Association of Fcγ receptor IIIB, but not of Fcγ receptor IIA and IIIA, polymorphisms with systemic lupus erythematosus in Japanese

Abstract

Human Fcγ receptor (FcγR) genes form a clustered gene family on chromosome 1q21–24. Although the association of FcγR polymorphisms with systemic lupus erythematosus (SLE) has been extensively studied, the results are often contradictory. In this study, FcγRIIA-131H/R, FcγRIIIA-176F/V and FcγRIIIB-NA1/2 genotypes were determined in the Japanese patients with SLE (n = 81) or rheumatoid arthritis (RA, n = 115) as well as in healthy individuals (n = 217), and possible association with the disease was tested using case-control analysis. Unlike in other populations, significant difference was not observed in the frequencies of FcγRIIA and FcγRIIIA genotypes between patients with SLE and healthy individuals. However, significant difference was detected in the frequencies of FcγRIIIB genotypes between SLE and healthy individuals (P = 0.008). The odds ratio [OR] of the FcγRIIIB-NA2/NA2 homozygotes for the development of SLE was 2.52 (95% confidence interval [CI]: 1.33–4.79). Among the patients with SLE, individuals with NA2/2 were significantly more likely to have lupus nephritis (P = 0.007). No association was observed between any of the FcγR polymorphisms and RA. Significant linkage disequilibrium was detected between FcγRIIIA and IIIB, but neither between IIA and IIIA, nor between IIA and IIIB. These observations may underscore the relevance of defective immune complex handling in the pathogenesis of SLE, or may suggest the presence of primarily associated gene(s) in linkage disequilibrium with FcγR genes.