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同义突变 rs2515641 影响 CYP2E1 mRNA 和蛋白表达以及药物性肝损伤易感性。

Synonymous mutation rs2515641 affects CYP2E1 mRNA and protein expression and susceptibility to drug-induced liver injury.

机构信息

Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, PR China.

Center for Drug Evaluation, National Medical Products Administration, Beijing, PR China.

出版信息

Pharmacogenomics. 2020 May;21(7):459-470. doi: 10.2217/pgs-2019-0151. Epub 2020 Mar 9.

Abstract

To evaluate whether the synonymous mutant rs2515641 could affect cytochrome P450 2E1 () expression and the response to acetaminophen (APAP) or triptolide (TP) treatment. HepG2 cells were transfected with lentiviral vector containing either or . Some of these recombinant cells were then treated with APAP or TP. gene expression was detected by PCR and western blot. gene expression decreased significantly both in mRNA and protein level after rs2515641 mutation, indicating that this polymorphism can affect both transcription and translation. Furthermore, rs2515641 mutation dramatically changes the response of expression to APAP or TP treatment. Rs2515641 significantly changes expression and function, which would be expected to affect drug disposition and response.

摘要

为了评估同义突变 rs2515641 是否能影响细胞色素 P450 2E1 ()的表达以及对乙酰氨基酚 (APAP)或雷公藤红素 (TP)治疗的反应。将含有或的慢病毒载体转染 HepG2 细胞。然后,这些重组细胞中的一些用 APAP 或 TP 处理。通过 PCR 和 Western blot 检测基因表达。rs2515641 突变后,基因表达在 mRNA 和蛋白水平均显著降低,表明该多态性可影响转录和翻译。此外,rs2515641 突变显著改变了对 APAP 或 TP 处理的表达反应。rs2515641 显著改变了的表达和功能,这可能会影响药物处置和反应。

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