Association Between Apical Periodontitis and TNF-α -308 G>A Gene Polymorphism: A Systematic Review and Meta-Analysis.

Alessandro Guimarães Salles,Erika Calvano Küchler,Lívia Azeredo Alves Antunes,Patrícia Arriaga Carvalho,Leonardo Santos Antunes

doi:10.1590/0103-6440201701491

Abstract

Currently, investigations have focused on the identification of Single Nucleotide Polymorphisms (SNP) involved in host response and its ability to generate an immunity deficiency. The aim of this study was to perform a systematic review (SR) and meta-analysis to evaluate the association between TNF-α -308 G>A polymorphism and apical periodontitis (AP) phenotypes. A broad search for studies was conducted. The following databases were used: PubMed, Scopus, Web of Science, and VHL (Medline, SciELO, Ibecs, and Lilacs). The MeSH terms "Periapical Periodontitis," "Periapical Abscess," "Polymorphism, Genetic," and "Polymorphism, Single Nucleotide" were used. MeSH synonyms, related terms, and free terms were included. Clinical investigations of individuals with different AP phenotypes in permanent teeth were selected. After application of the eligibility criteria, selected studies were qualified by assessing their methodological quality. A fixed effect model was used for the meta-analysis. The initial search identified 71 references. After excluding duplicate abstracts, 33 were selected. From these, two were eligible for quality assessment and were classified as being of moderate evidence. The included studies did not demonstrate association between AP and TNF-α -308 G>A SNP. However, the meta-analysis demonstrated an association between the genotype distribution and AP phenotype (OR= 0.49; confidence interval= 0.25, 0.96; p=0.04). The role of TNF-α -308 G>A SNP in AP phenotypes is debatable. Further studies are needed to confirm and understand the underlying mechanisms of the identified association.

Highlights

Apical periodontitis (AP) is generally a sequel of a root canal system infection, but even though microbial factors play a main role in the etiology of AP, the presence of lymphocytes, macrophages and neutrophils in periapical lesions indicates that the immune system is involved in the process of pathogenesis [1,2]
Focused Question The present systematic review was conducted in order to answer the following focused question: “Is there an association between TNF-α -308 G>A polymorphism and AP phenotype in the permanent teeth of humans?” The question was developed by using the patient population, exposition, comparison and outcome (PECO) framework
25 studies were excluded after reading the title and abstract due to obvious irrelevance towards the proposed theme; one study was excluded since it was a systematic review; five studies were excluded as they assessed associations between other genes and AP (e.g. CD14, TLR4, MMP2, MMP3, MMP9, MMP13, MMP14, TIMP2, IL-1, FcƔRIIIa, IL1-β;)

Summary

Introduction

Apical periodontitis (AP) is generally a sequel of a root canal system infection, but even though microbial factors play a main role in the etiology of AP, the presence of lymphocytes, macrophages and neutrophils in periapical lesions indicates that the immune system is involved in the process of pathogenesis [1,2]. The main immunological constituents of periapical lesions are represented by macrophages and type 1 T helper cells (Th1). Cytokines such as tumor necrosis factor alpha (TNF-α) and interleukins (1a, 1b, 6, 8 and 12p40) probably take part in the development of AP. TNF has many biological activities, has a direct cytotoxic effect and a general debilitating effect in chronic disease and plays an important role in immune response, causing severe damage to the host when the balance between pro- and anti- inflammatory cytokines is broken

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