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

Author(s)

da Silva, Barbara Roque ^{[1, 2]} ; Cirelli, Thamiris ^{[1, 2]} ; Nepomuceno, Rafael ^{[1, 2]} ; Theodoro, Leticia Helena ^{[3, 4]} ; Orrico, Silvana R. P. ^{[1, 5]} ; Cirelli, Joni A. ^[1] ; Barros, Silvana P. ^[6] ; Scarel-Caminaga, Raquel M. ^[2]

Affiliation

^[1] Sao Paulo State Univ, Sch Dent Araraquara, Dept Diag & Surg, UNESP, Araraquara, SP - Brazil

^[2] Sao Paulo State Univ, Sch Dent Araraquara, Dept Morphol Genet Orthodont & Pediat Dent, UNESP, CP 331, BR-14801903 Araraquara, SP - Brazil

^[3] Sao Paulo State Univ, Sch Dent Aracatuba, Dept Surg, UNESP, Aracatuba, SP - Brazil

^[4] Sao Paulo State Univ, Sch Dent Aracatuba, Integrated Clin, UNESP, Aracatuba, SP - Brazil

^[5] Union Coll Great Lakes UNILAGO, Adv Res Ctr Med, BR-15030070 Sao Jose Do Rio Preto, SP - Brazil

^[6] Univ North Carolina Chapel Hill, Sch Dent, Dept Comprehens Oral Hlth Periodontol, UNC, Chapel Hill, NC - USA

• Document type: Journal article
• Source: DIABETES & METABOLIC SYNDROME-CLINICAL RESEARCH & REVIEWS; v. 14, n. 6, p. 1665-1672, NOV-DEC 2020.
• Web of Science Citations: 0

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 TaqMane. 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. (C) 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 14/13295-1 - Investigation of the association of genetic variation regarding susceptibility to chronic periodontal disease by OpenArray
• Grantee: Rafael Nepomuceno Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/03753-8 - Investigation of potential genetic markers of chronic periodontitis associated or not with type 2 diabetes mellitus through patient's genetic susceptibility and both glycemic and lipid profiles
• Grantee: Raquel Mantuaneli Scarel Caminaga
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/18313-3 - Investigation of genetic variations susceptibility to chronic periodontitis by OpenArray®: Biostatistics, Bioinformatics and Functional Analysis
• Grantee: Rafael Nepomuceno Oliveira
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 16/25418-6 - Investigation of the haplotype in the IL8 gene association with susceptibility to chronic periodontal disease and type 2 Diabetes Mellitus
• Grantee: Bárbara Roque da Silva
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 18/26367-1 - Investigation of polymorphs in the DEFB1 gene with susceptibility to chronic periodontal disease and type 2 diabetes mellitus
• Grantee: Ana Cláudia dos Santos Rios
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 16/08070-6 - Investigation of genetic susceptibility to chronic periodontitis associated with Type 2 Diabetes mellitus
• Grantee: Thamiris Cirelli
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)