title: HMOX1 promoter polymorphism modulates the relationship between disease activity and joint damage in rheumatoid arthritis.
abstract: OBJECTIVE
  The guanine-thymidine (GT)n repeat in the HMOX1 promoter determines the level of induction of the heme-degrading enzyme heme oxygenase 1 (HO-1), which protects against inflammatory and oxidative stress. In individuals with short (GT)n repeats (where n < 25; SS genotype), higher levels of HO-1 activity are induced more rapidly than in those with long (GT)n repeats (where n > or = 25; LL genotype). Recently, it was demonstrated that HO-1 activity protects against the onset of rheumatoid arthritis (RA). The aim of this study was to determine whether the (GT)n-repeat length within the HMOX1 promoter region is associated with RA disease severity and radiographic joint damage.
  
  
  METHODS
  A cohort of 325 well-characterized RA patients and 273 controls was investigated by DNA fragment-length analysis for the association of (GT)n repeats in the HMOX1 promoter region with RA disease susceptibility and severity.
  
  
  RESULTS
  Although no significant differences in genotype or allele frequency were found between controls and RA patients, the odds ratios corresponded well to those in the previously described cohort. Among patients, those carrying the SS genotype had a more favorable radiographic outcome over 9 years than those carrying the LL genotype. This was unexpected since no differences in disease activity were found between the genotypes or alleles.
  
  
  CONCLUSIONS
  Patients with the SS genotype have a better long-term radiographic outcome despite poor prognostic markers at baseline and despite disease activity at followup similar to that of patients with the LL genotype. This suggests that the HMOX1/HO-1 system is involved in the uncoupling of disease activity and joint damage and may provide a novel target for the treatment of RA.
authors.affiliation: Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. f.wagener@ncmls.ru.nl
authors.forename: Frank A D T G
authors.initials: FA
authors.lastname: Wagener
authors.forename: Erik J M
authors.initials: EJ
authors.lastname: Toonen
authors.forename: Lonneke
authors.initials: L
authors.lastname: Wigman
authors.forename: Jaap
authors.initials: J
authors.lastname: Fransen
authors.forename: Marjonne C W
authors.initials: MC
authors.lastname: Creemers
authors.forename: Timothy R D J
authors.initials: TR
authors.lastname: Radstake
authors.forename: Marieke J H
authors.initials: MJ
authors.lastname: Coenen
authors.forename: Pilar
authors.initials: P
authors.lastname: Barrera
authors.forename: Piet L C M
authors.initials: PL
authors.lastname: van Riel
authors.forename: Frans G M
authors.initials: FG
authors.lastname: Russel
mesh_terms: D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000235:genetics*; D004198:Disease Susceptibility; D005787:Gene Frequency; D005838:Genotype; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000502:physiology*; D011859:Radiography
chemical_list: C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1