Venkata Subbiah Harini, Ramesh Babu Polani, Subbiah Usha
Human Genetics Research Centre, Sree Balaji Dental College & Hospital, Bharath Institute of Higher Education and Research, Chennai, IND.
Center for Materials Engineering and Regenerative Medicine, Bharath Institute of Higher Education and Research, Chennai, IND.
Cureus. 2023 Dec 1;15(12):e49814. doi: 10.7759/cureus.49814. eCollection 2023 Dec.
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 ( 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 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 gene and susceptibility to periodontitis associated with type 2 diabetes mellitus (T2DM) and analyzed the effect of 5' UTR polymorphisms on gene expression Methods SNPs in the 5' UTR of the 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). 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. 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 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 gene may be an important predictive factor for periodontitis.
引言
牙周炎是一种由牙周病原菌引起的多因素疾病，受遗传和环境因素影响。研究发现遗传易感性在牙周病的发生和发展中起关键作用。糖尿病与牙周炎之间存在双向关系，糖尿病患者可见严重的牙周组织破坏。抗菌肽β-防御素-1（基因）在先天免疫反应中起重要作用，是宿主抵御牙周病原体的第一道防线。该基因特定遗传位点的单核苷酸多态性（SNP）及其表达水平可能赋予与糖尿病相关的牙周炎一定程度的风险或保护作用。本研究确定该基因5'非翻译区（UTR）的SNP与2型糖尿病（T2DM）相关牙周炎易感性之间的关联，并分析5'UTR多态性对该基因表达的影响。
方法
采用聚合酶链反应（PCR）及桑格测序法对该基因5'UTR（-20G>A（rs11362）、-44C>G（rs1800972）和-52G>A（rs1799946））的SNP进行基因分型。研究组包括牙周炎患者（n = 40）、伴T2DM的牙周炎患者（n = 20）以及牙周和全身健康的对照组（n = 40）。在包括牙周炎患者（n = 20）、伴T2DM的牙周炎患者（n = 15）和健康对照组（n = 20）的研究组中，通过实时PCR测定该基因的表达。采用统计工具分析5'UTR多态性对表达的影响。
结果
与健康对照组相比，在牙周炎患者（优势比（OR）= 3.64，95%置信区间（CI）= 1.16 - 11.43，p = 0.04）和伴T2DM的牙周炎患者中（OR = 5.14，95%CI = 1.29 - 20.5，p = 0.03），观察到rs11362的变异AA基因型患病率在统计学上显著更高。此外，与健康对照组相比，牙周炎患者中rs1799946的变异AA基因型显著增加（OR = 3.88，95%CI = 1.19 - 12.68，p = 0.04）。与健康对照组相比，牙周炎患者该基因表达下调，伴T2DM的牙周炎患者该基因表达上调，但差异无统计学意义。未发现该基因SNP对其表达的影响存在显著关联。
结论
从SNP分析可以推断，该基因5'UTR（rs11362和rs1799946）存在SNP可能是牙周炎的一个重要预测因素。
