Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.18/4163
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: NOS3
Sickle Cell Disease
Genetic Modulators
In Silico Analysis
Doenças Genéticas
Data: 2016
Editora: IOS Press
Citação: Clin Hemorheol Microcirc. 2016;64(4):859-66. doi: 10.3233/CH-168048
Resumo: Sickle cell anemia (SCA) is an autosomal recessive disease caused by the HBB:c.20A>T mutation that leads to hemoglobin S synthesis. The disease presents with high clinical heterogeneity characterized by chronic hemolysis, recurrent episodes of vaso-oclusion and infection. This work aimed to characterize by in silico studies some genetic modulators of severe hemolysis and stroke risk in children with SCA, and understand their consequences at the hemorheological level. Association studies were performed between hemolysis biomarkers as well as the degree of cerebral vasculopathy and the inheritance of several polymorphic regions in genes related with vascular cell adhesion and vascular tonus in pediatric SCA patients. In silico tools (e.g. MatInspector) were applied to investigate the main variant consequences. Variants in vascular adhesionmolecule-1 (VCAM1) gene promoter and endothelial nitric oxide synthase (NOS3) gene were significantly associated with higher degree of hemolysis and stroke events. They potentially modify transcription factor binding sites (e.g. VCAM1 rs1409419 T allele may lead to an EVI1 gain) or disturb the corresponding protein structure/function. Our findings emphasize the relevance of genetic variation inmodulating the disease severity due to their effect on gene expression or modification of protein biological activities related with sickled erythrocyte/endothelial interactions and consequent hemorheological abnormalities.
Peer review: yes
URI: http://hdl.handle.net/10400.18/4163
DOI: 10.3233/CH-168048
ISSN: 1386-0291
Versão do Editor: http://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch168048
Aparece nas colecções:DGH - Artigos em revistas internacionais

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