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Association of the ATIC 347 C/G polymorphism with responsiveness to and toxicity of methotrexate in rheumatoid arthritis: a meta-analysis

  • Genes and Disease
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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.

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Acknowledgments

This study was supported in part by a grant of the Korea Healthcare technology R&D Project, Ministry for Health and Welfare, Republic of Korea (HI15C2958).

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Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Korea University College of Medicine, Korea University Anam Hospital, 73, Inchon-ro, Seongbuk-gu, Seoul, Korea

    Young Ho Lee

  2. Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea

    Sang-Cheol Bae

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  1. Young Ho Lee
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Correspondence to Young Ho Lee.

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Lee, Y.H., Bae, SC. Association of the ATIC 347 C/G polymorphism with responsiveness to and toxicity of methotrexate in rheumatoid arthritis: a meta-analysis. Rheumatol Int 36, 1591–1599 (2016). https://doi.org/10.1007/s00296-016-3523-2

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