Association of the FcγRIIB-nt645+25A/G polymorphism with the expression level of the FcγRIIb receptor, the antibody response to Porphyromonas gingivalis and the severity of periodontitis

Abstract

Human FcγRIIb is an immunoglobulin G (IgG) receptor that inhibits the activation of B lymphocytes through cross-linking with the B-cell receptor via immune complexes. This function acts as a negative regulator of antibody production. Our previous studies have demonstrated the gene polymorphisms in FcγRIIb to be associated with periodontitis. In this study, we presented a polymorphism--FcγRIIB-nt645+25A/G (rs2125685)--in intron 4 and analyzed its functional relevance to periodontitis. We examined whether the FcγRIIB-nt645+25A/G polymorphism is associated with periodontal parameters, the IgG response to the periodontopathic bacterium Porphyromonas gingivalis and/or the expression level of FcγRIIb on peripheral B lymphocytes. Thirty-two patients with chronic periodontitis were genotyped with nested PCR and by direct sequencing of genome DNA. The levels of serum IgG and of specific IgG subclasses for P. gingivalis sonicate and for the recombinant 40-kDa outer membrane protein (OMP) were determined. The expression levels of FcγRIIb on peripheral B lymphocytes from 19 healthy donors were measured by flow cytometry. Patients with the FcγRIIB-nt645+25AA genotype showed significantly higher mean clinical attachment levels compared to patients with the FcγRIIB-nt645+25GG genotype (p = 0.003) and a significantly lower IgG response to P. gingivalis sonicate and to the 40-kDa OMP. The expression levels of FcγRIIb protein on the cell surface in peripheral B lymphocytes were higher in healthy donors with the FcγRIIB-nt645+25AA genotype than in those with the FcγRIIB-nt645+25GG genotype (p = 0.03). The higher expression levels of FcγRIIb in subjects with the FcγRIIB-nt645+25AA genotype may induce a lower level of production of IgG against P. gingivalis and therefore more severe periodontitis.