Objectives: Aggressive periodontitis (AP), formerly early-onset periodontitis (EOP), is considered to have genetic basis, which have not been clearly defined. Two types of TNF receptor (TNFR) 1 and 2 mediate the interaction of TNF-a with its target cells, and its gene polymorphism as one of genetic factors may influence on the expression of several chronic inflammatory diseases. We have already reported the relationship between TNF-a gene polymorphisms and EOP (Endo et al. in press). Recently, it has been suggested that TNFRs may modulate TNF-a-mediated-inflammatory responses in periodontal diseases. The aim of the present study is to evaluate whether TNFRs gene polymorphisms are associated with AP patients in Japanese. Methods: Forty-seven generalized AP (G-AP) patients and 100 healthy controls in Japanese were identified according to established clinical criteria. Single nucleotide polymorphisms at positions -383(A/C) and +36(A/G) in the TNFR1 gene, and +587(T/G) and +694(G/A) in the TNFR2 gene and variable number of tandem repeats (VNTR) in the TNFR2 promoter region were detected by PCR, restriction fragment length polymorphisms, single strand conformation polymorphisms and direct sequencing methods. Results: Allele 2 frequencies in healthy controls were 6.5% at TNFR1(-383), 18.0% at TNFR1(+36), 9.0% at TNFR2(+587), 4.0% at TNFR2(+694), 80.5% at TNFR2(VNTR) respectively. The frequencies of TNFR1(+36) and TNFR2(VNTR) gene polymorphisms have been the first report in Japanese, and they tended to be much different from those of Caucasians. However, there were no significant differences in the genotype and allele frequencies when comparing G-AP patients with healthy controls. Conclusions: These findings suggest that there is not significant association between TNFRs gene polymorphisms and susceptibility to G-AP in Japanese patients. Supported by Grant-in Aids for Scientific Research (12771322) form the Ministry of Education, Science Sports and Culture of Japan.

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