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Genetic variants at multiple loci have been shown to be associated with susceptibility to periodontitis. To better assess the genetic risk factors for periodontitis, we performed a case-control study in 319 Japanese individuals with periodontitis (172 aggressive and 147 chronic disease) and 303 race-matched healthy control individuals. Thirty-five functional gene polymorphisms that had been previously associated with immune responses were genotyped. For all gene polymorphisms tested, no significant differences were observed in the allele frequencies of persons with aggressive, chronic, and combined (aggressive and chronic) periodontitis, compared with control individuals. Multiple logistic regression analysis revealed a significant association of the vitamin D receptor +1056 T/C polymorphism with susceptibility to chronic periodontitis, after adjustment for age, gender, and smoking status (P = 0.002). These results suggest that none of the polymorphisms tested was strongly associated with periodontitis in a Japanese population. However, the vitamin D receptor +1056 polymorphism may be related to chronic periodontitis.

Objectives: The expression of interleukin (IL)-12Rbeta2 molecule is a crucial regulatory factor in the T-helper type (Th) 1 differentiation of T cells. To elucidate the role of the cell-mediated immune (CMI) response in the pathogenesis of periodontitis, Japanese periodontal patients were subjected to single nucleotide polymorphism (SNP) analyses of the 5' flanking region of IL12RB2, whose variants are frequently detected in lepromatous leprosy patients, in which the very weak cellular immune response is caused by low expression of IL-12Rbeta2., Material and Methods: The gene polymorphisms of the 5' flanking region of IL12RB2 were examined in subjects with several types of periodontal disease and in healthy controls. Serum immunoglobulin (Ig) G antibody titres against periodontopathic bacteria were measured and compared in periodontal patients with and without variant alleles of IL12RB2., Results: The frequencies of variant alleles of IL12RB2 were significantly higher in aggressive periodontitis patients as compared with healthy controls or chronic periodontitis patients. Serum IgG titres against all periodontal bacteria examined in subjects carrying variant alleles were higher than those in subjects without variant alleles., Conclusion: IL-12Rbeta2 SNPs could be useful as genetic markers to access the susceptibility of the general population to periodontal disease. Low CMI responses or high humoral responses are associated with the pathogenesis of inflammatory periodontal diseases.

Background and Objective: Aggressive periodontitis (AgP) is a specific type of periodontal disease that is characterized by rapid attachment loss and bone destruction. While attempting to identify genetic polymorphisms associated with AgP, previous research has focused on candidate genes that may be involved in immune responses to microbial infections. In this study, the focus was on single nucleotide polymorphisms (SNPs) in the key mediators of osteoclast differentiation and activation, which involve receptor activator of nuclear factor-kappaB (RANK), RANK ligand (RANKL) and osteoprotegrin (OPG), in the Japanese population. The aim of this study was to evaluate the association of RANK/RANKL/OPG gene polymorphisms with AgP in the Japanese population., Material and Methods: We examined 99 patients with AgP and 89 controls from the Japanese population to explore the possibility of RANK/RANKL/OPG loci as candidate regions associated with the disease. All exons and relevant exon-intron boundaries of these three candidate genes were amplified by polymerase chain reaction (PCR) using 19 primers, followed by direct sequencing. The polymorphisms were identified by comparing the sequences obtained from 48 subjects., Results: We identified 27 SNPs in RANK, including 10 novel SNPs and seven SNPs each in both RANKL and OPG. A pairwise linkage disequilibrium analysis using the r2 statistic showed that some SNP pairs from the three loci are in tight linkage disequilibrium., Conclusion: An association analysis with allelotypes showed that SNPs identified in the RANK/RANKL/OPG genes have no significant association with AgP in the Japanese population.

Objective: To investigate the relationship between estrogen receptor (ER) and vitamin D receptor (VDR) gene polymorphisms and tooth loss, oral bone loss, and postcranial bone mineral density (BMD) in Japanese postmenopausal women., Design: Polymorphisms at the ER PvuII and XbaI and VDR BsmI gene sites, number of teeth remaining, oral bone mass, and BMD of the lumbar spine and the hip were evaluated in 149 Japanese postmenopausal women., Results: The distribution of ER PvuII and XbaI and VDR BsmI restriction fragment length polymorphisms was as follows: pp, 30.2%; Pp, 49.7%; PP, 20.1%; xx, 71.8%; Xx, 22.5%; XX, 2.7%; bb, 76.5%; Bb, 22.2%; and BB, 1.3%. Analysis of covariance adjusted for confounding variables revealed that participants with pp allele had fewer teeth remaining than did those with P allele. There were no significant differences in oral bone mass and postcranial BMD among three alleles at the PvuII site. Participants with X and bb allele had less oral bone mass and lower postcranial BMD than did those with xx and B allele, respectively. We could not clarify the positive associations between XbaI and BsmI polymorphism and number of teeth., Conclusions: PvuII polymorphism was associated with tooth loss, but not with oral bone mass and postcranial BMD. XbaI and BsmI polymorphisms may be associated with bone mass or density; however, PvuII polymorphism might contribute to another unknown pathway related to tooth loss.

Background: Functional polymorphisms of immunoglobulin G (IgG) Fc receptors (Fc gamma R) have been shown to be associated with generalized aggressive periodontitis (GAgP) or recurrence of chronic periodontitis (CP) in Japanese patients. The purpose of this study was to evaluate whether Fc gamma R polymorphisms are also associated with severity of CP., Methods: Fifty Japanese non-smoking patients with severe CP and 39 Japanese non-smoking patients with moderate CP were identified according to established clinical criteria, including measurements of probing depth (PD), clinical attachment level (CAL), and alveolar bone loss (BL). Fc gamma R genotypes for 3 bi-allelic polymorphisms (Fc gamma RIIa-R/H131, Fc gamma RIIIa-158V/F, Fc gamma RIIIb-NA1/NA2) were determined in these CP patients and 64 race-matched, non-smoking healthy controls by means of allele-specific polymerase chain reactions., Results: There was a significant over-representation of Fc gamma RIIIa-158V allele in severe CP patients compared to moderate CP patients (odds ratio 2.03, 95% confidence interval [CI] 1.03-4.01, chi 2 = 4.86, P = 0.028). In addition, we found a strong association between CP severity and Fc gamma R composite genotype comprising Fc gamma RIIIa-158V plus Fc gamma RIIIb-NA2 (severe CP versus moderate CP: odds ratio 4.69, 95% CI 1.52-15.10, chi 2 = 9.35, P = 0.002; severe CP versus healthy controls: odds ratio 4.10, 95% CI 1.62-10.59, chi 2 = 11.13, P = 0.0009). Moreover, CP patients positive for the composite genotype exhibited more severe signs of periodontitis than composite genotype-negative individuals (positive versus negative; mean PD: 3.8 mm versus 3.2 mm, P = 0.005; mean CAL: 4.5 mm versus 3.7 mm, P = 0.005; mean % BL: 37.6% versus 29.9%, P = 0.008)., Conclusion: Our results document the Fc gamma RIIIa-158V allele and possibly Fc gamma RIIIb-NA2 to be associated with severity of CP in Japanese patients.