VKORC1-1639 G/A基因多态性与华法林应用剂量关系的研究

Relationship between VKORC1-1639G/A polymorphisms and warfarin dosage in Chinese

目的探讨维生素K环氧化物还原酶复合物1基因(VKORC1)-1639 G/A多态性对中国汉族人华法林应用剂量的影响。方法应用PCR-RFLP法检测129例长期口服华法林的患者和198例健康对照者VKORC1-1639 G/A多态性,比较VKORC1不同基因型间平均华法林剂量。结果病例组VKORC1-1639 AA、AG、GG基因型频率分别为74·4%(96/129)、23·3%(30/129)、2·3%(3/129),等位基因A和G频率分别为86%和14%。病例组与健康对照者VKORC1-1639 G/A多态性分布差异无统计学意义(P>0·05)。VKORC1-1639不同基因型患者所需华法林平均剂量差异有显著统计学意义(P<0·001),AA型剂量[(1·444±0·282)mg/INR]显著低于AG型[(1·629±0·258)mg/INR,P=0·002]和GG型患者[(2·031±0·087)mg/INR,P=0·017]。结论中国人华法林应用剂量偏低可能与VKORC1-1639 AA型占多数有关。

Objective To investigate the relationship between VKORCl-1639 G/A polymorphism and warfarin dosage in Chinese. Methods VKORCl-1639 G/A polymorphism was detected by PCR-RFLP technology in 129 warfarin-treated patients and 198 normal controls. The mean warfarin dosage was compared according to different VKORC1 genotypes. Results The frequencies of the VKORCl-1639 AA, AG, GG genotypes in the patient group were 74.4% （96/129） ,23.3% （30/129）and 2. 3% （3/129）, respectively; allele frequencies were 86% for VKORCl-1639 A and 14% for G. It showed no significant difference in genotype distribution of VKORCl-1639 between the patients and the normal controls. The mean warfarin dosage was significantly different among the VKORC1 genotypes （ P 〈 0. 001 ）. It was much lower in AA genotype （ 1. 444±0. 282 mg/INR） than in AG genotype （ 1. 629± 0. 258 mg/INR） （ P = 0.02） and GG genotype （2. 031 ± 0. 087 mg/INR,P = 0. 017 ）. Conclusions The high frequency of VKORCl-1639 AA genotype might be a cause of lower warfarin dosage in Chinese.