SUMO4基因多态性与肾移植患者他克莫司浓度相关性的研究  

Associations of SUMO4 polymorphisms with tacrolimus concentrations in Chinese renal transplant recipients

作　　者：刘晓曼[1] 李嘉丽[1] 王洪阳[2] 傅茜[2] 李军[2] 刘澍[3] 孙萍萍[4] 王长希[2] 黄民[1] 

机构地区：[1]中山大学临床药理研究所,广东广州510080 [2]中山大学附属第一医院器官移植科,广东广州510080 [3]中山大学肿瘤防治中心药学部,广东广州510080 [4]中山大学附属第一医院药学部,广东广州510080

出　　处：《药学学报》2015年第2期180-184,共5页Acta Pharmaceutica Sinica

基　　金："十二五"国家科技重大专项资助项目(2012ZX09506001-004);国家自然科学基金资助项目(81102515;81320108027;81173131);广东省重点实验室建设项目(2011A060901014);广东省重大科技专项(2011A080300001;2012A080202013)

摘　　要：考察小泛素相关修饰蛋白4(SUMO4)的单核苷酸多态性(SNP)与肾移植患者术后早期他克莫司浓度之间的相关性。共纳入132例中国肾移植术后患者,采用Sequenom?Mass ARRAY system对SUMO4(rs237024,rs237025)进行基因分型,聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法对CYP3A5*3进行基因分型,并分析上述基因型对他克莫司浓度的影响。结果显示,SUMO4基因rs237024与rs237025位点间存在完全连锁不平衡(D'=1)。SUMO4 rs237024A-rs237025A型组(GA-GA型+AA-AA型)他克莫司剂量校正浓度显著高于GG-GG型组(P<0.05)。以CYP3A5*3基因型进行分层后,在表达型组中SUMO4 rs237024A-rs237025A型组(GA-GA型+AA-AA型)他克莫司剂量校正浓度显著高于GG-GG型组(P<0.05)。肾移植术后患者SUMO4rs237024、rs237025基因多态性与他克莫司浓度相关,该基因型检测将有助于指导他克莫司的临床个体化用药。The study aims to investigate the associations of SUMO4 polymorphisms with tacrolimus concentrations in Chinese renal transplant recipients. Blood samples and clinical data were collected from 132 renal transplant recipients with tacrolimus treatment. CYP3A5＊3 genotypes were detected by PCR-RFLP, and SUMO4（rs237024, rs237025） genotypes were detected by Sequenom Mass ARRAY system. SUMO4 rs237024 and rs237025 genotypes were in complete linkage disequilibrium（D＇ = 1）. The dose-adjusted concentration of tacrolimus in SUMO4 rs237024A-rs237025A（GA-GA ＋ AA-AA） carriers was considerably higher than that in GG-GG carriers（P 0.05）. After stratification by CYP3A5＊3 genotypes, SUMO4 rs237024A-rs237025 A carriers（GA-GA ＋ AA-AA） had a higher dose-adjusted tacrolimus concentration than that in GG carriers in CYP3A5 expresser（P 0.05）. The results illustrated that SUMO4 rs237024 and rs237025 polymorphisms were associated with tacrolimus concentrations, and the test of these genotypes may be useful for individualized medicine of tacrolimus.

关 键 词：他克莫司 SUMO4 基因多态性 肾移植 

分 类 号：R969[医药卫生—药理学]