Interaction between polymorphisms in TNF-⍺ and RANKL genes is associated with the development of persistent apical periodontitis, in Brazilian subjects

Objectives

To investigate the association between genetic polymorphisms in suppressor of cytokine signaling-1 (SOCS-1), tumor necrosis factor-⍺ (TNF-α) and its receptors 1 and 2 (TNFRSF1A and TNFRSF1B), receptor activator of nuclear factor kappa-b (RANK), receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin (OPG), and persistent apical periodontitis (PAP).

Methods

Patients with pulp necrosis and apical periodontitis at the time of non-surgical root canal treatment were followed up for at least one year. A total of 423 subjects were included, 172 with signs/symptoms of PAP and 251 with apical periodontitis healed. DNA was extracted from saliva and used for genotyping polymorphisms in SOCS1 (rs243327 and rs33977706), TNF-α (rs1800629), TNFRSF1A (rs1800693), TNFRSF1B (rs1061622), RANK (rs1805034), RANKL (rs1054016) and OPG (rs1032128) by real-time PCR. The frequency of genotypes and alleles was assessed using chi-squared test or Fisher's exact test and odds ratio. Interactions were also tested using multifactor dimensionality reduction (α = 5 %).

Results

In the polymorphism rs1800629 in TNF-α, carrying at least one A risk allele significantly decreased the risk to develop PAP (OR=0.47; 95 %CI: 0.28–0.79; p=0.004). For the polymorphism rs1054016 in RANKL carrying both T risk alleles significantly decreased the risk to develop PAP (OR=0.47; 95 %CI: 0.24–0.92; p=0.027). None of the other polymorphisms evaluated were associated with PAP (p>0.05). A strong interaction was observed among rs1800629, rs1061622 and rs1054016.

Conclusions

Genetic polymorphisms rs1800629 (TNF-α) and rs1054016 (RANKL) had a strong interaction and were associated with a lower risk to develop PAP.