Genetic polymorphisms in the Interleukins IL1B, IL4, and IL6 are associated with concomitant periodontitis and type 2 diabetes mellitus in Brazilian patients

Abstract

Objective: To assess whether single nucleotide polymorphisms (SNPs) in the IL10, IL1A, IL1B, IL4, TNFA, IL6, OPG, RANK, and RANKL genes, "classically" related with periodontitis, could be associated with susceptibility to T2DM, and also with both diseases concomitantly. Background: There are common pathogenic mechanisms in type 2 diabetes mellitus (T2DM) and periodontitis, but the knowledge of the genetic aspect of this is limited. In patients affected by concomitant T2DM and periodontitis, whose incidence is increasing, there is scarce information regarding the gene-phenotype association, including whether there are genes able to influence both diseases as comorbidities. Methods: Periodontal clinical parameters and biochemical profile (Insulin, Fasting Glycemia, HbA1c, Triglycerides, Total Cholesterol, HDL-cholesterol, and LDLcholesterol) data were obtained from 894 individuals divided into following three groups: Healthy (H; n = 347), Periodontitis (P; n = 348), and Periodontitis + T2DM (P + T2DM; n = 199). DNA from oral epithelial cells was collected for genotyping. Associations between SNPs and pathologies were tested by multiple logistic regression models, adjusting for age, sex, and smoking habits. We also investigated whether there are sex or smoking effects of each SNP in these phenotypes. Results: The rs1143634-GA (IL1B) SNP showed significantly less likely to develop P + T2DM for all population and mainly for women (adjusted OR = 0.37, 95% CI = 0.16-0.88), while women carrying the rs224320 CT (IL4) were more susceptible to develop P + T2DM (adjusted OR = 1.81, 95% CI = 1.04-3.15). Men carrying the rs1800795-CC (IL6) genotype were less likely to develop T2DM (adjusted OR = 0.12, 95% CI = 0.02-0.70, P = .01). Conclusions: Some SNPs in the IL1B, IL4, and IL6 genes demonstrated sex-influenced association with concomitant periodontitis and T2DM, increasing the evidence of a common genetic component between these diseases and contributing with the understanding of their common pathogenic mechanisms. | 919 CIRELLI Et aL.

Independent impact of periodontitis and cardiovascular disease on elevated soluble urokinase‐type plasminogen activator receptor (suPAR) levels

“…Recently, some translational scientific reports have shown a strong association between periodontitis and certain systemic inflammatory diseases, such as rheumatoid arthritis, diabetes, and cardiovascular diseases (CVD), for instance coronary heart disease (CHD), endothelial dysfunction, and stroke 5,6 . Furthermore, several large scale prospective studies have highlighted that periodontitis represents a strong increased risk factor for diabetes, CVD, CHD, stroke, and myocardial infarction 3,7–9 .…”

Deregulation of lncRNA HIST1H2AG-6 and AIM1-3 in peripheral blood mononuclear cells is associated with newly diagnosed type 2 diabetes

“…It has been reported that with CADM1, an immunoglobulin superfamily member, ectodomain shedding contributed to blood glucose dysregulation in T2DM [ 38 ]. Gene variants or polymorphisms of IL1B and ENP1 have been found to correlate with T2DM in many human studies [ 39 – 41 ]. Moreover, starch and sucrose metabolism and MAPK signaling pathways have been implicated in the development of T2DM in multiple animal models and human studies [ 42 , 43 ].…”

Polymorphisms in Genes of Lipid Metabolism Are Associated with Type 2 Diabetes Mellitus and Periodontitis, as Comorbidities, and with the Subjects’ Periodontal, Glycemic, and Lipid Profiles

“…A complete periodontal examination of all subjects assessed the following clinical signs and parameters at four interproximal sites around each tooth: probing pocket depth (PPDi) and clinical attachment level (CALi), measured to the nearest millimeter by a UNC-15 periodontal probe (Millennium®) and the presence of visible plaque, marginal bleeding and bleeding on probing (BOP) [ 32 , 33 ]. The last three parameters were registered as a percentage of the total number of interproximal sites assessed.…”