甲氨蝶呤治疗银屑病的药物基因组学文献分析

Pharmacogenomic Analysis of Methotrexate in the Treatment of Psoriasis

目的探讨甲氨蝶呤(MTX)治疗银屑病安全性及有效性的药物基因组学研究进展,为其个体化应用及相关研究提供参考。方法采用主题字段关键词“银屑病”“甲氨蝶呤”或“MTX”“基因”或“药物基因组学”与“Methotrexate”“Psoriasis”“Pharmacogenomics”,在中国知网、万方数据、维普网、Web of Science TM核心数据库中组合查询2000年1月—2019年12月发表的相关文献,对其发表信息、甲氨蝶呤药物基因组学等内容进行归纳。结果共收录有效文献39篇,其中外文文献31篇、中文文献8篇,以高校科研院所发表为主。以英国、美国、加拿大和中国学者的发表量较高,英国、爱尔兰、加拿大学者发表文献的总被引频次较高,其中排序前10位的文献中,4篇刊登于British Journal of Dermatology,以Warren RB等英国学者为主。MTX转运体编码基因(SLC19A1、ABCC1、ABCG2),代谢酶编码基因(MTHFR、DHFR),药物靶点(TYMS、ATIC、ADORA2a)等基因多态性可能改变甲氨蝶呤的药动学和药效学特征,从而影响甲氨蝶呤的安全性和有效性,可一定程度解释甲氨蝶呤治疗银屑病的个体差异。结论目前国外较国内研究的甲氨蝶呤药物基因组学内容更为全面、深入,由于现有文献以外文文献居多,基于种族基因图谱的差异,其结论不一定适用于我国人群,故我国学者有必要进行更多的相关研究,以确定甲氨蝶呤药物基因多态性对银屑病患者应用甲氨蝶呤治疗安全性及有效性的影响。

Objective To review the pharmacogenomic research of methotrexate(MTX)in the treatment of psoriasis,and to provide references for personalized pharmaceutical services and medical research.Methods The related literatures were retrieved from the web of scienceTM core database,Wanfang,and VIP database with the subject retrieval method,scoping from 2000 to 2019.The indicators were analyzed,such as the year of publication,literature types,countries and regions,institutions and authors,cited situation,research direction,etc.Results Area total of 39 foreign literatures and 8 domestic researches on the effectiveness and toxicity of MTX and pharmacogenomics were concluded in this analysis.Most publications were from the UK,the United States,Canada,and China;and the publications with the higher citation distributed in the UK,Ireland and the United States.Among the top 10 cited literatures,4 were published in British Journal of Psychiatry,and most of them were British scholars,such as Warren RB.in the UK.MTX transporter coding genes(SLC19A1,ABCC1,ABCG2),metabolizing enzyme coding genes(MTHFR,DHFR),drug targets(TYMS,ATIC,ADORA2a)and other gene polymorphisms may change the pharmacokinetic and pharmacodynamic characteristics of MTX,thus affecting the safety and effectiveness of MTX,which may explain the individual differences in the treatment of psoriasis by MTX to a certain extent.Conclusion The research on pharmacogenomics,efficacy and toxicity of MTX in the treatment of psoriasis has been carried out all over the world.Chinese academic researchers should pay more attention to these fields because of the difference between the gene backgrounds of different races and nationalities to ensure the safety and efficacy of MTX in the treatment of psoriasis.