Investigation of genetic susceptibility to chronic periodontitis associated with Type 2 Diabetes mellitus

• Grant number: 16/08070-6
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2016
• End date: September 24, 2020
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Raquel Mantuaneli Scarel Caminaga
• Grantee: Thamiris Cirelli
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Although evidences have showed association of polymorphisms in cytokine genes with susceptibility to Chronic Periodontitis (CP), there are many genes, as metabolism genes, that may affect the etiopathogeny of CP but they has not been investigated yet. Therefore, further studies are necessary to identify polymorphisms that are associated with Periodontal Disease (PD) in order to be used as genetic markers of PD in our population. Additionally, it was identified by the present research group through the transcriptome, differentially expressed genes in patients affected by Type 2 Diabetes Mellitus (DM2) and CP, compared to patients without DM2 with and without CP. It is required 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 load. Polymorphisms in genes that codify enzymes used to influence the metabolic profile of the patients, which may relate to their periodontal condition. The objective of this study is to investigate the genetic susceptibility to chronic periodontitis associated with Type 2 Diabetes Mellitus and exploring its possible relation to glycemic and lipid profiles of the patient; in this sense, searching for genetic markers of PD (potentially associated with comorbidities) in our population. In this regard, 64 polymorphisms in important genes in the etiopathogeny of the mentioned pathologies will be simultaneously investigated by the genotyping platform openarray. This study is an important inter-relation between two research lines of our laboratory that investigates the DM2 associated with PD and genetic susceptibility to CP. Considering the sample calculation, 960 patients will be submitted to a complete periodontal examination, as well as a biochemical analysis of their glycemic and lipid profiles through laboratory tests. Patients will be investigated with DM2 and CP (Group DM2_CP, n = 248 patients); and to compare the results will be considered patients without DM2 (normoglycemic) with severe or moderate CP (Normo_CP group, n = 356), and also normoglycemic patients without CP, or periodontally healthy (Normo_CP group, n = 356). Therefore, the Normo_CP group will control the DM2 and Normo_CP group will control T2DM and CP. Besides the DM2 diagnosis by a physician, it will also be considered recent results of glycemic and lipid profiles that will be offered to all the volunteers in this project. All the patients will be informed of the results of their blood glucose, lipid and periodontal profiles, benefiting each project participant. After complete periodontal examination and the biochemical tests, saliva will be obtained from each patient for DNA extraction. Each Single Base Polymorphism (SNP) will be investigated through openarray genotyping system. After genetic analysis using software such as JINGLEFIX and HAPLOVIEW, multiple logistic regression analysis will be conducted using the R program in an attempt to adjust the results to variables such as age, gender, smoking and biochemical profiles in addition to the Bonferroni correction. Considering the detailed clinical periodontal, biochemical and genetic data and after robust statistical analysis, it is expected to identify genetic markers of PD in our population related to comorbidities such as DM2. (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)

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)

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)

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)

SILVA, ARLES NAISA AMARAL; NICCHIO, INGRA GAGNO; DA SILVA, BARBARA ROQUE; MARTELLI, MAURICIO GANDINI GIANI; HIDALGO, MARCO A. RIMACHI; NEPOMUCENO, RAFAEL; THEODORO, LETICIA H.; CIRELLI, JONI A.; ORRICO, SILVANA R. P.; CIRELLI, THAMIRIS; et al. Polymorphisms in risk genes of type 2 diabetes mellitus could be also markers of susceptibility to periodontitis. ARCHIVES OF ORAL BIOLOGY, v. 143, p. 12-pg., 2022-09-01. (16/18313-3, 16/08070-6, 14/13295-1)

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)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

CIRELLI, Thamiris. Investigation of genetic susceptibility to chronic periodontitis associated with type 2 diabetes mellitus. 2020. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Faculdade de Odontologia. Araraquara Araraquara.