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Biomarkers and Genetic Modulators of Cerebral Vasculopathy in Sub-Saharan Ancestry Children With Sickle Cell Anemia

2020Journal article Open access
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dc.contributor.authorSilva, M
dc.contributor.authorVargas, S
dc.contributor.authorCoelho, A
dc.contributor.authorFerreira, E
dc.contributor.authorMendonça, J
dc.contributor.authorVieira, L
dc.contributor.authorMaia, R
dc.contributor.authorDias, A
dc.contributor.authorFerreira, T
dc.contributor.authorMorais, A
dc.contributor.authorSoares, IM
dc.contributor.authorLavinha, J
dc.contributor.authorSilva, R
dc.contributor.authorKjöllerström, P
dc.contributor.authorFaustino, P
dc.date.accessioned2021-01-22T15:00:00Z
dc.date.available2021-01-22T15:00:00Z
dc.date.issued2020
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.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBlood Cells Mol Dis . 2020 Jul;83:102436pt_PT
dc.identifier.doi10.1016/j.bcmd.2020.102436pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.17/3539
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.subjectAdolescentpt_PT
dc.subjectAfrica South of the Saharapt_PT
dc.subjectAnemia, Sickle Cellpt_PT
dc.subjectCase-Control Studiespt_PT
dc.subjectChildpt_PT
dc.subjectChild, Preschoolpt_PT
dc.subjectFemalept_PT
dc.subjectGenetic Markerspt_PT
dc.subjectGenetic Predisposition to Diseasept_PT
dc.subjectHaplotypespt_PT
dc.subjectHumanspt_PT
dc.subjectMalept_PT
dc.subjectPhosphoric Diester Hydrolasespt_PT
dc.subjectPolymorphism, Single Nucleotidept_PT
dc.subjectPyrophosphatasespt_PT
dc.subjectStrokept_PT
dc.subjectVascular Cell Adhesion Molecule-1pt_PT
dc.subjectHDE HEM PEDpt_PT
dc.subjectHDE NEU PEDpt_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.citation.startPage102436pt_PT
oaire.citation.titleBlood cells, molecules & diseasespt_PT
oaire.citation.volume83pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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