亚洲人群VKORC1-1639基因多态性对华法林平均剂量影响的系统评价和Meta分析.docVIP

亚洲人群VKORC1 －1639 GA基因多态性对华法林 平均日剂量影响的系统评价和Meta-分析 郑少芳1,2，唐惠林1，胡永芳1( (北京大学，1. 第三医院 药剂科；2. 药学院 药事管理与临床药学系，北京 100191) 摘要 目的：评价亚洲人群VKORC1 -1639 GA 基因多态性对华法林平均日剂量的影响。 方法：计算机检索相关中英文数据库，用Revman 5.0.23软件进行Meta-分析。结果：纳入16篇研究（n=3,015），10篇英文，6篇中文。VKORC1-1639GA基因型发生频率在各人群间存在差异。与-1639AA组相比，-1639GG组、-1639GA组和-1639 GA+GG组患者平均日剂量分别高出104%[95% Confidence Interval （CI）：63%-146%]、52%[30%,73%]和75%[50%,101%]。敏感性分析以及人群间的亚组分析均表明，结果稳定、可信。结论：VKORC1-1639GA的基因多态性与华法林剂量个体间差异显著相关，对华法林药效的影响存在种族差异。 关键词 华法林；VKORC1；基因多态性；Meta-分析；亚洲人群 The influence of VKORC1 -1639GA genetic polymorphism on warfarin dose requirement in Asian populations: A systematic review and meta-analysis ZHENG Shao-fang1,2# , TANG Hui-lin1 , HU Yong-fang1# (1. Department of Pharmacy, Peking University Third Hospital；2. Department of Pharmacy Administration and Clinical Pharmacy; Peking University, Beijing 100191 China) Abstract: Objectives To quantify the influence of VKORC1 -1639GA genetic polymorphism on mean daily warfarin dose（MDWD） in Asian populations. Methods Related databases by computer, a meta-analysis was performed with the Review Manager 5.0.23. Results Sixteen studies (3,015 Asian patients) were included, 10 in English and 6 in Chinese. The frequencies of VKORC1-1639AA in Han Chinese and Japanese were higher than those in Uygur Chinese and Indian. Compared to the -1639AA genotype, patients with VKORC1 -1639GG, -1639GA and -1639 G carriers required 104% [95% Confidence Interval (CI):63%-146%], 52%[30%,73%] and 75%[50%,101%] higher MDWD, respectively. Sensitivity analysis and subgroup analysis demonstrated that the results of the meta-analysis were stable and reliable. Conclusion VKORC1-1639GA genotypes significantly associated with the inter-individual warfarin dosage requirement, and the impacts were interethnic variation. Key words: warfarin; VKORC1; genetic polymorphism; meta-analysis; Asian populations 目前，华法林是临床应用最广泛的口服抗凝药物，主要用于深静脉血栓形成、肺栓塞、房颤、心脏瓣膜置换术后等抗凝治疗。华法林个体差异大、治疗窗口窄，因而调整或确定华法林剂量，避免出血等不良反应发生，一直是临床上抗凝治疗管理的重