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Rheumatology Advance Access published online on February 4, 2009
Rheumatology, doi:10.1093/rheumatology/ken513
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis patients on methotrexate

Yvonne C. Lee1, Jing Cui1, Karen H. Costenbader1, Nancy A. Shadick1, Michael E. Weinblatt1 and Elizabeth W. Karlson1

1Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Correspondence to: Yvonne C. Lee, Division of Rheumatology, Immunology and Allergy, 75 Francis Street, PBB-B3, Boston, MA 02115, USA. E-mail: ylee9{at}partners.org


  Abstract

Objectives. We examined the association between candidate single nucleotide polymorphisms (SNPs) and disease activity in RA patients on MTX.

Methods. Our population was drawn from the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS), a prospective, observational cohort of RA patients. A total of 556 participants were genotyped using the Affymetrix 100K platform. Two hundred and sixty-two participants were on MTX therapy, including 120 on MTX monotherapy. The primary outcome was the disease activity score in 28 joints (DAS28-CRP). High disease activity was defined as DAS28-CRP >3.2. Low disease activity was defined as DAS28-CRP <=3.2. We studied three candidate alleles in the ATIC, ITPA and MTHFR genes for association with DAS28-CRP.

Results. Among participants on MTX monotherapy, those carrying the minor allele of ATIC SNP rs4673993 were more likely to have low disease activity (P = 0.01). None of the other SNPs was associated with disease activity. Among patients on any MTX (combination or monotherapy), the minor allele of ATIC rs4673993 was also associated with low disease activity (P = 0.04).

Conclusions. In this cross-sectional analysis, ATIC SNP rs4673993 was associated with low disease activity in patients on MTX. Further studies are needed to clarify the relationship between ATIC polymorphisms, disease activity and treatment response.

KEY WORDS: MTX, Adenosine, RA, Disease activity

Submitted 2 September 2008; Accepted 19 December 2008


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