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

Yvonne C. Lee*, Jing Cui, Karen H. Costenbader, Nancy A. Shadick, Michael E. Weinblatt, Elizabeth W. Karlson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)613-617
Number of pages5
JournalRheumatology
Volume48
Issue number6
DOIs
StatePublished - 2009

Keywords

  • Adenosine
  • Disease activity
  • MTX
  • RA

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)

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