Genetic Polymorphism and Gene Expression of β-Defensin-1 in Periodontitis Associated With Type 2 Diabetes Mellitus

Introduction Periodontitis is a multifactorial disease caused by periodontopathic bacteria and influenced by both genetic and environmental factors. Genetic predispositions are found to play a crucial part in the onset and progression of periodontal disease. There is a two-way relationship between diabetes and periodontitis with severe periodontal tissue destruction seen in diabetic patients. Antimicrobial peptide, β-defensin-1 (DEFB1 gene), plays an important role in the innate immune responses and forms the first line of host defense against periodontal pathogens. Single nucleotide polymorphisms (SNPs) in the specific genetic loci of the DEFB1 gene and its expression level could confer a degree of risk or protection from periodontitis associated with diabetes. The present study determined the association between SNPs at the 5' untranslated region (UTR) in the DEFB1 gene and susceptibility to periodontitis associated with type 2 diabetes mellitus (T2DM) and analyzed the effect of 5' UTR polymorphisms on DEFB1 gene expression. Methods SNPs in the 5' UTR of the DEFB1 gene (-20G>A (rs11362), -44C>G (rs1800972), and -52G>A (rs1799946)) were genotyped by polymerase chain reaction (PCR) followed by Sanger sequencing. The study group included periodontitis (n = 40), periodontitis with T2DM (n = 20), and periodontally and systemically healthy as controls (n = 40). DEFB1 gene expression was determined by real-time PCR in the study group comprising periodontitis (n = 20), periodontitis with T2DM (n = 15), and healthy controls (n = 20). The effect of 5' UTR polymorphisms on the expression was analyzed by statistical tools. Results Statistically significant higher prevalence of the variant AA genotype of rs11362 was observed in periodontitis (odds ratio (OR) = 3.64, 95% confidence Interval (CI) = 1.16-11.43, p = 0.04) and periodontitis with T2DM (OR = 5.14, 95% CI = 1.29-20.5, p = 0.03) in comparison with healthy controls. Moreover, there was a significant increase of the variant AA genotype of rs1799946 in periodontitis (OR = 3.88, 95% CI = 1.19-12.68, p = 0.04) compared to healthy controls. DEFB1 gene expression was downregulated in periodontitis and upregulated in periodontitis with T2DM patients when compared to healthy controls but was not statistically significant. No significant association was found for the effect of SNPs of the DEFB1 gene on its expression. Conclusion From the SNP analysis, it can be inferred that the presence of SNPs at the 5' UTR (rs11362 and rs1799946) in the DEFB1 gene may be an important predictive factor for periodontitis.