Department of Diagnosis and Surgery, São Paulo State University-UNESP, School of Dentistry at Araraquara, Araraquara, Brazil.
Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, São Paulo State University-UNESP, School of Dentistry at Araraquara, Araraquara, Brazil.
J Periodontal Res. 2020 Dec;55(6):918-930. doi: 10.1111/jre.12784. Epub 2020 Jul 9.
To assess whether single nucleotide polymorphisms (SNPs) in the IL10, IL1A, IL1B, IL4, TNFA, IL6, OPG, RANK, and RANKL genes, "classically" related with periodontitis, could be associated with susceptibility to T2DM, and also with both diseases concomitantly.
There are common pathogenic mechanisms in type 2 diabetes mellitus (T2DM) and periodontitis, but the knowledge of the genetic aspect of this is limited. In patients affected by concomitant T2DM and periodontitis, whose incidence is increasing, there is scarce information regarding the gene-phenotype association, including whether there are genes able to influence both diseases as comorbidities.
Periodontal clinical parameters and biochemical profile (Insulin, Fasting Glycemia, HbA1c, Triglycerides, Total Cholesterol, HDL-cholesterol, and LDL-cholesterol) data were obtained from 894 individuals divided into following three groups: Healthy (H; n = 347), Periodontitis (P; n = 348), and Periodontitis + T2DM (P + T2DM; n = 199). DNA from oral epithelial cells was collected for genotyping. Associations between SNPs and pathologies were tested by multiple logistic regression models, adjusting for age, sex, and smoking habits. We also investigated whether there are sex or smoking effects of each SNP in these phenotypes.
The rs1143634-GA (IL1B) SNP showed significantly less likely to develop P + T2DM for all population and mainly for women (adjusted OR = 0.37, 95% CI = 0.16-0.88), while women carrying the rs224320 CT (IL4) were more susceptible to develop P + T2DM (adjusted OR = 1.81, 95% CI = 1.04-3.15). Men carrying the rs1800795-CC (IL6) genotype were less likely to develop T2DM (adjusted OR = 0.12, 95% CI = 0.02-0.70, P = .01).
Some SNPs in the IL1B, IL4, and IL6 genes demonstrated sex-influenced association with concomitant periodontitis and T2DM, increasing the evidence of a common genetic component between these diseases and contributing with the understanding of their common pathogenic mechanisms.
评估白细胞介素 10（IL10）、白细胞介素 1A（IL1A）、白细胞介素 1B（IL1B）、白细胞介素 4（IL4）、肿瘤坏死因子（TNFA）、白细胞介素 6（IL6）、骨保护素（OPG）、核因子-κB 受体活化因子配体（RANKL）和核因子-κB 受体活化因子（RANK）基因中的单核苷酸多态性（SNPs）是否与 2 型糖尿病（T2DM）的易感性相关，以及是否与这两种疾病同时相关。
2 型糖尿病（T2DM）和牙周炎之间存在共同的发病机制，但对其遗传方面的认识有限。在同时患有 T2DM 和牙周炎的患者中，发病率正在增加，关于基因表型相关性的信息很少，包括是否存在能够影响两种疾病作为合并症的基因。
从 894 名个体中获得牙周临床参数和生化特征（胰岛素、空腹血糖、HbA1c、甘油三酯、总胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇）数据，这些个体分为以下三组：健康组（H；n=347）、牙周炎组（P；n=348）和牙周炎合并 T2DM 组（P+T2DM；n=199）。从口腔上皮细胞中提取 DNA 进行基因分型。通过多因素逻辑回归模型，调整年龄、性别和吸烟习惯，检测 SNP 与疾病之间的关联。我们还研究了每个 SNP 在这些表型中是否存在性别或吸烟的影响。
rs1143634-GA（IL1B）SNP 在所有人群中，尤其是女性中，发生 P+T2DM 的可能性显著降低（调整后的 OR=0.37，95%CI=0.16-0.88），而携带 rs224320 CT（IL4）的女性更容易发生 P+T2DM（调整后的 OR=1.81，95%CI=1.04-3.15）。携带 rs1800795-CC（IL6）基因型的男性发生 T2DM 的可能性较低（调整后的 OR=0.12，95%CI=0.02-0.70，P=0.01）。
白细胞介素 1B、IL4 和 IL6 基因中的一些 SNP 表现出与同时发生的牙周炎和 T2DM 的性别相关联，增加了这些疾病之间存在共同遗传成分的证据，并有助于理解它们共同的发病机制。
