尿苷二磷酸葡萄糖醛酸转移酶1A9基因多态性对麦考酚酸浓度的影响  

Influence of UGT1A9 genetic polymorphisms on mycophenolic acid exposure in Chinese kidney transplant recipients

作　　者：刘志宏[1] 沈兵[1] 龚华[1] 王忠[1] 王庆华[2] 祝捷[1] 范昱[1] 

机构地区：[1]上海市第一人民医院移植泌尿外科,200080 [2]南京军区福州总医院泌尿外科

出　　处：《中华器官移植杂志》2010年第10期607-610,共4页Chinese Journal of Organ Transplantation

基　　金：上海市器官移植中心课题（QY040101-2-19）

摘　　要：目的 了解中国汉族肾移植受者尿苷二磷酸葡萄糖醛酸转移酶1A9（UGT1A9）基因多态性对体内麦考酚酸（MPA）浓度的影响.方法 使用聚合酶链反应-连接酶检测反应（PCR-LDR）方法对196例汉族肾移植受者的UGT1A9编码基因进行单核苷酸基因多态性（SNP）检测,分别检测C-440T/T-331C、C-2152T、T-275A和T98C突变位点.移植后第28天,通过检测3个时间点（服用吗替麦考酚酯前、服药后0.5 h和2 h）的血浆MPA浓度来推算血浆MPA浓度的时间曲线下面积（MPA-AUC0-12）,对SNP和MPA-AUC0-12进行相关性分析.结果 受者的UGT1A9编码基因中,未发现C-2152T、T-275A、T98C突变;C-440T/T-331C突变频率为14.29%（28/196）.-440/-331位点CT/TC突变型受者的MPA-AUC0-12为（40.6±11.8）mg·h·L-1,野生纯合（CC/TT）基因型受者的MPA-AUC0-12为（37.6±14.2）mg·h·L-1,两者相比较,差异无统计学意义（P＞0.05）.结论 中国汉族肾移植受者的UGT1A9编码基因中,C-2152T、T-275A、T98C突变的发生频率较低,-440/-331位点突变多为杂合基因型.-440/-331位点的SNP与受者血浆MPA浓度没有明显的相关性.Objective To analyze the relationship between the genetic polymorphisms of uridinediphosphate glucuronosyltransferase 1A9 （UGT1A9） and mycophenolic acid （MPA）pharmacokinetics in Chinese kidney recipients.Methods Gene mutations （C-440T/T-331C,C-2152T,T-275A,T98C） were detected in 196 recipients by PCR-LDR.On the 28th day after transplantation,the plasma samples which were obtained at the time points of predose,0.5 h and 2 h after administration were measured by an immunoassay method （Emit Mycophenolic Acid Assay,Dade Behring）.MPA-AUC0-12 was calculated based on these three data.Correlation between single nucleotide polymorphisms （SNPs） and MPA pharmacokinetics was analyzed.Results C-2152T,T-275A and T98C genotypes of UGT1A9 were not found in 196 recipients.The frequency of C-440T/T-331C gene mutation was 14.29% （28/196）.The mean value of MPA-AUC0-12 was 40.6±11.8 wild genotype,respectively （P〉0.05）.Conclusion C-2152T,T-275A and T98C genotypes of UGT1A9 are scarce in Chinese kidney recipients.In this study,there is no distinct relationship between -440/-331 SNPs and MPA pharmacokinetics in Chinese allograft recipients.

关 键 词：尿苷二磷酸葡萄糖醛酸转移酶 多态性 单核苷酸 霉酚酸 药代动力学 

分 类 号：R686[医药卫生—骨科学]