Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.18/3873
Título: Hemorheological alterations in sickle cell anemia and their clinical consequences: the role of genetic modulators
Autor: Silva, Marisa
Vargas, Sofia
Coelho, Andreia
Dias, Alexandra
Ferreira, Teresa
Morais, Anabela
Maia, Raquel
Kjollerstrom, Paula
Lavinha, João
Faustino, Paula
Palavras-chave: Sickle Cell Disease
Genetic Modifiers
Doenças Genéticas
Data: Jun-2016
Editora: Instituto Nacional de Saúde Doutor Ricardo Jorge, IP
Resumo: Sickle cell anemia (SCA) is an autosomal recessive chronic hemolytic anemia, caused by homozygosity for the HBB:c.20A>T mutation. The disease presents with high clinical heterogeneity, stroke being the most devastating manifestation. This study aimed to identify genetic modulators of severe hemolysis and stroke risk in children with SCA, as well as understand their consequences at the hemorheological level. Sixty-six children with SCA were categorised according to their degree of cerebral vasculopathy (Stroke/Risk/Control). Relevant data were collected from patients’ medical records. Several polymorphic regions in genes related to vascular cell adhesion and tonus were characterized by molecular methodologies. Data analyses were performed using R software. Several in silico tools (e.g. TFBind, MatInspector) were applied to investigate the main variant consequences. Some genetic variants in vascular adhesion molecule-1 gene promoter and endothelial nitric oxide synthase gene were associated with higher levels of hemolysis and stroke events. They modify important transcription factor binding sites or disturb the corresponding protein structure/function. Our findings emphasize the relevance of the genetic variants in modulating the degree of hemolysis and development of cerebral vasculopathy due to their effect on gene expression, modification of protein biological activities related with erythrocyte/endothelial interactions and consequent hemorheological abnormalities in SCA.
Peer review: yes
URI: http://hdl.handle.net/10400.18/3873
Aparece nas colecções:DGH - Apresentações orais em encontros internacionais

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