Association of polymorphisms in TNF‐α, IL‐1β, GSTM and GSTT genes with apical periodontitis: is there a link with herpesviral infection?
Aleksandar Jakovljević, Nadja Nikolić, Jelena Čarkić, K. Beljic‐Ivanovic, Ivan Soldatović, Maja Miletić, Miroslav Andrić, Jelena Milašin
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.