WNT gene polymorphisms and predisposition to apical periodontitis

Letícia Chaves de Souza,Gustavo P Garlet,Ariadne Letra,Lorena Maili,Franco Cavalla,Alexandre R Vieira,Renato M Silva

doi:10.1038/s41598-019-55293-6

Abstract

Single nucleotide polymorphisms (SNPs) in WNT genes may impact gene/protein function and contribute to individual predisposition to apical periodontitis (AP). Here, we investigated the association of SNPs in/nearby WNT3, WNT3A, WNT5A, WNT8A, WNT9B and WNT11 genes with AP using a case-control dataset. Cases were defined as individuals with deep caries and AP (n = 188); controls had deep caries and no AP (n = 230). Genotyping was performed using Taqman chemistry in real time PCR. Data analyses was performed using Fisher Exact tests assuming a Bonferroni correction threshold value of 0.005. Single-SNP association analysis revealed a trend for association with WNT3 rs9890413 genotypes (P = 0.009) under a dominant model and allelic association for WNT3A rs1745420 (P = 0.009). Haplotypes involving WNT3-WNT9B-WNT3A alleles were also significantly associated with AP (P ≤ 0.003). Luciferase reporter assays showed higher transcriptional activity (1.4-fold) with the alternate G allele in rs1745420. Expression of WNT3, WNT3A and WNT5A in AP tissues was significantly higher than in control tissues, and inversely correlated with the expression of SERPINB1, COL1A1 and TIMP1 (P < 0.05). Our results suggest that WNT genes have a role in modulating AP and polymorphisms in these genes may increase susceptibility to AP.

Highlights

Single nucleotide polymorphisms (SNPs) in WNT genes may impact gene/protein function and contribute to individual predisposition to apical periodontitis (AP)
Endodontic pathogens present in teeth diagnosed with pulp necrosis and AP have been associated with the expression of mediators related to soft tissue and bone destruction in AP, such as matrix metalloproteinases (MMPs)-2 and -9, receptor activator of NFκB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG)
We investigated the mRNA expression of the associated genes WNT3, WNT3A, Wnt family member 5 A (WNT5A), WNT9B in AP lesion tissues using quantitative RT-PCR

Summary

Introduction

Single nucleotide polymorphisms (SNPs) in WNT genes may impact gene/protein function and contribute to individual predisposition to apical periodontitis (AP). Endodontic pathogens present in teeth diagnosed with pulp necrosis and AP have been associated with the expression of mediators related to soft tissue and bone destruction in AP, such as matrix metalloproteinases (MMPs)-2 and -9, receptor activator of NFκB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG) These findings suggest a dynamic process between the microbial aggression and host responses during AP development[3]. In accordance with these previous studies, single nucleotide polymorphisms (SNPs) in disease-relevant genes, mostly belonging to immune-response related pathways, have recently been reported in association with AP predisposition[4,5,6]. Additional studies showed the upregulation of WNT gene expression during periapical lesion development, and suggested that the AP-induced inflammation inhibits osteoblast differentiation via modulation of Wnt/β-catenin signaling pathway[8,10,11]

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Results

Conclusion