Tumour
necrosis factor-alpha (
TNF-alpha) and
interleukin-1beta (IL-1beta) participate in the establishment of inflammatory lesions in
periodontitis. High production of these
cytokines may relate to the severity of
periodontitis. There have already been several studies examining the association between
periodontitis and single nucleotide polymorphisms (SNPs) that affect
cytokine productivity. Recently, new SNPs of
TNF-alpha, -1031, -863 and -857, variants of which are observed in a relatively large proportion in Japanese, have been identified. The variant alleles of these SNPs have been suggested to be related to high
TNF-alpha production. For a better understanding of the genetic factors associated with the severity of
periodontitis, further analysis including these newly identified SNPs is essential. In addition, previous reports on
TNF-alpha or IL-1beta SNPs associated with
periodontitis were mainly for Caucasian populations. Therefore, the aim of this study is to examine the association between severe
periodontitis in Japanese and the following SNPs: five in the
TNF-alpha gene promoter (-1031, -863, -857, -308, -238) and three in the IL-1beta gene (-511, -31, +3953).
MATERIAL AND METHODS: A total of 128 Japanese individuals were enrolled in this study. They were 64 patients with severe
adult periodontitis and 64 healthy subjects.
TNF-alpha and IL-1beta SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism for all subjects.
TNF-alpha and IL-1beta production from LPS-stimulated monocytes/macrophages was also measured for 15 healthy male subjects.
RESULTS:
TNF-alpha production in
TNF-alpha-1031/-863 (linkage disequilibrated) or -857 SNP variant allele carriers tended to be elevated, and the frequency of subjects who carried at least one variant allele in TNF-alpha-1031, -863 or -857 SNPs among severe
periodontitis patients was significantly higher than in healthy subjects.
CONCLUSION: Since the frequency of subjects who carried at least one variant allele in TNF-alpha-1031, -863 or -857 SNPs was higher in
periodontitis patients than in healthy subjects, TNF-alpha-1031, -863 and -857 SNPs appear to be associated with severe
adult periodontitis in Japanese populations.