Associação de polimorfismos HLA e haplogrupos mitocondriais com a periodontite em pacientes com diabetes tipo 1 de uma população miscigenada brasileira

Abstract

The objectives of this Thesis were to investigate the relationship between class II HLA alleles (Chapter 1) and mitochondrial DNA haplogroups (Chapter 2) with the severity and extent of periodontitis in patients with type 1 diabetes from a highly admixed Brazilian population. The central hypothesis was that certain HLA alleles and mtDNA haplogroups would be associated with more severe or generalized forms of periodontitis in this group. A cross-sectional study was conducted with 49 patients with type 1 diabetes. Demographic and diabetes history data were collected. Periodontal examination was performed to assess probing depth (PD), clinical attachment level (CAL), gingival bleeding index (GBI), and visible plaque index (VPI). Patients were categorized according to periodontitis severity (Stages I to IV) and its extent (localized or generalized). Peripheral blood samples were analyzed for two purposes: (1) determination of autosomal ancestry proportions (Native American, European, and African) and identification of HLA-DRB1*, HLA-DQA1*, and HLA-DQB1* alleles; and (2) identification of mitochondrial haplogroups to evaluate the matrilineal inheritance pattern. Odds ratios (ORs) and their respective 95% confidence intervals (95% CIs) were calculated to estimate the association between class II HLA alleles and periodontitis outcomes (Chapter 1). Relative risks (RRs) and 95% CIs were calculated to assess the association between mtDNA categories and periodontal outcomes (Chapter 2). A 5% significance level was adopted for all tests. Regarding HLA alleles, DRB1*03 (OR = 19.8; 95% CI = 1.14–346; P = 0.003) and DRB1*15 (OR = 41.2; 95% CI = 1.85–917; P < 0.001) were associated with an increased risk of generalized periodontitis. These same alleles were also associated with severe periodontitis (Stages III–IV): DRB1*03 (OR = 7.71; 95% CI = 1.68–35.5; P = 0.003) and DRB1*15 (OR = 21.2; 95% CI = 0.97–461; P = 0.005). With respect to mitochondrial DNA, significant associations with the severity and extent of periodontitis were observed: haplogroups D (RR = 5.62; 95% CI = 3.60–8.77; P < 0.001) and L0 (RR = 5.11; 95% CI = 3.77–7.73; P < 0.001) were associated with advanced stages of periodontitis (III and IV). Haplogroups C (RR = 3.41; 95% CI = 1.21–5.62; P = 0.020) and D (RR = 4.50; 95% CI = 1.43–14.08; P = 0.009) were associated with the generalized form of periodontitis. The findings of this study indicate that patients with type 1 diabetes from a highly admixed Brazilian population present genetic factors associated with increased periodontal impairment. Specifically, the HLA-DRB1*03 and HLADRB1* 15 alleles, as well as mitochondrial haplogroups D, L0, and C, are associated with more severe and generalized forms of periodontitis. These results reinforce the role of genetic inheritance in susceptibility to periodontal disease in this patient group.