中国人群华法林药效与细胞色素P4502C9基因多态性关系的系统评价和荟萃分析

System review and meta-analysis of effect in relationship of CYP 2C9 genetic polymorphisms with warfarin in Chinese patients

目的评价中国人群华法林(抗凝药)药效与CYP2C9基因多态性的关系。方法计算机检索相关中英文数据库,共纳入6篇回顾性研究(n=571)。用Re-view Manager4.2.9软件进行荟萃分析。结果突变型组较野生型纯合子组华法林平均日剂量低0.93mg[WMD合并=-0.93,95%CI(-1.31,-0.56),P<0.00001];同时,抗凝治疗的过量发生率也较高(P=0.0001)。纳入研究间比较具有异质性(P=0.02,I2=62.1%);敏感性分析表明,结果较为稳定可信。结论携带CYP2C9*2和/或*3突变者,华法林平均日剂量较低,出血风险较高。

Objective To evaluate the relationship of CYP2C9 genetic polymorphisms and warfarin in Chinese patients. Methods Databases were searched by computer. A meta-analysis was performed with The Cochrane Collaboration＇s Review Manager 4. 2. 9. Six literatures were included （n =571） 3 literatures in Chinese, 3 literatures in English. Results In comparison of the patient carried at least one variant allele （ CYP2C9 ＊ 2 or ＊3,n =64） and the wild-type（CYP2C9 ＊ 1/＊ 1 ,n =507） ： the mean daily warfarin dose was lower than that for the wild-type [ WMD： -0. 93, 95% CI （ -1.31, -0. 56）,P 〈0. 00001 ] ;only one study measured the bleeding risk： the over-anticoagulant incidence was higher than that for the wild-type [ P = 0. 0001 ]. There was heterogeneity of warfarin mean daily dose（ Heterogeneity test P = 0. 02, 12 = 62. 1% ）, but sensitivity analysis showed that the analysis results were stable and reliable. Conclusion Patient with cytochrome P450 2C9 ＊ 2 and/or ＊ 3 have lower mean daily warfarin dose and a greater bleeding risk.