SEMINÁRIO DE QUALIFICAÇÃO (Doutorado) – Mateus Sousa de Almeida

23 de outubro de 2024 (quarta-feira) 12h

SEMINÁRIO DE QUALIFICAÇÃO (Doutorado)

MATEUS SOUSA DE ALMEIDA

Associação de polimorfismos de PECAM–1 e ICAM–1 com a Doença Arterial Coronariana em uma população do Rio Grande do Sul

Orientador: Dr. José Artur Bogo Chies

Banca Examinadora: Dra. Lavínia Schüler Faccini e Dra. Eliane Bandinelli

23 de outubro de 2024 (quarta-feira)

12h

Presencial: Anfiteatro do Departamento de Genética da UFRGS (Campus do Vale, prédio 43312)

Abstract

Coronary artery disease (CAD) is the leading cause of death and disability-adjusted life years (DALYs) worldwide. It is characterized by the accumulation of atherosclerotic plaques in epicardial arteries, driven by low-density lipoprotein (LDL) deposition in the vascular endothelium. Risk factors include smoking, hyperlipidemia, hypertension, diabetes, and aging. Inflammatory conditions increase the expression of adhesion molecules such as ICAM-1 and PECAM-1, promoting leukocyte adhesion and vascular inflammation. ICAM-1 encodes a glycoprotein involved in cell-cell adhesion, with dysfunction linked to atherosclerosis. Its expression is modulated by nitric oxide (NO) through endothelial nitric oxide synthase (eNOS), which reduces leukocyte adhesion under shear stress. PECAM-1 regulates leukocyte transmigration and vascular function, and polymorphisms in these genes can influence CAD susceptibility. This study explores the association between ICAM-1 and PECAM-1 polymorphisms and CAD in a population from southern Brazil. We analyzed DNA from individuals of European descent living in Porto Alegre and Campo Bom, Rio Grande do Sul. CAD patients (n = 234, 31-84 years, mean 60.2 ± 11.1) were diagnosed by coronary angiography at Hospital de Clínicas de Porto Alegre. Controls (n = 204, 40-83 years, mean 56.6 ± 10.3) had no cardiovascular disease or family history of such conditions. Genotyping of PECAM-1 53G>A and 373C>G polymorphisms was performed via PCR-RFLP. The ICAM-1 -1548A>G polymorphism was also analyzed using similar methods. Statistical tests included Hardy-Weinberg equilibrium, chi-square tests for categorical variables, and Student’s t-test for continuous variables (p < 0.05). There were no significant differences in body mass index (BMI) between groups (cases: 28.0 ± 4.67; controls: 28.18 ± 5.24). However, smoking (54.7% vs. 26.3%) and hypertension (64.5% vs. 17.7%) were more prevalent among CAD patients. Sedentary behavior was also significantly higher in CAD patients (65.8%) compared to controls (31.2%). Men were overrepresented in the CAD group (59% vs. 43.6%), and CAD patients were, on average, older than controls (60.2 ± 11.1 vs. 56.6 ± 10.3 years). The ICAM-1 -1548A>G polymorphism showed no significant association with CAD. For PECAM-1, the 53G>A polymorphism had a higher frequency of the G/A genotype in CAD cases (13%) than controls (5%), suggesting a heterozygote effect. The 373C>G polymorphism was associated with increased CAD risk, with the C/C genotype more frequent in cases (21%) than in controls (4.6%). This study highlights the role of PECAM-1 polymorphisms in CAD susceptibility, particularly the C/C genotype of 373C>G. While no association was found for ICAM-1, the findings emphasize the importance of considering genetic, behavioral, and environmental factors in cardiovascular risk assessments, CAD management and patient outcomes.