Investigation of genetic polymorphisms and lipid metabolism with chronic periodontal disease: meta-analysis and case-control study

Author(s)

Rafael Nepomuceno Oliveira

• Document type: Doctoral Thesis
• Press: Araraquara. 2018-05-04.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Odontologia. Araraquara
• Defense date: 2018-03-28
• Advisor: Raquel Mantuaneli Scarel Caminaga

Abstract

Several factors related to the host, such as environmental factors (smoking), systemic diseases (diabetes and dyslipidemia) and genetic inheritance have been studied regarding the influence on the onset and progression of periodontal disease. Although several studies have investigated the relationship between dyslipidemia and chronic periodontitis (CP), focusing on serum lipid levels, the results are still contradictory, indicating the necessity of a meta-analysis. Some genome-wide association studies (GWAS), bioinformatics studies and several case-control studies have shown genetic variants associated with susceptibility to CP, but the results of some of these polymorphisms are sparse and contradictory among different populations. Thus, it is important to conduct meta-analysis and case-control studies in order to validate or identify an association of polymorphisms with CP in a Brazilian population. The objective of this study was divided into three chapters: (1) to investigate whether patients with CP present different serum levels of lipid parameters (HDL, LDL, total cholesterol and triglycerides) compared to healthy individuals; (2) to assess whether single nucleotide polymorphisms (SNPs) in the LDLR (rs5925 and rs688) and APOB (rs676210 and rs693) genes contribute to CP susceptibility, since CP is associated with higher plasma LDL levels and the polymorphisms of these genes may increase plasma LDL concentration; (3) to validate, in the Brazilian population, the association of genetic polymorphisms previously associated with CP in other populations, through studies using sophisticated bioinformatics techniques and GWAS. A systematic review with meta- analysis and meta-regression was performed in chapter (1). Case-control studies with genotyping of SNPs in patients with and without CP were performed in chapters (2) and (3). These studies was conducted to investigate the association of different SNPs genotypes respecting to CP and periodontal parameters, as well as to evaluate sex-specific genetic association, and gene-environmental interaction. In the meta-analysis, 19 publications were included. It was found that participants with CP had significant higher LDL and triglycerides serum levels (p = 0.003 and p < 0.0001, respectively) and lower HDL levels (p = 0.0005) compared to healthy patients. As a result of chapter (2), no significant association was found between the periodontal clinical parameters and the frequencies of genotypes of any of the SNPs in the APOB and LDLR genes evaluated. Comparing patients with and without CP, there were no significant differences in any multivariate analysis, multiplicative and additive interactions between each SNP and smoking and haplotype frequency in the two genes. Regarding chapter (3), the rs2521634 (near the NPY gene) and rs3811046 (in the IL37 gene) SNPs were validated in the Brazilian population studied in association with CP. In conclusion, CP was associated with higher levels of LDL and triglycerides and lower levels of HDL; while it was not associated with the SNPs studied in the LDLR and APOB genes; but there was validation in the studied Brazilian population of the SNPs near to the NPY gene and in the IL37 gene with a higher risk association to severe and moderate CP, previously identified by the GWAS. (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