title: Association of the -2849 interleukin-10 promoter polymorphism with autoantibody production and joint destruction in rheumatoid arthritis.
abstract: OBJECTIVE
  To analyze the -2849 A/G interleukin-10 (IL-10) promoter polymorphism, which is associated with high (AG/GG) and low (AA) IL-10 production, in a cohort of rheumatoid arthritis (RA) patients and controls in order to gain a better understanding of its role in the incidence and progression of RA.
  
  
  METHODS
  Allele frequencies of the promoter polymorphism -2849 A/G and carriage rates were compared in 283 RA patients, 413 patients with other rheumatic diseases, and 1,220 healthy controls. The rate of joint damage and baseline levels of IgG and IgM rheumatoid factors and anti-citrullinated peptide antibodies were measured and were correlated with the IL-10 gene polymorphism. Furthermore, the correlation between the invasiveness of fibroblast-like synoviocytes (FLS) and the -2849 IL-10 genotype was tested.
  
  
  RESULTS
  The IL-10 genotype was not associated with the incidence of RA, but instead, correlated with disease progression, as determined by the extent of joint destruction. A higher rate of joint destruction was observed in patients with the genotype associated with high IL-10 production. Since FLS are thought to be involved in joint destruction, we analyzed IL-10 genotypes in conjunction with FLS invasiveness. Although adenoviral gene transfer of IL-10 to FLS inhibited their invasiveness, no differences were observed in vitro in the FLS from RA patients who were -2849 non-G carriers compared with those who were G carriers. Instead, patients with the -2849 AG/GG genotype, which is associated with high IL-10 production, had higher autoantibody titers at baseline.
  
  
  CONCLUSIONS
  The -2849 IL-10 promoter polymorphism is associated with autoantibody production and subsequent joint damage in RA.
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: L R
authors.initials: LR
authors.lastname: Lard
authors.forename: F A
authors.initials: FA
authors.lastname: van Gaalen
authors.forename: J J M
authors.initials: JJ
authors.lastname: Schonkeren
authors.forename: E J
authors.initials: EJ
authors.lastname: Pieterman
authors.forename: G
authors.initials: G
authors.lastname: Stoeken
authors.forename: K
authors.initials: K
authors.lastname: Vos
authors.forename: R G H H
authors.initials: RG
authors.lastname: Nelissen
authors.forename: R G J
authors.initials: RG
authors.lastname: Westendorp
authors.forename: R C
authors.initials: RC
authors.lastname: Hoeben
authors.forename: F C
authors.initials: FC
authors.lastname: Breedveld
authors.forename: R E M
authors.initials: RE
authors.lastname: Toes
authors.forename: T W J
authors.initials: TW
authors.lastname: Huizinga
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D015994:Incidence; D016753:Interleukin-10 / Q000235:genetics*; D007596:Joints / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D001323:Autoantibodies; D016753:Interleukin-10