title: Polymorphisms and Pharmacogenomics for the Clinical Efficacy of Methotrexate in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-analysis.
abstract: Methotrexate (MTX) is widely used and considered a first-line disease modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). Many of the relevant genes have been investigated to estimate the association between gene polymorphisms and MTX effectiveness in RA patients, although inconsistent results have been reported. A systematic review and meta-analysis were performed to identify genetic variants associated with MTX efficacy. A total of 30 publications that included 34 genes and 125 SNPs associated with the transporters, enzymes, and metabolites of MTX or the progression of RA were included in the systematic review (SR), and 21 studies were included in 9 meta-analyses. Associations between MTX response in RA patients in MTHFR 1298A > C (rs1801131), ATIC 347C > G (rs2372536), RFC-1 80G > A (rs1051266), SLC19A1 A > G (rs2838956) and SLC19A1 G > A (rs7499) genetic polymorphisms were found, but not observed between the MTHFR 677C > T (rs1801133), TYMS 28 bp VNTR (rs34743033), MTRR 66A > G (rs1801394), and ABCB1 3435C > T (rs1045642). However, for the polymorphisms not being associated following meta-analysis could still be associated if larger cohorts were used, and studies of other polymorphisms are necessary in large cohorts and a rigorous way, which may provide more accurate results for the effect of the gene polymorphisms on the MTX response.
authors.affiliation: Institute of Clinical Pharmacology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Qiu
authors.affiliation: Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing 100029, China.|Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Rheumatology, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Shu
authors.affiliation: Department of Gastroenterology, People's Hospital of Yichun, Jiangxi Yichun 336000, China.
authors.forename: Huizheng
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.|Molecular Medicine Lab and Chieng Genomics Center, Vancouver Coastal Health Research Institute, Vancouver, Canada.
authors.forename: Youwen
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Xiao
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use*; D000071185:Pharmacogenomic Testing; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D008727:Methotrexate