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

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 metaanalysis 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.

Association of polymorphisms in TNF‐α, IL‐1β, GSTM and GSTT genes with apical periodontitis: is there a link with herpesviral infection?

“…This is in contrast with some studies where no association was established between this SNP and the development of AP (de Sá et al 2007, Amaya et al 2013, Dill et al 2015). However, Salles et al (2017) have reported the association between TNF‐α (−308 G >A) polymorphism and acute AP. The present results are also in line with previously conducted studies in Serbian populations regarding functional polymorphisms in TNF‐α gene and the risk of peri‐implantitis (Rakic et al 2015) and odontogenic keratocystic tumour (Ilic et al 2017) development, both suggesting that homozygous carriers of the variant A allele are significantly more prone to disease development.…”

“…Genetic polymorphisms may be considered as disease modifiers in AP, affecting its severity and clinical course (Aminoshariae & Kulild 2015, Salles et al 2017, 2018, Küchler et al 2018). It is also reasonable to assume that individuals are not equally prone to the development of AP.…”

“…This mostly refers to functional polymorphisms that alter the quantity or the structure of the encoded proteins and, therefore, presumably modulate an individual’s susceptibility to AP (Küchler et al 2018). Thus far, three systematic reviews have provided a summary of the association studies on interleukin gene polymorphisms in AP (Aminoshariae & Kulild 2015, Salles et al 2017, 2018). In their study, Salles et al (2017) concluded that there was no association between TNFα (−308 G/A) and risk of AP development, but they found a weak association between the SNP and AP phenotype (acute/chronic).…”

“…Thus far, three systematic reviews have provided a summary of the association studies on interleukin gene polymorphisms in AP (Aminoshariae & Kulild 2015, Salles et al 2017, 2018). In their study, Salles et al (2017) concluded that there was no association between TNFα (−308 G/A) and risk of AP development, but they found a weak association between the SNP and AP phenotype (acute/chronic). On the other hand, they established, in another meta‐analysis (Salles et al 2018), that IL1β (+3954 C/T) polymorphism was associated with post‐treatment AP.…”

Current trends of genetics in apical periodontitis research

“…Furthermore, this review identified the absence of proper replication of genetic association studies in different populations. Although replications are considered a key part of genetic epidemiological research, only few research groups aimed to replicate previous studies with results compiled in two meta-analyses, 35,36 which report an association between the genetic polymorphism -308 G>A in TNF-α with acute AP and the polymorphism +3954 C>T in IL1B with persistent AP.…”