Are gene polymorphisms related to adverse events of methotrexate in patients with rheumatoid arthritis? A retrospective cohort study based on an updated meta-analysis

• Published in: Therapeutic advances in chronic disease Vol. 11; p. 2040622320916026
• Main Authors: Huang, Jing, Fan, Huizhen, Qiu, Qi, Liu, Kunpeng, Lv, Shuang, Li, Jiang, Yang, Hui, Shu, Xiaoming, Xu, Yuan, Lu, Xiangchen, Lu, Cheng, Zhang, Yunnan, Xiao, Cheng
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 2020; SAGE PUBLICATIONS, INC; SAGE Publishing
• Subjects: Cohort analysis; Meta-analysis; Methotrexate; Original Research; Polymorphism; Rheumatoid arthritis; Side effects; methotrexate; polymorphism; adverse events; rheumatoid arthritis
• ISSN: 2040-6223; 2040-6231
• DOI: 10.1177/2040622320916026

Aims: We performed an updated meta-analysis to verify correlations between gene polymorphisms and adverse events in methotrexate (MTX)-treated rheumatoid arthritis (RA) patients. Then, we conducted a retrospective cohort study of Han Chinese in China. Methods: Relevant studies were collected from the PubMed database and the EMBASE database until December 2017. Pre-allele, dominant, recessive, codominant, and homozygotic models were applied. In addition, a retrospective cohort study enrolling 162 RA patients treated with MTX was conducted. Single nucleotide polymorphism (SNP) genotyping was analyzed by PCR and product sequencing. Results: A total of 39 studies were included in 20 meta-analyses; meta-analysis showed a significant association between MTX-related toxicity and 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C>T(rs1801133) polymorphism in East Asian RA patients, and significant associations were observed between MTX-related toxicity and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC) 347C>G (rs2372536), reduced folate carrier 1 (RFC-1) 80G>A (rs1051266), and adenosine triphosphate-binding cassette B1 (ABCB1) 3435C>T(rs1045642) polymorphisms in European RA patients but not in East Asian RA patients. Moreover, in our retrospective cohort study, ATIC 347C>G(rs2372536) and ABCB1 3435C>T(rs1045642) polymorphisms were not associated with MTX-related toxicity. However, a significant association was observed between MTX-related toxicity and RFC-1 80G>A (rs1051266) polymorphism in Chinese Han RA patients. Conclusion: Evidence-based results suggest that the MTHFR 677C>T(rs1801133), ATIC 347C>G(rs2372536), RFC-1 80G>A (rs1051266), ABCB1 3435C>T(rs1045642) polymorphisms are associated with MTX-related toxicity. Larger and more stringent study designs may provide more accurate findings for the effects of these SNPs on MTX-related toxicity, and larger sample-size studies of the Chinese Han population should be conducted for further validation.