CYP3A5＊3基因多态性与肾移植术后环孢素肝损伤的相关性  

Association of CYP3A5 ＊ 3 polymorphism with cyclosporine-induced liver injury in Chinese renal transplant recipients

作　　者：辛华雯[1] 刘慧明[1,2] 余爱荣[1] 吴笑春[1] 李罄[1] 

机构地区：[1]广州军区武汉总医院临床药理科,湖北武汉430070 [2]南方医科大学,广东广州510515

出　　处：《中国医院药学杂志》2011年第14期1199-1204,共6页Chinese Journal of Hospital Pharmacy

基　　金：湖北省自然科学基金计划资助项目(编号:2009CDB010)

摘　　要：目的:研究肾移植术后患者CYP3A5*3基因多态性对环孢素(CsA)所致肝损伤的影响。方法:采用PCR-RFLP(聚合酶链反应-限制性片段长度多态性)方法对359名肾移植患者进行CYP3A5*3基因型检测;荧光偏振免疫法检测肾移植患者CsA血浓度,根据肾移植患者发生肝脏损伤的情况分为CsA肝损伤组、其他原因肝损伤组和对照组。结果:在359名肾移植患者中,CYP3A5*3突变等位基因频率为73.5%。与对照组相比,CsA肝损伤组和其他原因肝损伤组的CYP3A5*3/*3分布频率明显增高(P<0.05或0.01),CsA肝损伤组的CYP3A5*3/*3分布频率亦明显高于其他原因肝损伤组(P<0.01)。肾移植术后1个月和3个月,CYP3A5*3/*3组和*1/*3组的CsA血谷浓度均明显高于*1/*1组(P<0.05)。术后7d、1个月、3个月、6个月,CsA肝损伤组的CsA谷浓度明显高于对照组(P<0.05或P<0.01)。Logistic回归模型显示,*3/*3基因型和术后6个月高CsA谷浓度是CsA肝损伤发生的危险因素。结论:CYP3A5*3基因多态性对肾移植患者CsA所致肝损伤有明显影响,携带*3突变基因的个体更易发生CsA所致肝损伤。OBJECTIVE To investigate the effects of CYP3A5 ＊ 3 genetic polymorphism on cyclosporine（CsA）-induced liver injury in Chinese renal transplant recipients. METHODS CYP3A5 ＊ 3 genotype was determined by PCR followed by restriction fragment length polymorphism （RFLP） analysis in a total of 359 renal transplant recipients receiving CsA. The whole blood CsA levels of renal transplant recipients were measured by fluorescence polarization immunoassay. All the subjects were divided into CsA-induced liver injury group, non-CsA-induced liver injury group and the control group according to the liver injury oc eurrence. RESULTS In this study of 359 renal transplant recipients, the frequency of the CYP3A5 ＊ 3 mutation allele was 73.5%. Compared with the control group, the distribution frequency of the CYP3A5 ＊ 3/＊ 3 was significantly increased in both CsA induced liver injury and non-CsA-induced liver injury group（P〈0. 05 or 0. 01）. Moreover, CsA-induced liver injury group showed obviously higher distribution frequency of CYP3A5 ＊ 3/＊ 3 than non-CsA-induced liver injury group（P〈0. 01 ）. One month later as well as three months after renal transplantation, the blood trough concentrations of CsA in CYP3A5 ＊ 3/＊ 3 and CYP3A5 ＊ 1/＊ 3 groups were significantly elevated than that in ＊ 1/＊ 1 group（P〈0. 05）. Seven days, one month, three months and six months after operation, CsA trough concentration of CsA-induced liver injury group appeared outstandingly higher than the control group （P〈0. 05 or P〈0. 01）. A logistic regression model showed that high CsA trough concentration of six months after operation and CYP3A5 ＊ 3/＊ 3 genotypes were the high risk factors of CsA-induced liver injury. CONCLUSION Genetic polymorphism of CYP3A5 ＊ 3 played an important role in CsA-induced liver injury after renal transplantation. The individuals carrying CYP3A5 ＊ 3 were prone to result in CsA-induced liver injury. 3

关 键 词：环孢素 肝损伤 肾移植 CYP3A5＊3 

分 类 号：R969.1[医药卫生—药理学]