Dental Research Institute, Pusan National University Dental Hospital, Yangsan, Republic of Korea.
Department of Periodontology, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea.
J Periodontal Res. 2020 Dec;55(6):905-917. doi: 10.1111/jre.12783. Epub 2020 Jul 3.
Interleukin (IL)-1 and tumor necrosis factor (TNF)-α are inflammatory cytokines that play an important role in periodontitis, and their genetic variations have been suggested to be associated with increased risk of periodontitis. Focusing on three single nucleotide polymorphisms (SNPs) of IL-1α + 4845, IL-1β + 3954, and TNF-α -863, we aimed to investigate the relationship between periodontitis risk and the polymorphisms of IL-1 α/β and TNF-α in Koreans.
Mouthwash samples from 548 subjects (135 controls without periodontitis, 387 generalized chronic periodontitis patients, and 26 generalized aggressive periodontitis patients) were collected for isolation of genomic DNA. Genotyping of selected SNPs was performed using real-time PCR. Univariable associations between the polymorphisms and periodontitis were assessed by chi-squared test or Fisher's exact test. To evaluate the association after controlling for confounding effects of various risk factors, we stratified the subjects according to the presence or absence of self-reported diseases and employed multiple logistic regression model to adjust for age, smoking status, and oral hygiene indices and behaviors.
Significant association of IL-1β + 3954 and TNF-α -863 polymorphisms with periodontitis was observed after adjusting for the confounding risk factors, but not in univariable association analysis. The significant association between genotype CT of IL-1β + 3954 and increased risk of advanced periodontitis was consistently detected regardless of the status of self-reported diseases. In the polymorphism of TNF-α -863, the genotype with minor allele (CA + AA) was significantly associated with periodontitis susceptibility, which was observed only in the subjects with self-reported diseases.
The results suggest that genetic variations of IL-1β + 3954 and TNF-α -863 are associated with increased risk of periodontitis in Koreans. In addition, our findings underscore the importance of controlling for confounding risk factors to detect significant association between genetic factors and risk of periodontitis. A further well-designed large-scale study is needed to warrant our results.
白细胞介素（IL）-1 和肿瘤坏死因子（TNF）-α 是炎症细胞因子，在牙周炎中起重要作用，其遗传变异被认为与牙周炎的风险增加有关。本研究聚焦于 IL-1α+4845、IL-1β+3954 和 TNF-α-863 三个单核苷酸多态性（SNP），旨在探讨韩国人群中 IL-1α/β 和 TNF-α 多态性与牙周炎风险的关系。
采集 548 名受试者（135 名无牙周炎对照者、387 名慢性牙周炎患者和 26 名侵袭性牙周炎患者）的漱口液样本，用于提取基因组 DNA。采用实时 PCR 方法对选定的 SNP 进行基因分型。采用卡方检验或 Fisher 确切检验评估多态性与牙周炎的单变量关联。为了评估在控制各种危险因素混杂效应后的关联，我们根据是否存在自我报告的疾病对受试者进行分层，并采用多变量逻辑回归模型调整年龄、吸烟状况和口腔卫生指数及行为因素。
在调整混杂危险因素后，观察到 IL-1β+3954 和 TNF-α-863 多态性与牙周炎显著相关，但在单变量关联分析中未观察到。IL-1β+3954 基因型 CT 与重度牙周炎风险增加显著相关，无论自我报告疾病的状态如何，这种关联均一致存在。在 TNF-α-863 多态性中，携带次要等位基因（CA+AA）的基因型与牙周炎易感性显著相关，仅在存在自我报告疾病的受试者中观察到这种关联。
研究结果提示，IL-1β+3954 和 TNF-α-863 的遗传变异与韩国人群牙周炎风险增加有关。此外，我们的研究结果强调了控制混杂危险因素以检测遗传因素与牙周炎风险之间的显著关联的重要性。需要进一步进行设计良好的大规模研究来验证我们的结果。
