Banca de QUALIFICAÇÃO: MARIA EDUARDA CARDOSO DE MELO

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : MARIA EDUARDA CARDOSO DE MELO
DATE: 22/11/2023
TIME: 08:00
LOCAL: Videoconferencia - Link para acesso: https://meet.google.com/ody-cret-yow
TITLE:

RELATIONSHIP BETWEEN ADIPONECTIN, OXIDATIVE STRESS, AND DNA REPAIR IN INDIVIDUALS WITH GENERALIZED CONGENITAL LIPODYSTROPHY TYPES 1 AND 2.

KEY WORDS:

Adipose tissue; Congenital Generalized Lipodystrophies; AGPAT2; Pathogenic variants; Adipose tissue-related diseases.

PAGES: 112
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Congenital Generalized Lipodystrophy (CGL) is a rare disease that causes the loss of adipose tissue (AT) throughout the body from birth. LGC patients have low levels of leptin and adiponectin (APN), important adipokines produced by AT. Hypertriglyceridemia, hyperinsulinemia and triglyceridemia are also metabolic findings in patients with CGL. There are 4 types of CGL, with types 1 and 2 being responsible for more than 80% of the analyses described in the literature and with patients already described in northeastern Brazil. The molecular etiology for LGC 1 is the presence of pathogenic variants (PVs) in the AGPAT2 gene. There is great genetic heterogeneity in the inheritance of PVs for this gene. Therefore, this study carried out a molecular analysis of the main VPs described for AGPAT2 (c.366-588del, c.589-2A>G, c.646A>T, c.570C>A, c.369-372delGCTC, c.202C>T, c.514G>A, c.144C>A) and an analysis of the effects on their transmembrane and functional domains. We also evaluated the genotype relationship of these variants and the phenotype of the first patients described in the literature for each one. In addition, we performed the molecular diagnosis of two sisters with VPs in compound heterozygosity for c.299G>A and c.493-1G>C and a new patient described for the c.366-588del variant. In addition, we used next-generation sequencing (NGS) to analyze a panel of genes associated with adipose tissue-related diseases in LGC patients. Another objective of this study was to compare leptin and APN levels between the LGC 1 and LGC 2 groups. As has already been shown in the literature, it was observed that patients with LGC type 2 have lower leptin levels when compared to those with type 1. However, unlike the studies already reported, we didn't observe any significant differences between the APN dosages of these two groups. In terms of the expression of enzymes involved in repairing oxidized DNA damage (APE-1, OGG1 and PPARG), no significant differences were observed between the LGC 1 and LGC 2 groups, although both types have higher levels of expression of these genes when compared to that observed in control individuals. This suggests that the different molecular etiology of the two types of LGC is not, in itself, a significant parameter for altering redox homeostasis between these two groups. More studies are needed to better understand the relationship between LGC and oxidative stress, DNA repair and cellular response.

COMMITTEE MEMBERS:
Presidente - 1046922 - LEONARDO CAPISTRANO FERREIRA
Externo ao Programa - 2220417 - CARLOS AUGUSTO GALVAO BARBOZA - UFRNExterno ao Programa - 1451614 - JOSIVAN GOMES DE LIMA - UFRN