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

• Grant number: 16/03753-8
• Support Opportunities: Regular Research Grants
• Duration: August 01, 2016 - July 31, 2019
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Raquel Mantuaneli Scarel Caminaga
• Grantee: Raquel Mantuaneli Scarel Caminaga
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated researchers: Patricia de Carvalho Mastroianni ; Silvana Regina Perez Orrico

Abstract

Although evidences show association of polymorphisms in cytokine genes with susceptibility to chronic periodontitis (CP), there are many genes (e.g metabolism) that may affect the pathogenesis of PC that have not yet been investigated. Therefore, further studies are needed to identify polymorphisms associated with periodontal disease (PD) which can be used as genetic markers of PD in our population. Additionally, it was identified by this research group through the Transcriptome, differentially expressed genes in patients affected by diabetes mellitus type 2 (DM2) and PC, compared to patients without type 2 diabetes with/ without PC. It is important to investigate whether these results can be associated with different frequency of polymorphic alleles in these genes; i.e. if the pathological phenotype of patients is related to their differential genetic carriage. Polymorphisms in genes encoding enzymes usually influence the metabolic profile of the patient, which may relate to their periodontal condition. The objective of this project is to investigate the genetic susceptibility to chronic periodontitis associated or not with Type 2 Diabetes Mellitus and exploring its possible relationship with glycemic and lipid profile of the patient; seeking the genetic markers of PD (potentially associated with comorbidities) in our population. For this, 64 polymorphisms in genes important in the pathogenesis of the mentioned conditions will be simultaneously investigated by OpenArray genotyping platform. To facilitate understanding, we divided this research project into two subprojects: 1) Investigation of the genetic susceptibility to chronic periodontitis; and 2) Investigation of the genetic susceptibility to chronic periodontitis associated with diabetes mellitus type 2. Both subprojects are in the process of recruitment of patients and sample collection, the first of which has the support of FAPESP (Bolsa PhD), and the second has samples collected during the development of Transcriptome (supported FAPESP). Therefore, this project is an important continuation of our research. Considering the sample size calculation, 960 patients will undergo a complete periodontal examination, as well as biochemical analysis of their glycemic and lipid profile. For subproject 1 patients will be divided into Group A (n = 356) patients with severe or moderate PC; and Group B (n = 356) patients with mild PC and periodontal health. For subproject 2, we will investigate 248 patients with DM2 and PC (DM2_PC Group); and to compare the results, patients in the subproject 1 will be considered: Group A (without DM2 with severe or moderate PC, and Group B (without DM2 with mild PC or periodontally healthy) In addition to the DM2 diagnosis by a physician, recent results of glycemic and lipid profile were also be considered that will be offered to all volunteers in this project. If a patient recruited for the subproject 1 show suspected DM2 after the glycemic profile results, he/she will be referred for medical treatment. The same will be done in relation to suspected dyslipidemia, since all patients will receive information on the results of its glycemic, lipid and periodontal profiles. After complete periodontal examination and the biochemical tests, it will be obtained saliva of each patient for DNA extraction. Each single base polymorphism (SNP) will be investigated by the OpenArray genotyping system. After genetic analysis through softwares as JINGLEFIX and HAPLOVIEW it will be performed multiple logistic regression analysis using the R program seeking to adjust the results to variables such as age, gender, smoking and biochemical profile, beyond the Bonferroni correction. It is expected by the detailed periodontal, clinical biochemical and genetic data, and after robust statistical analysis, identifying genetic markers of PD in our population. (AU)

Scientific publications

(7)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CIRELLI, THAMIRIS; NEPOMUCENO, RAFAEL; RIOS, ANA CLAUDIA S.; ORRICO, SILVANA R. P.; CIRELLI, JONI A.; THEODORO, LETICIA H.; BARROS, SILVANA P.; SCAREL-CAMINAGA, RAQUEL M.. Genetic polymorphisms in theInterleukins IL1B, IL4,andIL6are associated with concomitant periodontitis and type 2 diabetes mellitus in Brazilian patients. JOURNAL OF PERIODONTAL RESEARCH, v. 55, n. 6, JUL 2020. (14/13295-1, 16/18313-3, 16/03753-8, 16/08070-6)

CIRELLI, THAMIRIS; NEPOMUCENO, RAFAEL; GOVEIA, JESSICA MARINA; ORRICO, SILVANA R. P.; CIRELLI, JONI A.; THEODORO, LETICIA HELENA; BARROS, SILVANA P.; SCAREL-CAMINAGA, RAQUEL M.. Association of type 2 diabetes mellitus and periodontal disease susceptibility with genome-wide association-identified risk variants in a Southeastern Brazilian population. CLINICAL ORAL INVESTIGATIONS, v. 25, n. 6, JAN 2021. (18/26367-1, 14/13295-1, 16/18313-3, 16/08070-6, 16/03753-8)

CIRELLI, THAMIRIS; NICCHIO, INGRA G.; BUSSANELI, DIEGO G.; SILVA, BARBARA R.; NEPOMUCENO, RAFAEL; ORRICO, SILVANA R. P.; CIRELLI, JONI A.; THEODORO, LETICIA H.; BARROS, SILVANA P.; SCAREL-CAMINAGA, RAQUEL M.. Evidence Linking PPARG Genetic Variants with Periodontitis and Type 2 Diabetes Mellitus in a Brazilian Population. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 7, p. 17-pg., 2023-04-01. (16/08070-6, 16/03753-8, 14/13295-1, 16/18313-3, 18/26367-1)

CIRELLI, THAMIRIS; NEPOMUCENO, RAFAEL; RIOS, ANA CLAUDIA S.; ORRICO, SILVANA R. P.; CIRELLI, JONI A.; THEODORO, LETICIA H.; BARROS, SILVANA P.; SCAREL-CAMINAGA, RAQUEL M.. Genetic polymorphisms in theInterleukins IL1B, IL4,andIL6are associated with concomitant periodontitis and type 2 diabetes mellitus in Brazilian patients. JOURNAL OF PERIODONTAL RESEARCH, v. 55, n. 6, p. 13-pg., 2020-07-09. (16/08070-6, 14/13295-1, 16/03753-8, 16/18313-3)

DA SILVA, BARBARA ROQUE; CIRELLI, THAMIRIS; NEPOMUCENO, RAFAEL; THEODORO, LETICIA HELENA; ORRICO, SILVANA R. P.; CIRELLI, JONI A.; BARROS, SILVANA P.; SCAREL-CAMINAGA, RAQUEL M.. Functional haplotype in the Interleukin8 (CXCL8) gene is associated with type 2 Diabetes Mellitus and Periodontitis in Brazilian population. DIABETES & METABOLIC SYNDROME-CLINICAL RESEARCH & REVIEWS, v. 14, n. 6, p. 1665-1672, NOV-DEC 2020. (14/13295-1, 16/03753-8, 16/18313-3, 16/25418-6, 18/26367-1, 16/08070-6)

RIMACHI HIDALGO, MARCO A.; CIRELLI, THAMIRIS; DA SILVA, BARBARA ROQUE; NICCHIO, INGRA GAGNO; NEPOMUCENO, RAFAEL; ORRICO, SILVANA R. P.; CIRELLI, JONI A.; THEODORO, LETICIA HELENA; BARROS, SILVANA P.; SCAREL-CAMINAGA, RAQUEL M.. Polymorphisms and haplotypes in the Interleukin 17 Alfa gene: potential effect of smoking habits in the association with periodontitis and type 2 diabetes mellitus. MOLECULAR BIOLOGY REPORTS, v. 48, n. 2, FEB 2021. (18/26367-1, 16/03753-8, 16/08070-6, 16/18313-3, 14/13295-1)

CIRELLI, THAMIRIS; NEPOMUCENO, RAFAEL; ORRICO, SILVANA R. P.; ROSSA, JR., CARLOS; CIRELLI, JONI A.; NORTH, KARI E.; GRAFF, MARIAELISA; BARROS, SILVANA P.; SCAREL-CAMINAGA, RAQUEL M.. Validation in a Brazilian population of gene markers of periodontitis previously investigated by GWAS and bioinformatic studies. Journal of Periodontology, v. 92, n. 5, p. 689-703, MAY 2021. (16/03753-8, 16/18313-3, 14/13295-1)