Investigation of the association of genetic variation regarding susceptibility to chronic periodontal disease by OpenArray

• Grant number: 14/13295-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2014
• End date: March 31, 2018
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Raquel Mantuaneli Scarel Caminaga
• Grantee: Rafael Nepomuceno Oliveira
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated scholarship(s): 16/18313-3 - Investigation of genetic variations susceptibility to chronic periodontitis by OpenArray®: Biostatistics, Bioinformatics and Functional Analysis, BE.EP.DR

Abstract

Studies have reported that polymorphisms in genes, such as those encoding cytokines, may affect susceptibility to PD. To optimize the analysis of various single nucleotide (SNPs), high performance technologies, such as microarrays, have currently been employed. Although there are several studies focusing on the association of genetic polymorphisms with PD, further studies are still necessary because there were not identified polymorphisms that may be considered genetic markers of PD in the Brazilian population, beside the fact that many other genes with biological functions key (not just the immune system) were rarely or never studied. The objective of this study is to investigate SNPs in candidate genes in a Brazilian population composed of individuals with chronic periodontitis compared to healthy individuals, aiming to identify SNPs that may influence susceptibility to chronic PD. According to the sample size calculation, after detailed and complete periodontal examination, a total of at least 722 patients will be selected and divided into two groups according to the criteria defined by the CDC / AAP (Centers for Disease Control and Prevention / American Academy of Periodontology): (i) Group A (n = 361) patients with moderate or severe periodontitis; Group B (n = 361): patients with mild periodontitis and healthy patients. Each individual will undergo a mouth rinse with a glucose solution to be used for DNA extraction. For the selection of the SNPs, HAPLOVIEW program was used from the data bank of the International HapMap Project. 81 SNPs distributed among genes with Meta-analysis for PD, candidate genes from previous GWAS (Genome-Wide Association Study) or Bioinformatics studies, and genes related to the Th17 response and oxidative process will be investigated. Each SNP will be investigated through PCR reactions (Polymerase Chain Reaction) Real-Time, using the TaqMan® genotyping system OpenArrayTM (Applied Biosystems). The processing of data from genotyping and the calculation of allele frequencies (Minimum Frequency Allele - MAF) of the SNPs will be performed, as well as the Hardy-Weinberg equilibrium, and the degree of linkage disequilibrium between the SNPs. A multivariate logistic regression will be performed to adjust the results to variables such as age, gender and smoking habits, using the program R. The statistical results are corrected for multiple testing using the Bonferroni correction. It is expected that this work will have validation (or not) in our population of polymorphisms previously associated with PD, and novel results related to polymorphisms in our population not yet investigated. By detailed clinical examination and after robust statistical analysis, SNPs may be associated (or not) to the susceptibility and / or severity of PD. These results can effectively contribute to the quest of genetic markers for PD in our population. (AU)

Scientific publications

(9)

(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)

NEPOMUCENO, RAFAEL; PIGOSSI, SUZANE C.; FINOTI, LIVIA S.; ORRICO, SILVANA R. P.; CIRELLI, JONI A.; BARROS, SILVANA P.; OFFENBACHER, STEVEN; SCAREL-CAMINAGA, RAQUEL M.. Serum lipid levels in patients with periodontal disease: A meta-analysis and meta-regression. JOURNAL OF CLINICAL PERIODONTOLOGY, v. 44, n. 12, p. 1192-1207, DEC 2017. (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; 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)

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)

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)

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)

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)

Academic Publications

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

OLIVEIRA, Rafael Nepomuceno. Investigation of genetic polymorphisms and lipid metabolism with chronic periodontal disease: meta-analysis and case-control study. 2018. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Faculdade de Odontologia. Araraquara Araraquara.