UGT2B7基因SNP rs7439366影响霉酚酸酯代谢的体外研究  

Effect of SNP rs7439366 in UGT2B7 on MMF metabolism

作　　者：宋国贺 邓贵龙[1] 王宇鹏[1] 孙星[1] 钟林[1] 周崇治[1] 卢英豪[2] 张益[1] 陈健[1] 于洋[1] 彭志海[1] 王晓亮[1] 

机构地区：[1]上海交通大学附属第一人民医院普外科,200080 [2]贵阳医学院附属医院血液科,550004

出　　处：《医学研究杂志》2015年第11期22-25,共4页Journal of Medical Research

基　　金：国家自然科学基金资助项目(81270557;81110108010);国家自然科学基金青年科学基金资助项目(81000188)

摘　　要：目的体外研究尿苷二磷酸葡萄糖醛酸转移酶(UGT2B7)基因单核苷酸多态性(SNP)rs7439366对霉酚酸酯(MMF)代谢的影响。方法采用基因重组、定点突变技术构建UGT2B7基因rs7439366位点不同等位基因的过表达载体,Lipo2000转染法将重组载体转入HEK293细胞,采用LC/MS/MS系统检测霉酚酸(MPA)代谢产物7-O-葡醛酸苷(MPAG)24h的生成量来评估转染不同等位基因细胞的酶活性。结果成功构建p IRES2-EGFP-prom(T)和p IRES2-EGFP-prom(C)重组过表达载体并转染至HEK293细胞。LC/MS/MS系统检测结果显示携带C等位基因的突变型UGT2B7转化MPA的酶活性降低,24h产物MPAG的生成量为野生型的63.3%(P<0.001)。结论 UGT2B7基因SNP rs7439366可影响对MMF的代谢能力,是导致患者间MMF代谢差异的因素之一。Objective To investigate the effect of T/C mutation in rs7439366 site of uridine diphosphate glueuronosyhransferase on mycophenolate mofetil metabolism. Methods Wild and mutant type overexpression vectors containing UGT2B7 gene were constructed by recombinant gene technique and the strategy of site - directed mutagenesis. Then, target genes were transfected into HEK293 cells by lipo- fectamine and LC/MS/MS system was used to detect the yields of MPAG produced by different types of HEK293 cells. Results The overexpression vectors plRES2 - EGFP - prom （T） and pIRES2 - EGFP - prom （ C ） were successfully constructed and transfected into HEK293 cells. The cells containing UGT2B7 gene with rs7439366 - C alleles produced less MPAG than that with rs7439366 - T alleles （63.3% of UGT2BT wild type, P 〈 0. 001 ）. Conclusion The T→C variation of rs7439366 site in UGT2B7 gene can influence the me- tabolism of MMF.

关 键 词：尿苷二磷酸葡萄糖醛酸转移酶 霉酚酸酯 药物代谢 

分 类 号：R969.3[医药卫生—药理学]