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

Josiane Bazzo De Alencar,Joana Maira Valentini Zacarias,Jeane Eliete Laguila Visentainer,Cléverson De Oliveira E Silva,Victor Hugo De Souza,Patrícia Yumeko Tsuneto,Ana Maria Sell,David M Ojcius

doi:10.1371/journal.pone.0227905

Josiane Bazzo De Alencar, Joana Maira Valentini Zacarias + Show 6 more

Open Access

https://doi.org/10.1371/journal.pone.0227905

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Journal: PloS one	Publication Date: Jan 24, 2020
Citations: 32	License type: CC BY 4.0

Affiliation: Universidade Estadual de Maringá

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.

Highlights

Periodontitis (PD) is a common infectious disease in the oral cavity, affecting about 20–50% of the population in the world [1,2]
The influence of NLRP3, IL1B and IL2 polymorphisms in the development of PD have been reported in other populations [11,55], this is the first study involving these single nucleotide polymorphisms (SNPs) in PD patients and controls from southern of Brazil
We found that NLRP3 T/C genotype, IL1B -511 T/T genotype and IL2 GT (+166, -330) haplotype were associated to susceptibility to PD, regardless of smoking habits

Summary

Introduction

Periodontitis (PD) is a common infectious disease in the oral cavity, affecting about 20–50% of the population in the world [1,2]. Interleukin (IL)-1, IL-8 and tumor necrosis factor (TNF)-α, produced by fibroblasts, promote neutrophils chemotaxis in the inflamed periodontal site. TNF-α in synergism with IL-6 promotes osteoclast differentiation and IL-6 can stimulate the stromal cells to produce RANKL. These cytokines promote bone resorption in PD [16]. IL-4 and IL-10 have supressive properties and can attenuate the tissue distruction in PD. They were found in lower concentrations in the biological fluids of PD patients [18]

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