Repository logo
 
Publication

Genetic Modulators of Fetal Hemoglobin Expression and Ischemic Stroke Occurrence in African Descendant Children With Sickle Cell Anemia

2019-12Journal article Open access
Simple item page
dc.contributor.authorNicolau, M
dc.contributor.authorVargas, S
dc.contributor.authorSilva, M
dc.contributor.authorCoelho, A
dc.contributor.authorFerreira, E
dc.contributor.authorMendonça, J
dc.contributor.authorVieira, L
dc.contributor.authorKjöllerström, P
dc.contributor.authorMaia, R
dc.contributor.authorSilva, R
dc.contributor.authorDias, A
dc.contributor.authorFerreira, T
dc.contributor.authorMorais, A
dc.contributor.authorSoares, IM
dc.contributor.authorLavinha, J
dc.contributor.authorFaustino, P
dc.date.accessioned2020-05-15T13:57:27Z
dc.date.available2020-05-15T13:57:27Z
dc.date.issued2019-12
dc.description.abstractSickle cell anemia (SCA) is an autosomal recessive monogenic disease with significant clinical variability. Cerebrovascular disease, particularly ischemic stroke, is one of the most severe complications of SCA in children. This study aimed to investigate the influence of genetic variants on the levels of fetal hemoglobin (Hb F) and biochemical parameters related with chronic hemolysis, as well as on ischemic stroke risk, in ninety-one unrelated SCA patients, children of sub-Saharan progenitors. Our results show that a higher Hb F level has an inverse relationship with the occurrence of stroke, since the group of patients who suffered stroke presents a significantly lower mean Hb F level (5.34 ± 4.57% versus 9.36 ± 6.48%; p = 0.024). Furthermore, the co-inheritance of alpha-thalassemia improves the chronic hemolytic pattern, evidenced by a decreased reticulocyte count (8.61 ± 3.58% versus 12.85 ± 4.71%; p < 0.001). In addition, our findings have confirmed the importance of HBG2 and BCL11A loci in the regulation of Hb F expression in sub-Saharan African SCA patients, as rs7482144_A, rs11886868_C, and rs4671393_A alleles are significantly associated with a considerable increase in Hb F levels (p = 0.019, p = 0.026, and p = 0.028, respectively). Concerning KLF1, twelve different variants were identified, two of them novel. Seventy-three patients (80.2%) presented at least one variant in this gene. However, no correlation was observed between the presence of these variants and Hb F level, severity of hemolysis, or stroke occurrence, which is consistent with their in silico-predicted minor functional consequences. Thus, we conclude that the prevalence of functional KLF1 variants in a sub-Saharan African background does not seem to be relevant to SCA clinical modulation.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationAnn Hematol . 2019 Dec;98(12):2673-2681pt_PT
dc.identifier.doi10.1007/s00277-019-03783-ypt_PT
dc.identifier.urihttp://hdl.handle.net/10400.17/3442
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherSpringerpt_PT
dc.subjectAdolescentpt_PT
dc.subjectChildpt_PT
dc.subjectChild, Preschoolpt_PT
dc.subjectFemalept_PT
dc.subjectGenetic Locipt_PT
dc.subjectHumanspt_PT
dc.subjectMalept_PT
dc.subjectAfrican Continental Ancestry Grouppt_PT
dc.subjectAnemia, Sickle Cellpt_PT
dc.subjectBrain Ischemiapt_PT
dc.subjectFetal Hemoglobinpt_PT
dc.subjectGene Expression Regulationpt_PT
dc.subjectStrokept_PT
dc.subjectHDE PEDpt_PT
dc.subjectHDE NEU PEDpt_PT
dc.titleGenetic Modulators of Fetal Hemoglobin Expression and Ischemic Stroke Occurrence in African Descendant Children With Sickle Cell Anemiapt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage2681pt_PT
oaire.citation.issue12pt_PT
oaire.citation.startPage2673pt_PT
oaire.citation.titleAnnals of hematologypt_PT
oaire.citation.volume98pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Ann Hematol 2019_98_2673.pdf
Size:
406.98 KB
Format:
Adobe Portable Document Format
Download

Collections

PED - Artigos
NEU PED - Artigos