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Genetic Modulators of Hemolytic Anemia in Angolan Children with Sickle Cell Anemia

2021-11Conference object Open access
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dc.contributor.authorGermano, Isabel
dc.contributor.authorSantos, Brígida
dc.contributor.authorDelgadinho, Mariana
dc.contributor.authorLopes, Pedro
dc.contributor.authorArez, Ana Paula
dc.contributor.authorBrito, Miguel
dc.contributor.authorFaustino, Paula
dc.date.accessioned2022-02-22T16:34:21Z
dc.date.available2022-02-22T16:34:21Z
dc.date.issued2021-11
dc.description.abstractSickle Cell Anemia (SCA) is a recessive genetic disease caused by the c.20A>T variant in HBB gene. It is characterised by sickled erythrocytes, chronic hemolytic anemia and vaso-occlusive events. However, these manifestations are heterogeneous due to environmental and genetic modifying factors. The aim of this study was to investigate genetic modifiers of hemolytic anemia in pediatric SCA patients living in Africa, where the disease is a severe public health problem. The study was conducted on 200 Angolan SCA 3-12 year-old children. Thirteen polymorphic regions in genes previously associated with vascular cell adhesion (VCAM1 and CD36), vascular tonus (NOS3) or erythrocyte hemoglobinisation (HBA), were genotyped using PCR, RFLP, Gap-PCR and Sanger sequencing. Hematological and biochemical phenotypes were obtained at steady state and clinical adverse events were collected from patients’ medical records. Results revealed a high level (67.5%) of α-thalassemia co-inheritance (del. 3.7kb in HBA), which improve patients’ health by delaying the onset of the disease, decreasing anemia and the number of blood transfusions. Two SNPs in CD36 (rs1984112 and rs1413661) showed impact on anemia severity. Particularly, genotypes containing the rs1413661_allele C revealed to be risk factors for severe anemia, as they were associated with lower hemoglobin levels, increased number of hospitalizations and transfusions. This is the first report associating this SNP with SCA pathology. Moreover, the rs1041163_allele C in VCAM1 was associated with lower LDH levels, inversely the rs2070744_allele C in NOS3 was associated with higher LDH levels and a higher number of hospitalizations, being a possible risk factor for increased hemolytic rate. This study contributed to the understanding of SCA complex pathophysiology. It confirmed the positive role of α-thal., both in SCA related anemia and in its clinical manifestations. In addition, it reinforced the importance of vascular cell adhesion in hemolytic anemia variability. In this context, we propose the SNP rs1413661 in CD36 as an important novel genetic modulator of SCA in Africa.pt_PT
dc.description.sponsorshipPartially funding by FCT/Aga Khan Dev. Network, #330842553pt_PT
dc.description.versionN/Apt_PT
dc.identifier.urihttp://hdl.handle.net/10400.18/7963
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.subjectSickle Cell Anemiapt_PT
dc.subjectDoenças Genéticaspt_PT
dc.subjectDrepanocitosept_PT
dc.subjectAngolapt_PT
dc.subjectModificadores Genéticospt_PT
dc.subjectAnemia Hemolíticapt_PT
dc.subjectAnemia das Células Falciformespt_PT
dc.titleGenetic Modulators of Hemolytic Anemia in Angolan Children with Sickle Cell Anemiapt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.citation.conferencePlace(online)pt_PT
oaire.citation.title25th Annual Meeting of the Portuguese Society of Human Genetics, 18-19 Novembro 2021pt_PT
person.familyNameFaustino
person.givenNamePaula
person.identifier.ciencia-idF01A-353A-433E
person.identifier.orcid0000-0002-6269-4867
person.identifier.ridM-3519-2014
person.identifier.scopus-author-id8158641100
rcaap.rightsopenAccesspt_PT
rcaap.typeconferenceObjectpt_PT
relation.isAuthorOfPublication94303e78-8b7d-4e24-811d-3af3b1a4e330
relation.isAuthorOfPublication.latestForDiscovery94303e78-8b7d-4e24-811d-3af3b1a4e330

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