中国现代医学杂志2017，Vol.27Issue(12)：9-14,6.DOI:10.3969/j.issn.1005-8982.2017.12.002
UGT1A10基因SNP rs10187694对吗替麦考酚酯代谢的影响
Effect of SNP rs10187694 of UGT1A10 gene on metabolism of Mycophenolate mofetil*
摘要
Abstract
Objective To study the effect of G/A mutation in SNP rs10187694 site of uridine diphosphate glucuronosyl transferase (UGT1A10) on Mycophenolate mofetil metabolism. Methods The recombinant overex-pression vectors of UGT1A10 gene were constructed by gene recombination technique and the strategy of site directed mutagenesis. Then, the recombinant plasmid was transfected into HEK293 cells by POLO3000 method. By detecting the yields of mycophenolic acid (MPA) metabolite 7-o-glucuronide (MPAG), the activity of enzyme in the HEK293 cells transfected with different alleles were evaluated. Results The overexperession vectors pIRES2-EGFP-prom (G) and pIRES2-EGFP-prom (A) were successfully constructed and transfected into HEK293 cells. The results analyzed by LC/MS/MS showed that the cells containing mutant type of UGT1A10 gene with A allele produced less MPAG than those with G allele, the concentration of MPAG produced by mutant type in 24 hours was (226.00 ± 14.57) nmol/L, however, the concentration in wild type was (269.00 ± 14.07) nmol/L. The generation amount of MPAG in mutant type was 84.00% of that in wild type in 24 hours (P< 0.05). Conclusions UGT1A10 gene SNP rs10187694 can significantly affect the production of MPAG, which may be one of the reasons causing the difference in Mycophenolate mofetil metabolism.关键词
尿苷二磷酸葡萄糖醛酸转移酶/霉酚酸酯/药物代谢Key words
UGT1A10/Mycophenolate mofetil/drug metabolism分类
医药卫生引用本文复制引用
肖超,王晓亮,孙红成,邓贵龙,宋国贺,王宇鹏,陈健,孙星,钟林,彭志海..UGT1A10基因SNP rs10187694对吗替麦考酚酯代谢的影响[J].中国现代医学杂志,2017,27(12):9-14,6.基金项目
国家自然科学基金(No:81270557,81110108010) （No:81270557,81110108010）
