Tumor necrosis factor‐alpha gene (TNF‐α) −1031/−863, −857 single‐nucleotide polymorphisms (SNPs) are associated with severe adult periodontitis in Japanese

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Abstract
Objectives: Tumour necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) 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‐α, −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‐α 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‐α or IL‐1β 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‐α gene promoter (−1031, −863, −857, −308, −238) and three in the IL‐1β 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‐α and IL‐1β SNPs were genotyped by polymerase chain reaction‐restriction fragment length polymorphism for all subjects. TNF‐α and IL‐1β production from LPS‐stimulated monocytes/macrophages was also measured for 15 healthy male subjects. Results: TNF‐α production in TNF‐α−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‐α–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‐α–1031, –863 or –857 SNPs was higher in periodontitis patients than in healthy subjects, TNF‐α−1031, −863 and −857 SNPs appear to be associated with severe adult periodontitis in Japanese populations.

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