title: Association of the ATIC 347 C/G polymorphism with responsiveness to and toxicity of methotrexate in rheumatoid arthritis: a meta-analysis.
abstract: This study investigated whether the 5-aminoimidazole-4-carboxamide ribonucleotide transformylase gene (ATIC) 347 C/G polymorphism can predict the response to or toxicity of methotrexate (MTX) in patients with rheumatoid arthritis (RA). We conducted a meta-analysis of studies on the association between ATIC 347 C/G polymorphism and non-responsiveness to or toxicity of MTX in RA patients, using PUBMED, EMBASE, and COCHRANE. Nine comparative studies from 6 articles including 1056 RA patients met our inclusion criteria. This final group of studies comprised 5 studies on response to MTX and 4 on toxicity of MTX in RA patients in relation to the ATIC 347 C/G polymorphism status. Meta-analysis showed association between the ATIC 347 GG + GC genotype and non-response to MTX therapy (OR = 1.572, 95 % CI 1.146-2.156, p = 0.005). Stratification by ethnicity indicated significant association between the ATIC 347 GG + GC genotype and non-response to MTX in Caucasians (OR = 1.884, 95 % CI 1.236-2.873, p = 0.003), but not in Asian patients. Similarly, associations were noted for the ATIC 347 C/G polymorphism through analysis using recessive and overdominant models. Meta-analysis revealed association between the ATIC 347 GG + GC genotype and MTX toxicity (OR = 1.454 95 % CI 1.034-2.044, p = 0.032). Stratification by ethnicity indicated significant association between the ATIC 347 GG + GC genotype and MTX toxicity in Caucasians (OR = 1.741, 95 % CI 1.080-2.806, p = 0.023), but not in Asian patients. The ATIC 347 C/G polymorphism may be associated with non-responsiveness to and or toxicity of MTX in Caucasian RA patients.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Korea University College of Medicine, Korea University Anam Hospital, 73, Inchon-ro, Seongbuk-gu, Seoul, Korea. lyhcgh@korea.ac.kr.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea.
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Bae
mesh_terms: D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D019877:Hydroxymethyl and Formyl Transferases / Q000235:genetics*; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D009097:Multienzyme Complexes / Q000235:genetics*; D009709:Nucleotide Deaminases / Q000235:genetics*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D009097:Multienzyme Complexes; C113120:inosine monophosphate synthase; D019877:Hydroxymethyl and Formyl Transferases; D009709:Nucleotide Deaminases; D008727:Methotrexate
keywords: ATIC; Meta-analysis; Polymorphism; Rheumatoid arthritis