Repository logo
 
Publication

Biomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemia

2020-07Journal article Restricted access
Simple item page
dc.contributor.authorSilva, Marisa
dc.contributor.authorVargas, Sofia
dc.contributor.authorCoelho, Andreia
dc.contributor.authorFerreira, Emanuel
dc.contributor.authorMendonça, Joana
dc.contributor.authorVieira, Luís
dc.contributor.authorMaia, Raquel
dc.contributor.authorDias, Alexandra
dc.contributor.authorFerreira, Teresa
dc.contributor.authorMorais, Anabela
dc.contributor.authorMota Soares, Isabel
dc.contributor.authorLavinha, João
dc.contributor.authorSilva, Rita
dc.contributor.authorKjollerstrom, Paula
dc.contributor.authorFaustino, Paula
dc.date.accessioned2021-03-07T16:54:01Z
dc.date.available2021-03-07T16:54:01Z
dc.date.issued2020-07
dc.description.abstractWe investigated biomarkers and genetic modulators of the cerebral vasculopathy (CV) subphenotype in pediatric sickle cell anemia (SCA) patients of sub-Saharan African ancestry. We found that one VCAM1 promoter haplotype (haplotype 7) and VCAM1 single nucleotide variant rs1409419_T were associated with stroke events, stroke risk, as measured by time-averaged mean of maximum velocity in the middle cerebral artery, and with high serum levels of the hemolysis biomarker lactate dehydrogenase. Furthermore, VCAM-1 ligand coding gene ITGA4 variants rs113276800_A and rs3770138_T showed a positive association with stroke events. An additional positive relationship between a genetic variant and stroke risk was observed for ENPP1 rs1044498_A. Conversely, NOS3 variants were negatively associated with silent cerebral infarct events (VNTR 4b_allele and haplotype V) and CV globally (haplotype VII). The -alpha3.7kb–thal deletion did not show association with CV.However, it was associated with higher red blood cell and neutrophil counts, and lower mean corpuscular volume, mean corpuscular hemoglobin and red cell distribution width. Our results underline the importance of genetic modulators of the CV sub-phenotype and their potential as SCA therapeutic targets. We also propose that a biomarker panel comprising biochemical, hematological, imaging and genetic data would be instrumental for CV prediction, and prevention.pt_PT
dc.description.sponsorshipThis work was partially funded by Fundação para a Ciência e a Tecnologia (FCT) grant PIC/IC/83084/2007, ISAMB, and INSA project 2012DGH720. Additionally, it is a result of the GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), FCT.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBlood Cells Mol Dis. 2020 Jul;83:102436. doi: 10.1016/j.bcmd.2020.102436. Epub 2020 Apr 13.pt_PT
dc.identifier.doi10.1016/j.bcmd.2020.102436pt_PT
dc.identifier.issn1079-9796
dc.identifier.urihttp://hdl.handle.net/10400.18/7357
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevier/ Academic Presspt_PT
dc.relationDEVELOPMENT AND VALIDATION OF VASO-OCCLUSION EARLY PREDICTORS IN A MENDELIAN MODEL OF VASCULAR DISEASE
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/abs/pii/S1079979620300498?via%3Dihubpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectSickle Cell Anemiapt_PT
dc.subjectCerebral Vasculopathypt_PT
dc.subjectIschemi Strokept_PT
dc.subjectGenetic Modulatorspt_PT
dc.subjectBiomarkerspt_PT
dc.subjectDrepanocitosept_PT
dc.subjectDoenças Raraspt_PT
dc.subjectDoenças Genéticaspt_PT
dc.subjectGenética Humanapt_PT
dc.titleBiomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemiapt_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.startPage102436pt_PT
oaire.citation.titleBlood Cells, Molecules and Diseasespt_PT
oaire.citation.volume83pt_PT
oaire.fundingStream5646-ICCMS
person.familyNameDuarte Silva
person.familyNameFaustino
person.givenNameMarisa
person.givenNamePaula
person.identifier.ciencia-idF01A-353A-433E
person.identifier.orcid0000-0003-3575-1261
person.identifier.orcid0000-0002-6269-4867
person.identifier.ridM-3519-2014
person.identifier.scopus-author-id8158641100
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctAcesso de acordo com política editorial da revista.pt_PT
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication7496c9b7-1cbc-40ee-8ba7-eb29d0bb7430
relation.isAuthorOfPublication94303e78-8b7d-4e24-811d-3af3b1a4e330
relation.isAuthorOfPublication.latestForDiscovery7496c9b7-1cbc-40ee-8ba7-eb29d0bb7430
relation.isProjectOfPublication466fa8ec-15ed-4907-9ca9-5fc5c0916fc4
relation.isProjectOfPublication.latestForDiscovery466fa8ec-15ed-4907-9ca9-5fc5c0916fc4

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
Artigo SCA_vasculopatias Silva et al BCMD 2020.pdf
Size:
624.25 KB
Format:
Adobe Portable Document Format
Download

Collections

DGH - Artigos em revistas internacionais