Influence of inflammasome NLRP3, and IL1B and IL2 gene polymorphisms in periodontitis susceptibility

TLDR

Periodontitis involves immune molecules that can both eliminate pathogens and cause tissue destruction, yet the precise mechanisms remain unclear and genes related to inflammasomes and interleukin‑1 have been implicated. The study aimed to assess whether polymorphisms in NLRP3 inflammasome, cytokine, and cytokine‑receptor genes contribute to periodontitis susceptibility. A case‑control study of 186 periodontitis patients and 208 controls genotyped 20 SNPs by PCR‑RFLP/SSP, measured serum cytokines with Luminex, and analyzed associations with SNPStats and OpenEpi. Polymorphisms in NLRP3, IL1B, and IL2 were more frequent in periodontitis patients, especially in men, and carriers of multiple risk alleles had higher susceptibility than women.

Abstract

The pathogenesis of periodontitis (PD) involves several molecules of the immune system that interact in a network to eliminate the periodontopathogens, yet, they contribute to periodontal tissue destruction. The different mechanisms that lead to periodontal tissue damage are not clear. Despite this, immune response genes have been related to the development of PD previously, such as those involved in inflammasomes which are multiprotein complexes and cytokines including Interleukin-1. The aim of the study was to evaluate the polymorphisms in NLRP3 inflammasome, cytokine and receptor of cytokines genes in the development of periodontitis. This case-control study was conducted in 186 patients with PD (stage II and III and grade B) and 208 controls (localized gingivitis and periodontally healthy individuals). Genotyping was performed using PCR-RFLP for the SNP rs4612666 in NLRP3 and using PCR-SSP for IL1A, IL1B, IL1R, IL1RN, IL4RA, INFG, TGFB1, TNF, IL2, IL4, IL6, and IL10. Cytokine serum levels were measured using Luminex technology. SNPStats and OpenEpi software were used to perform statistical analysis. The higher frequencies of NLRP3 T/C and IL1B -511 T/T genotypes and IL2 (+166, -330) GT haplotype were observed in patients with PD compared to controls. The SNPs in NLRP3, IL1R +1970, IL6–174, TNF -308, IL2 +166 and -330, TGFB1 +869 and +915, IL4RA +1902, IL4–1098 and -590 were associated to PD in men. In conclusion, polymorphisms in NLRP3, IL1B and IL2 genes were associated to PD susceptibility. Men carrying the NLRP3, IL1R, IL6, TNF, IL2, TGFB1, IL4RA and IL4 polymorphisms had greater susceptibility than women for developing PD.