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

Abstract

Aim To investigate the possible association between TNFα (−308 G/A) and IL‐1β (−511 C/T) single nucleotide polymorphisms (SNPs) and GSTT and GSTM deletion polymorphisms and risk of apical periodontitis (AP) development, and determine the association of different genotypes with the presence of herpesviral infection in AP. Methodology The study included 120 periapical lesions and 200 control samples. Gene polymorphism analysis was performed using either polymerase chain reaction (PCR) or PCR/ restriction fragment length polymorphism (RFLP). Relative gene expression of TNF‐α and IL‐1β was analysed using reverse transcriptase – real‐time PCR. The presence of Epstein–Barr virus (EBV) and human cytomegalovirus (HCMV) was assessed by nested PCR. Chi‐square and Fisher’s exact tests and logistic regression analyses were done for polymorphisms, whilst Mann–Whitney U‐test was performed for the expression analysis. The expected frequency of variants was analysed by the Hardy–Weinberg equilibrium test. Results TNF‐α (−308 G/A) SNP increased AP susceptibility for heterozygous (odds ratio (OR) = 1.72, 95% confidence interval (CI) = 1.06–2.80, P = 0.027) and homozygous (OR = 8.55, 95% CI = 1.77–41.36, P < 0.001) carriers of the variant A allele. On the other hand, IL‐1β (−511 C/T) polymorphism exerted a protective effect both in heterozygotes (OR = 0.540, 95% CI = 0.332–0.880, P = 0.013) and homozygotes (OR = 0.114, 95% CI = 0.026–0.501, P < 0.001). In addition, GSTM1 and GSTT1 null genotypes separately, as well as concomitantly, were associated with an increased risk for AP development (P < 0.001). The null GSTT1 genotype increased approximately twice the risk of Epstein–Barr infection (EBV) in AP (OR = 2.17, 95% CI = 1–4.71, P = 0.048), whilst TNF‐α SNP decreased it, both in heterozygotes (OR = 0.20, 95% CI = 0.08–0.48, P < 0.001) and AA homozygotes (OR = 0.07, 95% CI = 0.01–0.37, P = 0.001). Conclusions GSTM and GSTT deletion polymorphisms, as well as TNFα (−308 G/A) SNP, are associated with increased risk, whereas IL‐1β (−511 C/T) polymorphism decreases the risk of AP development. GSTT and TNFα polymorphisms also appear to modulate the risk of EBV infection in Serbian patients with AP.

Impact of root canal treatment on high‐sensitivity C‐reactive protein levels in systemically healthy adults with apical periodontitis – a preliminary prospective, longitudinal interventional study

“…2018) and genetic factors involved in the immune response which can delay periapical healing (Jakovljevic et al . 2020) could not be controlled in this study. However, intervention by root canal treatment and reduction of PAI scores in the present study were associated with significant reductions in the serum hsCRP levels and the null hypothesis was rejected.…”

Inflammasomes in Alveolar Bone Loss

“…Enterococcus faecalis and P. gingivalis are commonly detected pathogens in infected root canals and apical root surfaces of periapical periodontitis, respectively ( 183 , 262 ). IL-1β may play vital roles in bone loss in periapical periodontitis: IL1B gene polymorphisms are involved in the risk of periapical periodontitis development ( 263 ); IL-1β production is increased in periapical periodontitis in vivo ( 264 ); and IL-1β levels and osteoclast differentiation are upregulated in an in vitro coculture system of osteoblasts and osteoclasts ( 186 ). However, the roles of IL-18 in the pathogenesis and development of periapical periodontitis remain unclear.…”

Association between cardiovascular diseases and apical periodontitis: an umbrella review

“…2018, Jakovljevic et al . 2020) respectively. In this context, polymorphisms of gene encoding molecules implicated in the immune response may increase the predisposition to CVDs and at the same time, increase the susceptibility of the affected individuals to AP or delay the repair of periapical pathosis.…”