Department of Diagnosis and Surgery, São Paulo State University - UNESP, School of Dentistry at Araraquara, Araraquara, SP, Brazil.
Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, São Paulo State University - UNESP, School of Dentistry at Araraquara, Araraquara, SP, Brazil.
Clin Oral Investig. 2021 Jun;25(6):3873-3892. doi: 10.1007/s00784-020-03717-3. Epub 2021 Jan 3.
Genome-wide association studies (GWAS) and literature have identified polymorphisms in the KCNJ11, HNF1A, IRS1, TCF7L2, CDKAL1, CDKN2B, RPSAP52, GPR45 HHEX, IL18, and RUNX2 genes associated with type 2 diabetes mellitus (T2DM) and/or periodontitis (P) in diverse populations, and we sought to evaluate them as genetic risk variants for these diseases in the Brazilian population.
Periodontal, glycemic, and lipid data were obtained from 931 individuals divided into: control (n = 334), periodontitis (P; n = 358), and periodontitis associated with T2DM (P + T2DM; n = 239). After genotyping, associations between polymorphisms and pathologies were tested by multiple logistic and linear regressions, adjusting for age, sex, and smoking habits.
Considering the studied subjects, the increased risk to develop periodontitis in the periodontitis P + T2DM group was found for HNF1A-rs7957197-TA, CDKAL1-rs7754840-CG, RPSAP52-rs1531343-GC, TCF7L2-rs7903146-TT, and CDKN2B-rs7018475-GG. The association of these genetic variants for TCF7L2 and CDKN2B was confirmed for female, never smokers, and poorly controlled P + T2DM. CDKN2B-rs7018475 was associated with worse glycemic condition and periodontal parameters.
These five reported genetic variants were associated in the studied Southeastern Brazilian population as genetic risk variants of periodontitis and T2DM associated to periodontitis as comorbidity. Gene-phenotype associations with sex and smoking habits and the CDKN2B-rs7018475 with the poor glycemic control and more severe periodontal conditions should be further investigated.
Polymorphisms in the CDKAL1-rs7754840, HNF1A-rs7957197, RPSAP52-rs1531343, TCF7L2-rs7903146, and CDKN2B-rs7018475 might predispose to periodontitis and T2DM associated with periodontitis. These findings may be useful in public health genomics and future advanced clinical practice, since genetic carriage can be measured before disease onset, being of potential great benefit for treatment planning and prognosis in early disease stages.
全基因组关联研究（GWAS）和文献已经确定了 KCNJ11、HNF1A、IRS1、TCF7L2、CDKAL1、CDKN2B、RPSAP52、GPR45 HHEX、IL18 和 RUNX2 基因中的多态性与 2 型糖尿病（T2DM）和/或牙周炎（P）在不同人群中有关，我们试图评估它们作为巴西人群中这些疾病的遗传风险变异。
从 931 名个体中获得牙周、血糖和血脂数据，这些个体分为：对照组（n=334）、牙周炎组（P；n=358）和牙周炎合并 T2DM 组（P+T2DM；n=239）。在进行基因分型后，通过多元逻辑和线性回归测试多态性与病理学之间的关联，同时调整年龄、性别和吸烟习惯。
考虑到所研究的受试者，在 P+T2DM 牙周炎组中，HNF1A-rs7957197-TA、CDKAL1-rs7754840-CG、RPSAP52-rs1531343-GC、TCF7L2-rs7903146-TT 和 CDKN2B-rs7018475-GG 的出现增加了发生牙周炎的风险。在女性、从不吸烟者和控制不佳的 P+T2DM 中，这些遗传变异与 TCF7L2 和 CDKN2B 的关联得到了确认。CDKN2B-rs7018475 与血糖状况和牙周参数较差有关。
在本研究的东南巴西人群中，这五个已报道的遗传变异被认为是牙周炎和与牙周炎相关的 T2DM 的遗传风险变异。与性别和吸烟习惯的基因表型关联以及 CDKN2B-rs7018475 与血糖控制不佳和更严重的牙周状况有关，应进一步研究。
CDKAL1-rs7754840、HNF1A-rs7957197、RPSAP52-rs1531343、TCF7L2-rs7903146 和 CDKN2B-rs7018475 中的多态性可能易患牙周炎和与牙周炎相关的 T2DM。这些发现可能对公共卫生基因组学和未来的高级临床实践有用，因为可以在疾病发作前测量遗传携带情况，这对疾病早期阶段的治疗计划和预后具有潜在的巨大益处。
