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.
Department of Surgery and Integrated Clinic, São Paulo State University - UNESP, School of Dentistry at Araçatuba, Araçatuba, SP, Brazil.
Diabetes Metab Syndr. 2020 Nov-Dec;14(6):1665-1672. doi: 10.1016/j.dsx.2020.08.036. Epub 2020 Aug 31.
Type 2 Diabetes Mellitus (T2DM) and Periodontitis (P) are prevalent multifactorial disorders worldwide, sharing a bidirectional relationship influenced by the genetic susceptibility of the host immune system. We investigated whether SNPs in the Interleukin 8 (IL8, alias CXCL8) gene could be associated with T2DM and Periodontitis.
Genomic DNA was obtained from 874 Brazilian individuals divided into: Healthy group (n = 307), Periodontitis group (n = 334), and individuals affected by both T2DM and Periodontitis (T2DM_P) group (n = 233). The SNPs -251(T>A) rs4073, +396(T>G) rs2227307 and +781(C>T) rs2227306 were genotyped by TaqMan®. Multiple logistic regressions were used to determine the degree of association between polymorphisms (and haplotypes) with periodontitis and T2DM adjusted for known confounders.
The additive model revealed that the heterozygous AT(-251), GT(+396) and CT(+781) genotypes showed a lower risk for the diseased phenotypes, and carriers of the TTC/TTC haplotype were significantly susceptible to T2DM and Periodontitis concomitantly, as well to isolated Periodontitis (mainly the severe form).
We concluded, for the first time, that these functional CXCL8 SNPs, and the homozygous TTC haplotype are relevant genetic factors for T2DM and Periodontitis as comorbidities, as well as for severe Periodontitis susceptibility in Brazilian population.
2 型糖尿病（T2DM）和牙周炎（P）是全球普遍存在的多因素疾病，它们之间存在双向关系，受宿主免疫系统的遗传易感性影响。我们研究了白细胞介素 8（IL8，别名 CXCL8）基因中的 SNP 是否与 T2DM 和牙周炎相关。
从 874 名巴西个体中获得基因组 DNA，这些个体分为：健康组（n=307）、牙周炎组（n=334）和同时患有 T2DM 和牙周炎的个体组（T2DM_P 组，n=233）。采用 TaqMan®技术对 SNPs-251（T>A）rs4073、+396（T>G）rs2227307 和+781（C>T）rs2227306 进行基因分型。采用多因素逻辑回归分析来确定多态性（和单倍型）与牙周炎和 T2DM 之间的关联程度，同时调整已知的混杂因素。
加性模型显示，杂合 AT（-251）、GT（+396）和 CT（+781）基因型患疾病表型的风险较低，并且 TTC/TTC 单倍型携带者同时易患 T2DM 和牙周炎，以及单纯牙周炎（主要是严重形式）。
我们首次得出结论，这些功能性 CXCL8 SNPs 以及纯合 TTC 单倍型是 T2DM 和牙周炎作为共病的相关遗传因素，也是巴西人群中严重牙周炎易感性的相关遗传因素。
