Functional haplotype in the Interleukin8 (CXCL8) gene is associated with type 2 Diabetes Mellitus and Periodontitis in Brazilian population. Issue 6 (November 2020)

• Record Type: Journal Article
• Authors: Silva, Bárbara Roque da; Cirelli, Thamiris; Nepomuceno, Rafael; Theodoro, Letícia Helena; Orrico, Silvana R.P.; Cirelli, Joni A.; Barros, Silvana P.; Scarel-Caminaga, Raquel M.
• Is Part Of: Diabetes & metabolic syndrome. Volume 14:Issue 6(2020)
• Page Start: 1665
• Page End: 1672
• Publication Date: 2020-11
• Subjects: Interleukin -- Genetic polymorphisms -- Periodontitis -- Diabetes mellitus -- Haplotypes; Diabetes -- Periodicals; Metabolism -- Disorders -- Periodicals; Diabetes Mellitus -- Periodicals; Metabolic Diseases -- Periodicals; Diabète -- Périodiques; Métabolisme, Troubles du -- Périodiques; Endocrinologie -- Périodiques; Diabète -- Physiopathologie -- Périodiques; Diabetes; Metabolism -- Disorders; Electronic journals; Periodicals; 616.462
• DOI: 10.1016/j.dsx.2020.08.036
• Languages: English
• ISSNs: 1871-4021

Abstract

Abstract: Background and aim: 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. Methods: 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. Results: 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). Conclusions: 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. Highlights: Heterozygous rs4073, rs2227307 and rs2227306 show a protective effect for diseased phenotypes. The TTC/TTC haplotype in the Interleukin 8 gene indicates susceptibility to Periodontitis. The TTC/TTC haplotype in the Interleukin 8 gene increases the risk of T2DM and Periodontitis.