Early-onset periodontitis (EOP) is considered to have a genetic basis which has not been clearly defined. Genetic polymorphisms of the vitamin D receptor (VDR-B-b) and the immunoglobulin-Fc-gamma receptor IIIb (FcgammaRIIIb-NA1-NA2) are associated with bone metabolism and infectious diseases, respectively. The purpose of this study was to investigate the associations of EOP with VDR and FcgammaRIIIb polymorphisms. Subjects were comprised of those with generalized EOP (G-EOP, n = 42), adult periodontitis (AP, n = 52), and healthy control (HC, n = 55). VDR and FcgammaRIIIb genotypes were determined by allele-specific polymerase chain-reactions. Our results indicated that frequencies of the VDR-B non-carrier and the FcgammaRIIIb-NA2 carrier were lower in the G-EOP compared with the AP and HC groups. Furthermore, we found a strong association between G-EOP and the VDR-Fc-gammaRIIIb composite genotype (G-EOP vs. AP - OR = 5.09, p = 0.009; G-EOP vs. HC - OR = 5.93, p = 0.004). In conclusion, no correlation was found between the VDR genotype and G-EOP. However, the VDR and Fc-gammaRIIIb genotype combination may be associated with susceptibility to G-EOP.