Gene–gene interaction among cytokine polymorphisms influence susceptibility to aggressive periodontitis

Abstract

Aggressive periodontitis (AgP) is a multifactorial disease. The distinctive aspect of periodontitis is that this disease must deal with a large number of genes interacting with one another and forming complex networks. Thus, it is reasonable to expect that gene-gene interaction may have a crucial role. Therefore, we carried out a pilot case-control study to identify the association of candidate epistatic interactions between genetic risk factors and susceptibility to AgP, by using both conventional parametric analyses and a higher order interactions model, based on the nonparametric Multifactor Dimensionality Reduction algorithm. We analyzed 122 AgP patients and 246 appropriate periodontally healthy individuals, and genotyped 28 polymorphisms, located within 14 candidate genes, chosen among the principal genetic variants pointed out from literature and having a role in inflammation and immunity. Our analyses provided significant evidence for gene-gene interactions in the development of AgP, in particular, present results: (a) indicate a possible role of two new polymorphisms, within SEPS1 and TNFRSF1B genes, in determining host individual susceptibility to AgP; (b) confirm the potential association between of IL-6 and Fc g-receptor polymorphisms and the disease; (c) exclude an essential contribution of IL-1 cluster gene polymorphisms to AgP in our Caucasian-Italian population.

Association analysis of the IL-1 gene cluster polymorphisms with aggressive and chronic periodontitis in the Algerian population

“…On the other hand, Gore et al, found that neutrophils from patients with advanced Page 10 of 20 A c c e p t e d M a n u s c r i p t periodontitis and carrying IL-1B (C+3954T) allele 2 produced increased IL-1b levels compared to patients without this allele but the differences were not significant (22). In contrast to other studies, Scapoli et al, conclude no association between AgP and IL1B gene was found in Italian Caucasian population (46), and a study of Galbraith et al, found no significant relationship between the genotype status and the level of cytokine production (47). While Santtila et al, found that allele 2 of the IL-1B polymorphism was associated with decreased IL-1b secretion (48).…”

Dexamethasone-induced selenoprotein S degradation is required for adipogenesis

“…Genetic variations of human SEPS1 located on chromosome 15q26.3, which was suggested to contain quantitative trait loci infl uencing infl ammation-related disorders such as type 2 diabetes, Alzheimer's disease, and celiac disease (45)(46)(47), were reported to be strongly associated with infl ammation in Mexican American individuals ( 13 ). Recently, variation in the SEPS1 gene locus has been reported to be associated with coronary heart disease ( 48 ), preeclampsia ( 49 ), gastric cancer ( 50 ), non-small cell lung cancer ( 51 ), and aggressive periodontitis ( 52 ). Some of the single nuclear polymorphisms in the SEPS1 gene were found in the conserved ERSE in the promoter region: this appears to alter inducibility of SEPS1 by ER stress and its Fig.…”

Variations in inflammatory genes are associated with periodontitis

“…A case–control study to identify the association of candidate genes epistatic interactions between genetic risk factors and susceptibility to aggressive periodontitis by using parametric analysis and higher order interaction models [20] has shown that: 1) within 14 candidate genes chosen in scientific literatures selenoprotein S (SEPS1) and tumor necrosis factor receptor superfamily member 1B (TNFRSF1B), have a possible role in determining host individual susceptibility to the disease; 2) an association between IL-6 and Fc-γ receptor polymorphism with periodontitis; 3) no the association of IL-1 cluster gene polymorphism with aggressive periodontitis.…”