INVESTIGATION OF GENETIC POLYMORPHISMS IN BMP2, BMP4, SMAD6, AND RUNX2 AND PERSISTENT APICAL PERIODONTITIS

Abstract INTRODUCTION This study aimed to evaluate the interplay among single nucleotide polymorphisms (SNPs) in the encoding genes BMP2, BMP4, SMAD6, and RUNX2 in persistent apical periodontitis (PAP). METHODS In this multicentric study, 272 patients diagnosed of pulp necrosis with apical periodontitis before the root canal therapy, who attended regular follow-up visits for at least one year were screened. Periapical radiographs and clinical aspects were evaluated and the participants were classified as PAP (n=110) or Repaired (n=162). Genomic DNA was used for the genotyping of the following SNPs: rs1005464 and rs235768 in BMP2, rs17563 in BMP4, rs2119261 and rs3934908 in SMAD6, and rs59983488 and rs1200425 in RUNX2. Chi-square test was used to compare genotype distributions between groups. The multifactor dimensionality reduction (MDR) method was applied to identify SNP-SNP interactions. The alpha for all the analysis was 5%. RESULTS The MDR suggested the rs235768 in BMP2 and rs59983488 in RUNX2 as the best SNP-SNP interaction model (CV=10/10; TBA=0.584; p=0.026), followed by rs17563 in BMP4 and rs2119261 in SMAD6 (CV= 10/10; TBA=0.580; p=0.031). In the rs235768 in BMP2 and rs59983488 in RUNX2 model, the high-risk genotype was TT+TT (OR=4.36, CI 95%=0.44–42.1). In model rs17563 in BMP4 and rs2119261 in SMAD6, GG+TT (OR=2.63, CI 95%= 0.71–11.9) was the high-risk genotype. CONCLUSION The interactions between rs235768 in BMP2 and rs59983488 in RUNX2 and between rs17563 in BMP4 and rs2119261 in SMAD6 are associated with PAP, suggesting that an interplay of these SNPs is involved in the higher risk of developing PAP.