Fcgamma receptor type IIIA is associated with rheumatoid arthritis in two distinct ethnic groups.
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.
Morgan
A W
AW
University of Leeds, UK.
Griffiths
B
B
Ponchel
F
F
Montague
B M
BM
Ali
M
M
Gardner
P P
PP
Gooi
H C
HC
Situnayake
R D
RD
Markham
A F
AF
Emery
P
P
Isaacs
J D
JD
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
D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D017452:Receptors, IgG