IL-10-592 SNP is functional in chronic periodontitis

Periodontal diseases are infectious diseases, where periodontopathogens trigger chronic inflammatory and immune responses that determine the disease outcome. Inflammatory mediators, such as TNF-ƒŃ and IL-1ƒ", initiate tissue destruction through the generation of metalloproteinases, which degrade extracellular matrix, and the activation of mechanisms for bone resorption. Anti-inflammatory cytokines such as IL-10 seem to attenuate periodontal tissue destruction through the induction of tissue inhibitors of metalloproteinases (TIMPs) and the inhibitor of osteclastogenesis osteoprotegerin (OPG). A high individual variation in levels of IL-10 mRNA is verified in periodontitis patients, which is possibly determined by genetic polymorphisms. Objectives:The objective of this study was evaluate the influence of a genetic polymorphism in expression of IL-10, TIMPs and OPG, and correlate these data with clinical parameters. Methods: In this study the IL-10 promoter -592 C/A single nucleotide polymorphism (SNP), which is associated with a decrease in IL-10 production, was analyzed by restriction fragment length polymorphism (RFLP) in 116 chronic periodontitis (CP) patients and 58 control (C) subjects. In addition, the levels of IL-10, TIMPs and OPG mRNA expression in diseased gingival tissues were determined by RealTime-PCR. Results:The IL-10-592 SNP CA genotype was found to be significantly more prevalent in the CP group when compared with control subjects. CA and AA genotypes were associated with lower levels of IL-10, TIMP-3 and OPG mRNA expression in diseased periodontal tissues, and were also associated with higher mean probing depth in CP patients. Conclusions:Taken together, the results presented here demonstrate that IL-10-592 SNP is functional in CP, being associated with lower levels of IL-10 mRNA expression, which is supposed to consequently decrease TIMP-3 and OPG mRNA expression. Therefore, IL-10-592 SNP seems to be an important factor in the determination of periodontal disease severity, which supports its inclusion as one of the candidate markers of periodontitis risk.