甲氨蝶呤治疗类风湿关节炎疗效的预测性遗传生物标志物：一项系统评价

Predictive genetic biomarkers for the efficacy of methotrexate in rheumatoid arthritis: a systematic review.

作者信息

Eektimmerman Frank, Swen Jesse J, Madhar Moenira B, Allaart Cornelia F, Guchelaar Henk-Jan

机构信息

Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands.

Leiden Network for Personalised Therapeutics.

出版信息

Pharmacogenomics J. 2020 Apr;20(2):159-168. doi: 10.1038/s41397-019-0098-9. Epub 2019 Oct 17.

DOI:10.1038/s41397-019-0098-9

PMID:31624331

Abstract

Multiple pharmacogenetic studies investigated the effectiveness of methotrexate. However, due to the use of nonvalidated outcomes, lack of validation or conflicting results it remains unclear if genetic markers can help to predict response to MTX treatment. Therefore, a systematic review was performed. PubMed was searched for articles reporting potential pharmacogenetic biomarkers associated (p < 0.05) with MTX efficacy using the validated endpoints DAS(28), EULAR, or ACR response criteria. The PICO method was used for study selection, and PRISMA guidelines to prepare the report. Thirty-five studies met the inclusion criteria, providing 39 potential genetic biomarkers in 19 genes. After Bonferroni correction, six genetic biomarkers were associated with the efficacy of MTX: ATIC rs7563206; SLC19A1 rs1051266; DHFR rs836788; TYMS rs2244500, rs2847153, and rs3786362 in at least one study. Only SLC19A1 rs1051266 was replicated in an independent cohort and promising for predicting methotrexate efficacy.

摘要

多项药物遗传学研究调查了甲氨蝶呤的有效性。然而，由于使用了未经验证的结果、缺乏验证或结果相互矛盾，基因标记是否有助于预测对甲氨蝶呤治疗的反应仍不清楚。因此，进行了一项系统综述。在PubMed上搜索报告使用验证终点DAS(28)、欧洲抗风湿病联盟（EULAR）或美国风湿病学会（ACR）反应标准与甲氨蝶呤疗效相关（p < 0.05）的潜在药物遗传学生物标志物的文章。采用PICO方法进行研究选择，并遵循PRISMA指南编写报告。35项研究符合纳入标准，在19个基因中提供了39个潜在的遗传生物标志物。经过Bonferroni校正后，6个遗传生物标志物与甲氨蝶呤的疗效相关：ATIC rs7563206；SLC19A1 rs1051266；DHFR rs836788；TYMS rs2244500、rs2847153和rs3786362，至少在一项研究中是这样。只有SLC19A1 rs1051266在一个独立队列中得到了重复验证，有望用于预测甲氨蝶呤的疗效。