Biomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemia
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.17/3539 |
Resumo: | We 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. |
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Biomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemiaAdolescentAfrica South of the SaharaAnemia, Sickle CellCase-Control StudiesChildChild, PreschoolFemaleGenetic MarkersGenetic Predisposition to DiseaseHaplotypesHumansMalePhosphoric Diester HydrolasesPolymorphism, Single NucleotidePyrophosphatasesStrokeVascular Cell Adhesion Molecule-1HDE HEM PEDHDE NEU PEDWe 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.ElsevierRepositório do Centro Hospitalar Universitário de Lisboa Central, EPESilva, MVargas, SCoelho, AFerreira, EMendonça, JVieira, LMaia, RDias, AFerreira, TMorais, ASoares, IMLavinha, JSilva, RKjöllerström, PFaustino, P2021-01-22T15:00:00Z20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.17/3539engBlood Cells Mol Dis . 2020 Jul;83:10243610.1016/j.bcmd.2020.102436info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-03-10T09:43:29Zoai:repositorio.chlc.min-saude.pt:10400.17/3539Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:20:50.954455Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Biomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemia |
title |
Biomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemia |
spellingShingle |
Biomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemia Silva, M Adolescent Africa South of the Sahara Anemia, Sickle Cell Case-Control Studies Child Child, Preschool Female Genetic Markers Genetic Predisposition to Disease Haplotypes Humans Male Phosphoric Diester Hydrolases Polymorphism, Single Nucleotide Pyrophosphatases Stroke Vascular Cell Adhesion Molecule-1 HDE HEM PED HDE NEU PED |
title_short |
Biomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemia |
title_full |
Biomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemia |
title_fullStr |
Biomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemia |
title_full_unstemmed |
Biomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemia |
title_sort |
Biomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemia |
author |
Silva, M |
author_facet |
Silva, M Vargas, S Coelho, A Ferreira, E Mendonça, J Vieira, L Maia, R Dias, A Ferreira, T Morais, A Soares, IM Lavinha, J Silva, R Kjöllerström, P Faustino, P |
author_role |
author |
author2 |
Vargas, S Coelho, A Ferreira, E Mendonça, J Vieira, L Maia, R Dias, A Ferreira, T Morais, A Soares, IM Lavinha, J Silva, R Kjöllerström, P Faustino, P |
author2_role |
author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório do Centro Hospitalar Universitário de Lisboa Central, EPE |
dc.contributor.author.fl_str_mv |
Silva, M Vargas, S Coelho, A Ferreira, E Mendonça, J Vieira, L Maia, R Dias, A Ferreira, T Morais, A Soares, IM Lavinha, J Silva, R Kjöllerström, P Faustino, P |
dc.subject.por.fl_str_mv |
Adolescent Africa South of the Sahara Anemia, Sickle Cell Case-Control Studies Child Child, Preschool Female Genetic Markers Genetic Predisposition to Disease Haplotypes Humans Male Phosphoric Diester Hydrolases Polymorphism, Single Nucleotide Pyrophosphatases Stroke Vascular Cell Adhesion Molecule-1 HDE HEM PED HDE NEU PED |
topic |
Adolescent Africa South of the Sahara Anemia, Sickle Cell Case-Control Studies Child Child, Preschool Female Genetic Markers Genetic Predisposition to Disease Haplotypes Humans Male Phosphoric Diester Hydrolases Polymorphism, Single Nucleotide Pyrophosphatases Stroke Vascular Cell Adhesion Molecule-1 HDE HEM PED HDE NEU PED |
description |
We 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. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020 2020-01-01T00:00:00Z 2021-01-22T15:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.17/3539 |
url |
http://hdl.handle.net/10400.17/3539 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Blood Cells Mol Dis . 2020 Jul;83:102436 10.1016/j.bcmd.2020.102436 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799131304778792960 |