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Hemorheological alterations in sickle cell anemia and their clinical consequences – the role of genetic modulators

2016Journal article Restricted access
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dc.contributor.authorSilva, Marisa
dc.contributor.authorVargas, Sofia
dc.contributor.authorCoelho, Andreia
dc.contributor.authorDias, Alexandra
dc.contributor.authorFerreira, Teresa
dc.contributor.authorMorais, Anabela
dc.contributor.authorMaia, Raquel
dc.contributor.authorKjollerstrom, Paula
dc.contributor.authorLavinha, João
dc.contributor.authorFaustino, Paula
dc.date.accessioned2017-02-14T14:08:41Z
dc.date.available2017-02-14T14:08:41Z
dc.date.issued2016
dc.description.abstractSickle 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.pt_PT
dc.description.sponsorshipThis work was partially supported by FCT: grant PIC/IC/83084/2007.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationClin Hemorheol Microcirc. 2016;64(4):859-66. doi: 10.3233/CH-168048pt_PT
dc.identifier.doi10.3233/CH-168048pt_PT
dc.identifier.issn1386-0291
dc.identifier.urihttp://hdl.handle.net/10400.18/4163
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherIOS Presspt_PT
dc.relationDEVELOPMENT AND VALIDATION OF VASO-OCCLUSION EARLY PREDICTORS IN A MENDELIAN MODEL OF VASCULAR DISEASE
dc.relation.publisherversionhttp://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch168048pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectNOS3pt_PT
dc.subjectSickle Cell Diseasept_PT
dc.subjectVCAM-1pt_PT
dc.subjectGenetic Modulatorspt_PT
dc.subjectIn Silico Analysispt_PT
dc.subjectDoenças Genéticaspt_PT
dc.subjectDrepanocitosept_PT
dc.titleHemorheological alterations in sickle cell anemia and their clinical consequences – the role of genetic modulatorspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleDEVELOPMENT AND VALIDATION OF VASO-OCCLUSION EARLY PREDICTORS IN A MENDELIAN MODEL OF VASCULAR DISEASE
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5646-ICCMS/PIC%2FIC%2F83084%2F2007/PT
oaire.citation.endPage866pt_PT
oaire.citation.startPage859pt_PT
oaire.citation.titleClinical Hemorheology and Microcirculationpt_PT
oaire.citation.volume64(4)pt_PT
oaire.fundingStream5646-ICCMS
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication466fa8ec-15ed-4907-9ca9-5fc5c0916fc4
relation.isProjectOfPublication.latestForDiscovery466fa8ec-15ed-4907-9ca9-5fc5c0916fc4

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