肾移植病人中CYP3A4基因多态性对环孢素A代谢的影响  

Effect of CYP3A4 genetic polymorphism on cyclosporine A metabolism in Chinese renal transplant recipients

作　　者：储小曼[1] 曹文[1] 闵佩清[1] 张静[2] 孔诚[3] 周燕[1] 

机构地区：[1]南京军区南京总医院临床药理科,江苏南京210002 [2]第二军医大学药学院 [3]南京大学医学院

出　　处：《中国临床药理学杂志》2003年第6期421-425,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的用基因分析技术对CsA代谢酶CYP3A4进行基因分型,以阐述CYP3A4基因多态性对环孢素A代谢的影响及相互关系,从而预测血药浓度及安全性.方法用聚合酶链反应结合限制性片段长度多态性分析法分别建立了CYP3A的CYP3A4基因亚型3个新突变点(CYP3A4*4,*5,*6)的基因分型方法,并对中国肾移植人群进行基因分型,同时测定C sA及其代谢物浓度,以原形药与代谢物浓度的比值MR作为表型验证指标.结果CYP3A4*4,*5,*6等位基因在中国肾移植人群中的突变率为:2/133,3/197,3/200.野生型病人中肝肾功能正常和异常者测得MR均值分别为0.47±0.13和0.82±0.21.3种突变型病人MR均值为0.90±0.30.结论CYP3A4*4,*5,*6等位基因的存在有可能降低了药物代谢酶CYP3A4的活性,从而使环孢素A的代谢减慢.Objective To elucidate the effect of CYP3A4 genetic polymorphism on cyclosporine A(CsA) metabolism and disposition. Methods The samples from Chinese renal transplant recipients were analyzed.CYP3A4 genotype was determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Concentrations of CsA and metabolite were measured by fluorescence polarization immunoassay (FPIA) to obtain the metabolic ratio (MR) of CsA, which were used to further validate and evaluate the CYP3A4 genotype. Results The allele CYP3A4*4 was found in 2 of 133 subjects . The allele CYP3A4*5 was found in 3 of 197 subjects. And the allele CYP3A4*6 was 3 of 200 subjects. The MR value of subjects with variant allele CYP3A4*4,*5,*6 was 0.90±0.30 and higher than the MR value of subjects (wild type) with normal or non-normal liver and renal function, which were 0.47±0.13,0.82±0.21, respectively. Conclusion This pilot study suggests that the effect of CY3A4 genetic polymorphism may decrease the CYP3A4 activity that affected the metabolism of CsA.

关 键 词：肾移植 CYP3A4 基因多态性 环孢素A 药物代谢 基因分型 

分 类 号：R699.2[医药卫生—泌尿科学] R394[医药卫生—外科学]