Detection of association between periodontitis and polymorphisms of IL-1 beta+3954 and TNF-alpha-863 in the Korean population after controlling for confounding risk factors

Abstract

Background and Objective Interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha 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-1 alpha + 4845, IL-1 beta + 3954, and TNF-alpha -863, we aimed to investigate the relationship between periodontitis risk and the polymorphisms of IL-1 alpha/beta and TNF-alpha in Koreans. Material and Methods 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. Results Significant association of IL-1 beta + 3954 and TNF-alpha -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-1 beta + 3954 and increased risk of advanced periodontitis was consistently detected regardless of the status of self-reported diseases. In the polymorphism of TNF-alpha -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. Conclusion The results suggest that genetic variations of IL-1 beta + 3954 and TNF-alpha -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.