Banca de QUALIFICAÇÃO: VICTOR HUGO REZENDE DUARTE

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : VICTOR HUGO REZENDE DUARTE
DATE: 27/11/2020
TIME: 09:00
LOCAL: REMOTA (ONLINE
TITLE:

A DEFINIR

KEY WORDS:

Cardiovascular diseases, Subclinical atherosclerosis, Biomarkers, mRNA, miRNA and Polymorphisms.

PAGES: 147
BIG AREA: Ciências da Saúde
AREA: Medicina
SUMMARY:

Atherosclerosis is the main etiological factor for Coronary Artery Disease (CAD), and it remains asymptomatic for many years. Subclinical atherosclerosis (AS) is defined as the presence of any atherosclerotic plaque in the carotid, aortic or iliofemoral territory or the presence of coronary artery calcification. Considering the multifactorial nature of the development of CAD, and the difficulty in making its early diagnosis, this study sought to investigate the role of the TREML4 gene in the development of atherosclerotic lesions by genotyping of two main variants associated with this gene (rs2803495 and rs2803496), differential analysis of mRNA expression and identification of its regulatory miRNAs, according to an invivo and in-silico approach in AS patients. 329 patients with AS were recruited. Of these,132 were used to analyze the associations of the Duke score and 293 with DM2. The results with 132 AS patients stratified according to the Duke score demonstrated an association of the Duke score with increased expression of mRNA of the TREML4 in peripheral blood leukocytes (OR. = 3.173, 95% CI = 1.29-7, 78, p = 0.012). Furthermore, genotyping revealed that the SNP genotype combination rs2803495 (AG + GG) (OR = 9,007, 95% CI = 4.1-19.8, p <0.001) and rs2803496 (CT + CC) ( OR = 11.1, 95% CI = 4.8-25.4, p = 0.011), favor the expression of TREML4 mRNA. Subsequently, 293 people with AS stratified by the presence of type 2 Diabetes Mellitus were analyzed. The results showed that patients with AS and carriers of the SNP G alleles rs2803495 (AG + GG) (OR = 13.31, 95% CI = 5, 79-30.61, p <0.001) and C allele rs2803496 (CT + CC) (OR = 18.99, 95% CI = 7.60-47.44, p <0.001) are more likely to express TREML4. Once again, the C allele was associated with higher levels of mRNA expression (OR = 3.98, 95% CI = 1.67-9.48, p = 0.002). The rs2803495 (AG + GG) and rs2803496 (CT + CC) variants were not related to the development of DM2 (p> 0.05). However, patients who express TREML4 and are DM2 have higher levels of expression of TREML4 when compared to the control group (OR = 2.6, 95% CI = 1.19–5.72, p <0.001). Patients with DM2 and rs2803495 (AG + GG) genotypes are more likely to express TREML4 (OR = 20.77, 95% CI = 2.29- 188.41, p = 0.007). In silico analyzes showed that 8 miRNAs (hsa-miR-181a-5p, hsa-miR-200b-3p, hsa-miR-24-3p, hsa-miR-296-5p, hsa-miR-361-5p, hsa-miR423-5p, hsa-miR-486-3p and hsa-miR-708-5p) are expected to interact with TREML4 mRNA.Thus, the results suggest that mRNA expression of the TREML4 gene is associated with the presence of polymorphisms and increased in patients with AS with DM2 and that miRNAs may be involved in the regulation of the TREML4 gene being directly or indirectly involved in the pathophysiology of CVD being potential circulating biomarkers for early detection and/or individualized treatment of AS and CAD

BANKING MEMBERS:
Externa à Instituição - ADRIANA BERTOLAMI
Presidente - 1545315 - GUILHERME AUGUSTO DE FREITAS FREGONEZI
Externa à Instituição - Gisele Medeiros Bastos