重庆地区人工机械瓣膜置换术后患者VKORCI-1639A/G遗传基因多态性与华法林剂量调整的研究

目的 探讨重庆地区人工机械瓣膜置换术后患者VKORCI-1639A/G基因多态性与华法林剂量和抗凝效果的关系.方法 采用PCR-RFLP技术对100例重庆地区汉族人工机械瓣膜置换术后抗凝治疗患者VKORC1-1639A/G多态性位点进行检测,计算其基因型和等位基因频率,同时记录患者服药期间的用药剂量.结果 100例重庆地区汉族人工机械瓣膜置换术后抗凝治疗患者中共筛选到2种等位基因:A和G.等位基因频率分别为92%和8%.,同时VKORC1-1639A/G基因多态性共检测到3种基因型,以AA基因型常见,基因型频率86%,其次为AG和GG型,分别为12%和2%.在达到抗凝指标(1.5～2.0)后,含有等基因G的患者需要的华法林维持剂量(5.27±0.55)mg]明显高于基因型为AA患者的华法林维持剂量(2.41±0.75)mg].100例重庆地区汉族人工机械瓣膜置换术后抗凝治疗患者VKORC1-1639A/G基冈多态性与相应的患者的口服剂量有相关.结论 VKORC1基因多态性与术后扰凝治疗患者华法林维持剂量有关系.

Effect of VKORC1-1639A/G genetic polymorphisms on warfarin dosage requirements and anticoagulation in patients with mechanical heart valve prostheses in Chongqing region

Objective To investigate the polymorphism of Vitamin K epoxide reductase complex subunit 1 (VKORC1-1639A/G) in patients with mechanical heart valve prostheses as well as the possible relationship be-tween the individual warfarin dosage requirements and this genetic polymorphism in Chinese patients in Chongqing region. Methods The polymorphism of VKORC1-1639A/G in 100 patients with mechanical heart valve prostheses operated in our department from September 1987 to October 2007 was detected by using PCR-RFLP and restriction enzyme digestion. The genotype and allelic frequencies were calculated and the individual warfarin dosage requirements were analyzed. Results In this group of patients VKORC1-1639A allele and VKORC1-1639G were detected, The frequency of A allele and G allele was 92% and 8% respectively. Three genotypes were detected too. AA was the most common genotype, with the frequency of 86%. The frequency of AG was 12% and the frequency of GG was less than 2% in these 100 patients. To achieve similar target INR range (1.5 to 2.5) , variant VKORC1-1639G homozygotes or heterozygotes required higher daily mean maintain doses (5.27±0.55 mg) than wild-type VKORC1-1639AA patients did (2.41±0.75 mg). VKORC1-1639A/ G polymorphism is associated with warfarin dose requirements in 100 patients with mechanical heart valve pros-theses receiving long-term therapy and showing stable control of anticoagulation in Chongqing region. Conclu-sion Polymorphism of VKORC1-1639A/G is dominant factor causing difference of individual warfarin dosage requirements ( P < 0. 01).