RESEARCH - Investigation of candidate polymorphisms and disease activity in RA patients on MTX

February 18, 2009

Rheumatology Advance Access published online on February 4, 2009

Rheumatology, doi:10.1093/rheumatology/ken513

Investigation of candidate polymorphisms and disease activity in

rheumatoid arthritis patients on methotrexate

C. Lee1, Jing Cui1, H. Costenbader1, A. Shadick1,

E. Weinblatt1 and W. Karlson1

1Division of Rheumatology, Immunology and Allergy, Brigham and Women's

Hospital and Harvard Medical School, Boston, MA, USA.

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.

Not an MD

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