细胞色素P4503A5~*3基因多态性与环孢素所致肝损伤相关性的评价

Analysis of the association between cytochrome P450 3A5~*3 genetic polymorphisms and liver injury induced by cyclosporine

目的系统评价细胞色素P450 3A5*3(CYP3A5*3)基因多态性与环孢素所致的肝损伤的相关性。方法系统检索Pub Med、MedLine、EMbase、Cochrane图书馆、维普数据库、中国知网和万方数据库,查找CYP3A5*3基因多态性与环孢素致患者肝损伤相关性的研究,检索时间自各数据库建库至2016年3月。试验组为环孢素致肝损伤患者,对照组为无肝损伤患者或其他原因致肝损伤患者。用Rev Man 5. 2. 0软件进行Meta分析。结果共纳入病例对照研究3篇(包括英文1篇和中文2篇),患者807名。患者的基因型分布均符合Hardy-Weinberg平衡定律。试验组和对照组CYP3A5*3AA型的分布率分别为21. 70%(87例/401例)和22. 36%(91例/407例),差异有统计学意义(P <0. 01)。试验组和对照组中携带等位基因A的分布率分别为21. 20%和32. 89%,携带等位基因G的分布率分别为78. 80%和67. 11%,差异均无统计学意义(均P> 0. 05)。结论 CYP3A5*3基因多态性与环孢素致患者肝损伤相关,其中携带CYP3A5*3AA基因型的患者服用环孢素所致肝损伤的发生率较低,而此发生率与等位基因A和G的分布无关。

Objective To systematically review the relationship between cytochrome P450 3A5* 3 (CYP3A5* 3) genetic polymorphism and liver injury induced by cyclosporine.Methods Retrieved from PubMed, EMbase,MedLine,Cochrane Library,VIP,CNKI and Wanfang databases. Study on the relationship between CYP3A5 * 3 genetic polymorphism and liver injury induced by cyclosporine were collected with time limit from establishment to March 2016.The treatment group was patients with liver injury induced cyclosporine,and the control group was patients without liver injury or with liver injury induced by other causes.Meta analysis software was RevMan 5.2.0.Results Three studies were included (English 1,Chinese 2) ,a total of 807 patients.The genotype distribution was consistent with the Weinberg-Hardy equilibrium aw. CYP3A5* 3AA gene type distribution of the treatment group and the control group were 21.70% (87 cases / 401 cases) and 22.36% (91 cases / 407 cases) with significant difference (P<0.01) .The allele distribution of A in the treatment group and the control group were 21.20% and 32.89%,and of G were 78.80% and 67.11%,without significant differences (allP> 0.05) .Conclusion The polymorphism of CYP3A5* 3 gene was related to the occurrence of liver injury induced by cyclosporine.The incidence of liver injury induced by cyclosporine was lower on AA genotype population,but the incidence was irrelevant with the distribution of the A and G alleles.