title: Effects of GSTM1 in rheumatoid arthritis; results from the Swedish EIRA study.
abstract: OBJECTIVE
  Glutathione-S-transferases (GSTs) play an important role in tobacco smoke detoxification, interestingly approximately 50% of individuals in most human populations lack the gene GSTM1 due to copy number variation (CNV). We aimed to investigate GSTM1 CNV in Rheumatoid Arthritis (RA) in relation to smoking and HLA-DRB1 shared epitope; the two best known risk factors for RA and in addition, to perform subanalyses in patients where relations between variations in GSTM1 and RA have previously been described.
  
  
  METHODS
  qPCR was performed using TaqMan Copy Number assays (Applied Biosystems) for 2426 incident RA cases and 1257 controls from the Swedish EIRA. Odds ratio (OR) together with 95% confidence intervals (CI) was calculated and used as a measure of the relative risk of developing RA.
  
  
  RESULTS
  No association between RA and GSTM1 CNV was observed when analyzing whole EIRA. However, ≥1 copy of GSTM1 appears to be a significant risk factor for autoantibody positive RA in non-smoking females ≥60 years (OR: 2.00 95% CI: 1.07-3.74), a population where such relationships have previously been described. Our data further suggest a protective effect of GSTM1 in ACPA-negative smoking men (OR: 0.56 95% CI: 0.35-0.90).
  
  
  CONCLUSIONS
  We assessed the exact number of GSTM1 gene copies in relation to development and severity of RA. Our data provide support for the notion that variations in copy numbers of GSTM1 may influence risk in certain subsets of RA, but do not support a role for GSTM1 CNV as a factor that more generally modifies the influence of smoking on RA.
authors: Department of Rheumatology, Karolinska Institutet, Stockholm, Sweden. emeli.lundstrom@ki.se
authors: Emeli
authors: E
authors: Lundström
authors: Toinette
authors: T
authors: Hartshorne
authors: Kelly
authors: K
authors: Li
authors: Staffan
authors: S
authors: Lindblad
authors: Marius C
authors: MC
authors: Wick
authors: Camilla
authors: C
authors: Bengtsson
authors: Lars
authors: L
authors: Alfredsson
authors: Lars
authors: L
authors: Klareskog
authors: Leonid
authors: L
authors: Padyukov
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics*; D018628:Gene Dosage; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D016133:Polymerase Chain Reaction; D013548:Sweden
chemical_list: D005982:Glutathione Transferase