目的 系统评价我国成人肝移植患者中基因与药物治疗的研究现状,总结药物相关的基因,为肝移植受者的治疗提供循证医学参考。方法 计算机检索中国知网(CNKI)、万方数据库、中国生物医学文献数据库(CBM)、VIP数据库、PubMed、Web of Science、Embase、The Cochrane Library,同时查询纳入文献的相关参考文献,检索时间为建库至2022年4月,纳入涉及中国成人肝移植中基因与药物治疗的相关文献,分析相关基因与血药浓度、药物剂量、药动学、不良反应之间的关联性,对研究结果进行描述性分析。结果 共纳入60篇文献,发表时间为 2005~2022年,研究样本为18~373例,受者年龄分布在18~76岁。研究发现:CYP3A4、CYP3A5、MDR1等20余种基因与血药浓度/药物剂量相关;影响药动学的基因包括CYP3A5、MDR1、NR1I2、TLR4和TLR9;5种基因CYP2C8、CYP3A5、CYP3A4、SLC28A3和UGT1A8与不良反应相关。结论 中国成人肝移植中药物基因组学的研究发展迅猛,研究的基因呈现多样化,大部分基因位点的研究数量尚少,且结果存在差异,未来需要多中心、大样本、高质量研究来继续探索和验证相关基因与药物的确切作用。
Abstract
OBJECTIVE To review systematically the current studies of gene-based drug treatment in adult Chinese liver transplantation patients in order to provide evidence for the therapy of recipients. METHODS It was searched several databases including CNKI, WanFang Data, CBM, VIP, PubMed, Web of Science, Embase and The Cochrane Library from inception to April 2022. Literatures focusing on the association between related genes and drug plasma concentration, drug dosage, pharmacokinetics, and adverse drug reactions after liver transplantation in Chinese adult patients were included and descriptively analyzed. RESULTS A total of 60 articles published from 2005 to 2022 were included. Study samples varied between 18 and 373 cases, and recipients aged from 18 to 76 years. More than 20 genes, including CYP3A4, CYP3A5 and MDR1, were correlated with drug blood concentration and drug dosage. CYP3A5, MDR1, NR1I2, TLR4 and TLR9 genes could affect the pharmacokinetics. In addition, CYP2C8, CYP3A5, CYP3A4, SLC28A3 and UGT1A8 were associated with adverse drug reactions. CONCLUSION Pharmacogenomic research in adult Chinese liver transplantation patients develop rapidly, and the related genes are diversified. However, the number of studies on most genes is still small and the results are varied. Multi-center, large-sample, high-quality studies are still needed in the future to further explore and validate the exact role between genes and drugs.
关键词
肝移植 /
药物基因组学 /
循证评价
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Key words
liver transplantation /
pharmacogenomics /
systematical review
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参考文献
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脚注
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基金
北京医卫健康公益基金会医学科学研究基金项目资助(YWJKJJHKYJJ-B21003FN);白求恩·医学科学研究基金项目资助(TA201933)
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