype frequency and allele frequency( P > 0. 05). In Warfarin group,stable Warfarin dose of patients with CYP2C9* 1 /* 3 type was significantly smaller than that of patients with CYP2C9* 1 / * 1,and stable Warfarin dose of patients with VKORC1 AA type were significantly smaller than that of patients with VKORC1 GA type( P < 0. 05,P < 0. 01). More than fifty variant sites were found in addition to the 3 detected polymorphic sites. Conclusion There are polymorphisms of CYP2C9 and VKORC1 in Han population of Hubei Province,and there are significant differences in stable Warfarin dosage in patients with different genotypes,but relevant Warfarin variant sites need to be further studied.更多还原