title: Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis patients on methotrexate.
abstract: OBJECTIVE
  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 < or =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.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. ylee9@partners.org
authors.forename: Yvonne C
authors.initials: YC
authors.lastname: Lee
authors.forename: Jing
authors.initials: J
authors.lastname: Cui
authors.forename: Karen H
authors.initials: KH
authors.lastname: Costenbader
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Shadick
authors.forename: Michael E
authors.initials: ME
authors.lastname: Weinblatt
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Karlson
mesh_terms: D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D019877:Hydroxymethyl and Formyl Transferases / Q000235:genetics*; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000235:genetics*; D009709:Nucleotide Deaminases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D009097:Multienzyme Complexes; C113120:inosine monophosphate synthase; D002097:C-Reactive Protein; D019877:Hydroxymethyl and Formyl Transferases; D009709:Nucleotide Deaminases; D008727:Methotrexate