title: Smoking and disease severity in rheumatoid arthritis: association with polymorphism at the glutathione S-transferase M1 locus.
abstract: OBJECTIVE
  To determine whether the relationship between smoking and disease severity in women with rheumatoid arthritis (RA) is associated with polymorphism at the glutathione S-transferase (GST) M1 locus.
  
  
  METHODS
  Genotyping for GSTM1 was carried out using polymerase chain reaction methodology on 164 women with established RA. Smoking history was obtained on each patient. Radiographic damage was measured by the Larsen score, and functional outcome was assessed by the Health Assessment Questionnaire (HAQ). Data were analyzed by multiple regression analyses, with correction for age and disease duration.
  
  
  RESULTS
  Ever having smoked was associated with a worse radiographic and functional outcome than was never having smoked. Both past and current smoking were associated with increased disease severity. Stratification by GSTM1 status revealed that polymorphism at this locus affected the relationship between smoking and disease outcome measures. Patients who lacked the GSTM1 gene and had ever smoked had significantly higher Larsen and HAQ scores than did those who lacked the gene and had never smoked. Radiographic outcome in these patients was worse than that in patients who had the GSTM1 gene and who had smoked. The associations were not affected by correction for socioeconomic status. Rheumatoid factor (RF) production was found to be associated with smoking in only the GSTM1-null patients.
  
  
  CONCLUSIONS
  Our data suggest that disease outcome in female RA patients with a history of smoking is significantly worse than in those who have never smoked. Smoking was associated with the most severe disease in patients who carried the GSTM1-null polymorphism. This association may be due in part to a relationship between the GSTM1 polymorphism and RF production in smokers.
authors.affiliation: Staffordshire Rheumatology Centre, Stoke-on-Trent, UK. d.l.mattey@keele.ac.uk
authors.forename: Derek L
authors.initials: DL
authors.lastname: Mattey
authors.forename: David
authors.initials: D
authors.lastname: Hutchinson
authors.forename: Peter T
authors.initials: PT
authors.lastname: Dawes
authors.forename: Nicola B
authors.initials: NB
authors.lastname: Nixon
authors.forename: Sheila
authors.initials: S
authors.lastname: Clarke
authors.forename: June
authors.initials: J
authors.lastname: Fisher
authors.forename: Ann
authors.initials: A
authors.lastname: Brownfield
authors.forename: Julie
authors.initials: J
authors.lastname: Alldersea
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Fryer
authors.forename: Richard C
authors.initials: RC
authors.lastname: Strange
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D006304:Health Status; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000502:physiology*; D012217:Rheumatoid Factor / Q000096:biosynthesis; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects*; D012923:Social Class; D011795:Surveys and Questionnaires
chemical_list: D005982:Glutathione Transferase; D012217:Rheumatoid Factor