Involvement of Fc gamma receptor IIIA genotypes in susceptibility to rheumatoid arthritis

Objective. To investigate a possible association of Fc gamma receptor IIIA (Fc gamma RIIIA) gene polymorphism at position 158 with susceptibility to, and the outcome of, rheumatoid arthritis (RA). Methods. One hundred seventeen RA patients and 142 unrelated healthy contro l subjects from the same geographic area were studied. Genotyping for Fc ga mma RIIIA-158V/F was performed by a method based on polymerase chain reacti on (PCR) and restriction fragment length polymorphism analysis using amplif ication-created restriction sites. HLA-DRB1 typing by PCR-sequence-specific oligonucleotide hybridization (reverse hybridization) was also performed. Results. Allele and genotype distributions in healthy controls were similar to those reported in other populations. The overall distribution of genoty pes in the patients was significantly different from that in the controls ( P = 0.023, by chi-square test from 3 x 2 contingency table). An overreprese ntation of the Fc gamma RIIIA-158FF genotype in the patients was observed ( for 158FF versus non-158FF P = 0.01, odds ratio [OR] 1.98, 95% confidence i nterval [95% CI] 1.16-3.4), However, the Fc gamma RIIIA-158VF genotype was increased in controls (for 158VF versus non-158VF P = 0.021, OR 0.54, 95% C I 0.32-0.92). No associations were found with any of a series of clinical p arameters. Analysis of Fc gamma RIIIA-158FF along with shared epitope showe d that the presence of both factors increased the susceptibility to RA (P = 0.0009, OR 3.6, 95% CI 1.63-8.01); however, they probably do not interact to produce this effect. Conclusion. These results indicate that the Fc gamma RIIIA-158 genotypes co nfer differential susceptibility to RA in our study population. Further stu dies to elucidate the role of this polymorphism in the pathogenesis of RA a nd other autoimmune diseases are warranted.