title: Fcgamma receptor type IIIA is associated with rheumatoid arthritis in two distinct ethnic groups.
abstract: OBJECTIVE
  To investigate a possible association between a functional polymorphism in the intermediate-affinity receptor for IgG called Fc-gamma receptor type IIIA (FcgammaRIIIA [CD16]) and rheumatoid arthritis (RA).
  
  
  METHODS
  This was an allelic association study in which a single nucleotide polymorphism in FcgammaRIIIA was examined as a susceptibility and/or severity factor for RA. The FcgammaRIIIA-158V/F polymorphism was genotyped by direct sequencing in 2 well-characterized ethnic groups, UK Caucasians (141 RA patients and 124 controls) and North Indians and Pakistanis (108 RA patients and 113 controls).
  
  
  RESULTS
  The FcgammaRIIIA-158V/F polymorphism was associated with RA in both ethnic groups (P = 0.028 for UK Caucasians, P = 0.050 for North Indians and Pakistanis, and P = 0.003 for both groups combined). FcgammaRIIIA-158VF and -158W individuals had an increased risk of developing RA in both populations (UK Caucasians odds ratio [OR] 1.6, P = 0.050; North Indians and Pakistanis OR 1.9, P = 0.023; and combined groups OR 1.7, P = 0.003). In the UK Caucasian group, the highest risk was for nodular RA, a more severe disease subset, associated with homozygosity for the FcgammaRIIIA-158V allele (OR 4.4, P = 0.004). There was also evidence for an interaction between the RA-associated HLA-DRB1 allele and the presence of at least 1 FcgammaRIIIA-158V allele in predicting susceptibility to RA (OR 5.5, P = 0.000).
  
  
  CONCLUSIONS
  We have demonstrated that the FcgammaRIIIA-158V/F polymorphism is a susceptibility and/or severity marker for RA in 2 distinct ethnic groups. This finding may ultimately provide additional insights into the pathogenesis of RA and other autoantibody/immune complex-driven autoimmune diseases.
authors.affiliation: University of Leeds, UK.
authors.forename: A W
authors.initials: AW
authors.lastname: Morgan
authors.forename: B
authors.initials: B
authors.lastname: Griffiths
authors.forename: F
authors.initials: F
authors.lastname: Ponchel
authors.forename: B M
authors.initials: BM
authors.lastname: Montague
authors.forename: M
authors.initials: M
authors.lastname: Ali
authors.forename: P P
authors.initials: PP
authors.lastname: Gardner
authors.forename: H C
authors.initials: HC
authors.lastname: Gooi
authors.forename: R D
authors.initials: RD
authors.lastname: Situnayake
authors.forename: A F
authors.initials: AF
authors.lastname: Markham
authors.forename: P
authors.initials: P
authors.lastname: Emery
authors.forename: J D
authors.initials: JD
authors.lastname: Isaacs
mesh_terms: D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D000939:Epitopes / Q000032:analysis; D005006:Ethnicity / Q000235:genetics*; D005838:Genotype; D006684:HLA-DR Antigens / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D007194:India / Q000453:epidemiology; D010154:Pakistan / Q000453:epidemiology; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics*; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D017452:Receptors, IgG