The combined genotypes of stimulatory and inhibitory Fc gamma receptors associated with systemic lupus erythematosus and periodontitis in Japanese adults

Background: The pathobiology of systemic lupus erythematosus (SLE) is similar to that of periodontitis in that the immunoglobulin G Fc receptor (Fc gamma R) and proinflammatory cytokines play an important role. Genetic variations of Fc gamma R and interleukin (IL)-1 are associated with susceptibility to both diseases. Therefore, we evaluated whether the combination of Fc gamma R or IL-1 polymorphic genes represents a common risk factor for SLE and periodontitis. Methods: The study population consisted of Japanese adults with SLE and periodontitis (SLE+P group; n = 46), SLE only (SLE group; n = 25), periodontitis only (P group; n = 58), and healthy individuals with no systemic or oral disease (H group; n = 44). Clinical periodontal condition was evaluated by measurement of probing depth, clinical attachment level, and alveolar bone loss. Genomic DNA was isolated from peripheral blood and analyzed for determination of Fc gamma R genotypes (Fc gamma RIIA, Fc gamma RlIB, Fc gamma RIIIA, and Fc gamma RIIIB) and IL-1 genotypes (IL-1A +4845 and IL-1B +3954) by allele-specific polymerase chain reactions or DNA sequencing. Results: A significant overrepresentation of the R 131 allele of stimulatory Fc gamma RIIA and the 232T allele of inhibitory Fc gamma RIIB was found in the SLE+P group compared to the H group (P=0.01 and P=0.0009, respectively). The combination of Fc gamma RIIA-R131 and Fc gamma RIIB-232T alleles yielded a strong association with SLE and periodontitis (SLE+P group versus P group: P=0.01, odds ratio: 3.3; SLE+P group versus H group: P = 0.0009, odds ratio: 11.2). Furthermore, SLE patients with the combined Fc gamma R risk alleles exhibited more severe periodontal tissue destruction compared to other SLE patients. The frequencies of IL-1 polymorphic alleles were too low to assess the association with SLE or periodontitis. Conclusion: The combination of stimulatory Fc gamma RIIA and inhibitory Fc gamma RIIB genotypes may increase susceptibility to SLE and periodontitis in the Japanese population.