Tumor necrosis factor-alpha gene (TNF-α)-1031/-863,-857 single-nucleotide polymorphisms (SNPs) are associated with severe adult periodontitis in Japanese
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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DOI：
10.1034/j.1600-051x.2003.00287.x
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发表时间：
2003-06-01
影响因子：
6.7
通讯作者：
Murayama, Y
中科院分区：
文献类型：
--
作者：
Soga, Y;Nishimura, F;Murayama, Y
目的：肿瘤坏死因子-α(TNF-α)和白介素1-β(IL-1β)参与了牙周炎炎症病变的形成。这些细胞因子的高分泌可能与牙周炎的严重程度有关。已经有几项研究检验了牙周炎和影响细胞因子生产力的单核苷酸多态(SNPs)之间的联系。最近，发现了新的肿瘤坏死因子-α、-1031、-863和-857单核苷酸多态，其变异在日本人中占较大比例。这些SNPs的变异等位基因被认为与高水平的肿瘤坏死因子-α产生有关。为了更好地了解与牙周炎严重程度相关的遗传因素，包括这些新发现的SNPs的进一步分析是必要的。此外，以前关于与牙周炎相关的TNF-α或IL-1βSNPs的报道主要针对高加索人群。因此，本研究旨在探讨日本人重度牙周炎与以下SNP的关系：5个位于肿瘤坏死因子-α基因启动子(-1031、-863、-857、-308、-238)的SNP和3个位于IL-1β基因(-511、-31、+3953)的SNP。受试者为重度成人牙周炎患者和健康者。采用聚合酶链式反应-限制性片段长度多态性方法对所有受试者进行肿瘤坏死因子-α和白介素1-β单核苷酸多态基因分型。结果：TNF-α-1031/-863(连锁不平衡)或-857 SNP变异等位基因携带者产生的肿瘤坏死因子-α倾向于升高，且重度牙周炎患者携带至少一个变异等位基因的频率显著高于健康对照组。结论：牙周炎患者中携带至少一个变异等位基因的牙周炎患者中，-863或-857 SNP变异等位基因的频率明显高于健康对照组在日本人群中，肿瘤坏死因子-α-1031、-863和-857单核苷酸多态似乎与严重的成人牙周炎有关。
Objectives: 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.