Polymorphism in epigenetic regulating genes in relation to periodontitis, number of teeth, and levels of high-sensitivity C-reactive protein and glycated hemoglobin: The Tromsø Study 2015-2016

Background: The aim of this study was to investigate the association between periodontitis and four single nucleotide polymorphisms (SNPs) in genes involved in epigenetic regulation of DNA, and between these same SNPs and tooth loss, high-sensitivity C-reactive protein (hs-CRP), and glycated hemoglobin (HbA1c) levels. Methods: We included participants with periodontal examination (n = 3633, aged: 40–93 years) from the Tromsø Study seventh survey (2015–2016), Norway. Periodontitis was defined according to the 2017 AAP/EFP classification system as no periodontitis, grades A, B, or C. Salivary DNA was extracted and genotyping was performed to investigate four SNPs (rs2288349, rs35474715, rs34023346, and rs10010325) in the sequence of the genes DNMT1, IDH2, TET1, and TET2. Association between SNPs and periodontitis was analyzed by logistic regression adjusted for age, sex, and smoking. Subgroup analyses on participants aged 40–49 years were performed. Results: In participants aged 40-49 years, homozygous carriage of minor A-allele of rs2288349 (DNMT1) was associated with decreased susceptibility to periodontitis (grade A: odds ratio [OR] 0.55; p = 0.014: grade B/C OR 0.48; p = 0.004). The minor A-allele of rs10010325 (TET2) was associated with increased susceptibility to periodontitis (grade A OR 1.69; p = 0.035: grade B/C OR 1.90; p = 0.014). In the entire sample, homozygous carriage of the G-allele of rs35474715 (IDH2) was associated with having ≤24 teeth (OR 1.31; p = 0.018). Homozygous carriage of the A-allele of TET2 was associated with hs-CRP≥3 mg/L (OR 1.37; p = 0.025) and HbA1c≥6.5% (OR 1.62; p = 0.028). Conclusions: In this Norwegian population, there were associations between polymorphism in genes related to DNA methylation and periodontitis, tooth loss, low-grade inflammation, and hyperglycemia.