title: FCRL3 -169C/C genotype is associated with anti-citrullinated protein antibody-positive rheumatoid arthritis and with radiographic progression.
abstract: OBJECTIVE
  Studies of Caucasian populations have shown conflicting results concerning the association between a promoter polymorphism -169T>C of the Fc receptor-like 3 (FCRL3) gene and rheumatoid arthritis (RA). It is unknown whether FCRL3 is associated with autoantibody status and disease severity. We investigated associations between FCRL3 -169T>C and autoantibody status and joint damage in patients with RA.
  
  
  METHODS
  A total of 652 Norwegian patients with RA from 2 cohorts and 981 Norwegian controls, previously genotyped for FCRL3 -169T>C (rs7528684), were studied. Data on anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) were available. The EURIDISS cohort (disease duration ≤ 4 yrs at baseline) was followed longitudinally, with assessment of radiographic hand damage at baseline and after 10 years (n = 117) according to the van der Heijde-modified Sharp score.
  
  
  RESULTS
  We found significant associations with ACPA-positive RA for both the C allele (OR 1.28, 95% CI 1.08-1.52, p = 0.004) and the C/C genotype (OR 1.57, 95% CI 1.18-2.10, p = 0.002). Similar associations were seen with RF-positive RA. No association was found with ACPA-negative or RF-negative RA. The C/C genotype was found to be associated with 10-year radiographic progression in multivariate linear and logistic regression analyses, after adjustment for ACPA, erythrocyte sedimentation rate, age, and sex.
  
  
  CONCLUSIONS
  The promoter polymorphism of FCRL3 was associated with autoantibody-positive RA. Despite the low number of patients, the C/C genotype of the FCRL3 polymorphism consistently and independently predicted radiographic progression. These findings suggest that FCRL3 is involved in both disease susceptibility and progression.
authors: Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. marthemaehlen@gmail.com
authors: Marthe T
authors: MT
authors: Maehlen
authors: Gry B
authors: GB
authors: Nordang
authors: Silje W
authors: SW
authors: Syversen
authors: Désirée M
authors: DM
authors: van der Heijde
authors: Tore K
authors: TK
authors: Kvien
authors: Till
authors: T
authors: Uhlig
authors: Benedicte A
authors: BA
authors: Lie
mesh_terms: D000328:Adult; D000483:Alleles; D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D001172:Arthritis, Rheumatoid / Q000208:ethnology / Q000235:genetics* / Q000276:immunology*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005838:Genotype; D050823:Hand Joints / Q000000981:diagnostic imaging; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009664:Norway; D010456:Peptides, Cyclic / Q000235:genetics / Q000276:immunology*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011859:Radiography; D011971:Receptors, Immunologic / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D000888:Antibodies, Anti-Idiotypic; C457775:FCRL3 protein, human; D010456:Peptides, Cyclic; D011971:Receptors, Immunologic; C487763:cyclic citrullinated peptide