Host genetic predispositions to dysregulated immune response can influence the development of the aggressive form of periodontitis (AgP) through susceptibility to oral dysbiosis and subsequent host-microbe interaction. This case-control study aimed to perform a multilocus analysis of functional variants in selected interleukin (IL) genes in patients with the generalized form of AgP in a homogenous population. Twelve polymorphisms in IL-1 gene cluster, IL-6 and its receptor, IL-10, IL-17A, and IL-18 were determined in 91 AgP patients and 210 controls. Analysis of seven selected periodontal bacteria in subgingival sulci/pockets was performed with a commercial DNA-microarray kit in a subgroup of 76 individuals. The pilot in vitro study included stimulation of peripheral blood monocytes (PBMC) from 20 individuals with periodontal bacteria and measurement of IL-10 levels using the Luminex method. Only the unctional polymorphism IL‑10-1087 A/G (rs1800896) and specific IL-10 haplotypes were associated with the development of the disease (P < 0.05, Pcorr > 0.05). Four bacterial species occurred more frequently in AgP than in controls (P < 0.01, Pcorr < 0.05). Elevated IL-10 levels were found in AgP patients, carriers of IL‑10-1087GG genotype, and PBMCs stimulated by periodontal bacteria (P < 0.05, Pcorr > 0.05). We therefore conclude that a combination of genetic predisposition to the altered expression of IL-10 and the presence of specific periodontal bacteria may contribute to Th1/Th2 balance disruption and AgP development.

• Keywords
• aggressive periodontitis, genetic predisposition, inflammation, interleukin, oral bacteria, polymorphism,
• MeSH
• Aggressive Periodontitis genetics   immunology   microbiology   MeSH
• Alleles MeSH
• Bacteria genetics   MeSH
• Adult MeSH
• Gene Frequency genetics   MeSH
• Genetic Predisposition to Disease genetics   MeSH
• Genotype MeSH
• Haplotypes genetics   MeSH
• Interleukin-1 genetics   MeSH
• Interleukin-10 genetics   MeSH
• Interleukin-17 genetics   MeSH
• Interleukin-18 genetics   MeSH
• Interleukin-6 genetics   MeSH
• Interleukins genetics   metabolism   MeSH
• Polymorphism, Single Nucleotide genetics   MeSH
• Humans MeSH
• Periodontitis genetics   immunology   MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• Names of Substances
• Interleukin-1 MeSH
• Interleukin-10 MeSH
• Interleukin-17 MeSH
• Interleukin-18 MeSH
• Interleukin-6 MeSH
• Interleukins MeSH

Recent studies have suggested a bidirectional relationship between chronic periodontitis (CP) and diabetes mellitus (DM). Immunoregulatory factors such as cytokines play an important role in etiopathogenesis of both diseases. The aim of this study was to analyze variability in interleukin-1 (IL-1) gene cluster and IL-1β plasma levels in patients with CP, DM, and a combination of both diseases. A total of 1016 individuals participating in this case-control study-225 healthy controls, 264 patients with CP, 132 with type 1 diabetes (T1DM), and 395 patients with type 2 diabetes (T2DM)-were genotyped using methods based on polymerase chain reaction for IL-1 gene polymorphisms (IL-1A (-889C/T, rs1800587), IL-1B (+3953C/T, rs1143634), and IL-1RN (gene for IL-1 receptor antagonist, IL-1RA, 86 bp tandem repeats in intron 2)). Levels of IL-1β were measured by Luminex methods in subgroups of controls, CP, T1DM + CP, and T2DM + CP subjects. Although no significant associations were found in the genotype and allele frequencies of IL-1A (-889C/T), significant differences in the allele frequencies of IL-1B (+3953C/T) were observed between controls and CP patients (P < 0.05). In T1DM patients, IL-1RN ∗ S "short" allele and IL-1RN 12 genotype were significantly less frequent than those in controls (P < 0.01). In haplotype analysis, TTL haplotype decreased the risk of CP development (P < 0.01), whereas CCS and CTL haplotypes (P < 0.01 and P < 0.05) were associated with T1DM. Although IL-1β levels were measured significantly higher in mononuclear cells after stimulation by mitogens, HSP70, or selected periodontal bacteria than in unstimulated cells, IL-1 genotypes did not correlate with circulating IL-1β levels. In the Czech population, significant associations between the IL-1B polymorphism with CP and the IL-1RN variant with T1DM were found. Haplotype analysis suggests that variability in IL-1 gene cluster may be one of the factors in the CP and T1DM pathogenesis, although single variants of these polymorphisms are not substantial for protein production.

• Publication type
• Journal Article MeSH