Banca de DEFESA: SUELLEN PINHEIRO CARVALHO

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : SUELLEN PINHEIRO CARVALHO
DATA : 27/10/2021
HORA: 09:00
LOCAL: IGM Sala Virtual 5
TÍTULO:

Genetic biomarkers of endothelial dysfunction in sickle cell disease: association with clinical and laboratory profiles

PALAVRAS-CHAVES:

sickle cell anemia, SC hemoglobinopathy, laboratory parameters, clinical manifestations, p-seletin, CD40, polymorphisms; haplotypes.

PÁGINAS: 200
GRANDE ÁREA: Ciências Biológicas
ÁREA: Biologia Geral
RESUMO:

INTRODUCTION: Sickle cell disease (SCD) is a group of hemoglobinopathies and
sickle cell anemia (SCA), characterized by HbSS homozygous, is the most severe form,
while SC hemoglobinopathy is milder. The main clinical manifestations in SCD results
from continuous hemolysis and the chronic inflammatory process, leading to anemia
and vaso-occlusion process. The vaso-occlusive crises have been associated with the
presence of sickle cell, reticulocytes, leukocytes and activated platelets, which alters the
vascular endothelium and enhancer blood hypercoagulability. Several genetic factors
have been associated with the clinical profile variability in SCD. OBJECTIVE:
identify genetic biomarkers of endothelial dysfunction and associations with laboratory
parameters and clinical manifestations in individuals with SCA and SC disease
METHODS: a cross-sectional study it was carried, whose clinical data were collected
using a standardized questionnaire (self-reported or reported by the parents);
hematological and biochemical analyzes were performed by automated methods;
molecular analyzes were performed to determine the βS haplotypes, α-thalassemia and
polymorphisms in SELP (rs6127, rs6131 and rs6136); SELPLG (rs2228315); CD40
(rs1883832); and CD40L (rs3092952); patients are followed-up at the Bahia
Hemotherapy and Hematology Foundation (HEMOBA). RESULTS: the first
manuscript involved 80 individuals with SCA and 51 individuals with HbSC, whose
laboratory parameters and clinical manifestations were compared. It was observed that
SCA patients exhibited a more prominent anemia, hemolysis, leukocytosis and
inflammation, and that HbSC patients had altered lipid markers. The main cause of
hospitalization in both groups was pain crises, which were associated with high red
blood cell counts in patients with SCA. The occurrence of dactylitis was significantly
higher in SCA patients and was associated with increased RDW, monocytes and CRP,
as well as with hydroxyurea therapy. Pneumonia and ACS were associated with high
CRP and LDL-C levels, respectively. In individuals with HbSC disease, a previous
history of splenomegaly was associated with reduction on platelet counts. The second
manuscript involved 80 patients with SCA and investigated the association of clinical
manifestations and laboratory parameters with the rs6127, rs6131 and rs6136
polymorphisms in the SELP gene; the rs2228315 polymorphism in the SELPLG gene;
rs1883832 in CD40 gene; and rs3092952 in CD40L gene. It was possible to identify an
association of the variant (rs3092952) CD40L gene with a previous history of painful
crises and dactylitis in SCA patients. Furthermore, our results suggest an independent
association of the variant (rs6127) SELP with increased ET-1 levels and of the variant
(rs6131) SELP with elevated glucose levels. It was also observed that SCA patients
under hydroxyurea treatment presented a reduction in monocyte count and LDH levels.
The third manuscript demonstrated that SCA individuals carriers of TTC haplotype in
the SELP gene presented lower levels of glucose than individuals with non-TTC
haplotypes. SAC individuals with the TTT haplotype presented reduced total cholesterol
and LDL-C levels when compared to those with non-TTT haplotype. Furthermore, it
was observed that SCA individuals carriers of βS CAR/BEN or CAR/CAR haplotypes
had high levels of total cholesterol.CONLUSIONS: Our results corroborated the
differences of the clinical and laboratory profiles between individuals with SCA and SC
hemoglobinopathy. Our study also confirmed that hydroxyurea treatment is associated
with improved inflammatory and hemolytic profiles; and that SCA individuals carriers
of the βs CAR/BEN or CAR/CAR haplotype may present a most severe clinical profile.
Furthermore, our data suggest that variants in the SELP and CD40L genes are
associated with clinical complications and laboratory markers related with vasoocclusion; and that haplotypes in the SELP gene may regulate classic biomarkers
involved in endothelial dysfunction in SCA patients.

MEMBROS DA BANCA:
Externa à Instituição - CARMEN SILVA BERTUZZO - UNICAMP
Interna - 796.762.515-34 - JULIANA PERRONE BEZERRA DE MENEZES FULLAM - UFBA
Externa à Instituição - MARIA DA CONCEICAO CHAGAS DE ALMEIDA - Fiocruz-Ba
Presidente - 183.851.845-20 - MARILDA DE SOUZA GONCALVES - UNICAMP
Externo ao Programa - 1221606 - VITOR ANTONIO FORTUNA