Human type II low-affinity receptor for immunoglobulin G (FcgammaRII) constitutes a clustered gene family consisting of FcgammaRIIA, IIB and IIC genes. FcgammaRIIB is unique in its ability to transmit inhibitory signals in B cells via immunoreceptor tyrosine-based inhibitory motif (ITIM). B-cell activation and subsequent elevated production of IgG are the immunopathological features of inflammatory disease such as periodontitis. To determine whether an association with periodontitis susceptibility exists, genetic polymorphisms of FcgammaRIIB were examined in Japanese patients with aggressive periodontitis (AGP) and chronic periodontitis (CP), and in the race-matched healthy controls (HCs). A significant difference was observed in the distribution of FcgammaRIIB-232I/T allele (exon 5) between the AGP and HC groups, with enrichment of the 232T in the AGP group (P=0.006). In addition, the FcgammaRIIB-nt 646-184A/G allele (intron 4) distribution was significantly different between the CP and HC groups, with enrichment of the nt 646-184A in the CP group (P=0.011). These results document the association of FcgammaRIIB gene polymorphisms with susceptibility to periodontitis in the Japanese.