| 宋国贺 邓贵龙 王宇鹏 孙星 钟林 周崇治 沈兵 李培明 卢英豪 陈健 于洋 彭志海 王晓亮.体外研究UGT2B7 基因SNP rs28365062 对霉酚酸酯代谢的影响[J].,2015,15(30):5811-5815 |
| 体外研究UGT2B7 基因SNP rs28365062 对霉酚酸酯代谢的影响 |
| The Effect of SNP rs28365062 in UGT2B7 on MMF Metabolism |
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| DOI： |
| 中文关键词: 尿苷二磷酸葡萄糖醛酸转移酶 霉酚酸酯 副作用 |
| 英文关键词: UGT2B7 Mycophenolate mofetil Side-effect |
| 基金项目:国家自然科学基金项目（81270557，81110108010）；国家青年科学基金项目（81000188） |
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| 中文摘要: |
| 目的：体外研究尿苷二磷酸葡萄糖醛酸转移酶（UGT2B7）基因SNP rs28365062 对霉酚酸酯（MMF）代谢的影响，明确该位点
变异是否与MMF副作用具有潜在关系。方法：采用基因重组、定点突变技术构建UGT2B7 基因SNP rs28365062 不同等位基因过
表达载体，POLO3000 转染法将重组过表达载体转染HEK293 细胞，采用液相色谱- 质谱联用仪（LC/MS/MS）系统检测霉酚酸
（MPA）代谢产物--酰基化葡萄糖醛酸化物（AcMPAG）24 小时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
过表达载体pIRES2-EGFP-prom（A）和pIRES2-EGFP-prom（G）并转染至HEK293 细胞。LC/MS/MS 系统检测结果显示携带G等
位基因的突变型UGT2B7 代谢MMF产生AcMPAG 的能力降低，产物AcMPAG 24 小时的生成量仅为野生型的18.60 %（P<0.
001）。结论：UGT2B7 基因SNP rs28365062可显著影响MMF代谢产物AcMPAG的生成，可能是导致病人对MMF产生不同程度
副作用的因素之一。 |
| 英文摘要: |
| Objective:To investigate the effect of A/G mutation in SNP rs28365062 site of uridine diphosphate
glucuronosyltransferase（UGT2B7）on mycophenolate mofetil metabolism, clear the relationship between this mutation and side effect of
MMF.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 polo3000. LC/MS/MS
system was used to detect the yields of AcMPAG produced by different types of HEK293 cells in 24 hours, then, these cells transfected
by different alleles will be assessed by their enzyme activity.Results:The overexpression vectors pIRES2-EGFP-prom（A）and
pIRES2-EGFP-prom（G）were successfully constructed and transfected into HEK293 cells. The results analyzed by LC/MS/MS showed
that the cells containing mutant type of UGT2B7 gene with G allele produced less AcMPAG than that with A allele, generation amount in
24 hours of AcMPAG is 18.60%of UGT2B7 wild type, (P<0.001).Conclusion:UGT2B7 gene SNP rs28365062 can significantly affect
the production of AcMPAG，which may be one of the factors leading to patients have different degrees of side effects to MMF. |
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