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Whole transcriptome analysis of human erythropoietic cells during ontogenesis suggests a role of VEGFA gene as modulator of fetal hemoglobin and pharmacogenomic biomarker of treatment response to hydroxyurea in ß-type hemoglobinopathy patients.
Chondrou, Vasiliki; Kolovos, Petros; Sgourou, Argyro; Kourakli, Alexandra; Pavlidaki, Alexia; Kastrinou, Vlasia; John, Anne; Symeonidis, Argiris; Ali, Bassam R; Papachatzopoulou, Adamantia; Katsila, Theodora; Patrinos, George P.
Afiliación
  • Chondrou V; Department of Pharmacy, School of Health Sciences, University of Patras, University Campus, Rion, GR-265 04, Patras, Greece.
  • Kolovos P; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
  • Sgourou A; Hellenic Open University, Patras, Greece.
  • Kourakli A; Hematology Division, Department of Internal Medicine, Faculty of Medicine, University of Patras, Patras, Greece.
  • Pavlidaki A; Department of Pharmacy, School of Health Sciences, University of Patras, University Campus, Rion, GR-265 04, Patras, Greece.
  • Kastrinou V; Present address: Institut de Génétique et de Biologie Moléculaire et Cellulaire IGBMC/CNRS/INSERM/UDS, 67404 ILLKIRCH, BP 10142, CU de Strasbourg, France.
  • John A; Department of Pharmacy, School of Health Sciences, University of Patras, University Campus, Rion, GR-265 04, Patras, Greece.
  • Symeonidis A; Department of Pathology, College of Medicine & Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
  • Ali BR; Hematology Division, Department of Internal Medicine, Faculty of Medicine, University of Patras, Patras, Greece.
  • Papachatzopoulou A; Department of Pathology, College of Medicine & Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
  • Katsila T; Zayed Bin Sultan Center for Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
  • Patrinos GP; Laboratory of General Biology, Faculty of Medicine, University of Patras, Patras, Greece.
Hum Genomics ; 11(1): 24, 2017 10 23.
Article en En | MEDLINE | ID: mdl-29061162
BACKGROUND: Human erythropoiesis is characterized by distinct gene expression profiles at various developmental stages. Previous studies suggest that fetal-to-adult hemoglobin switch is regulated by a complex mechanism, in which many key players still remain unknown. Here, we report our findings from whole transcriptome analysis of erythroid cells, isolated from erythroid tissues at various developmental stages in an effort to identify distinct molecular signatures of each erythroid tissue. RESULTS: From our in-depth data analysis, pathway analysis, and text mining, we opted to focus on the VEGFA gene, given its gene expression characteristics. Selected VEGFA genomic variants, identified through linkage disequilibrium analysis, were explored further for their association with elevated fetal hemoglobin levels in ß-type hemoglobinopathy patients. Our downstream analysis of non-transfusion-dependent ß-thalassemia patients, ß-thalassemia major patients, compound heterozygous sickle cell disease/ß-thalassemia patients receiving hydroxyurea as fetal hemoglobin augmentation treatment, and non-thalassemic individuals indicated that VEGFA genomic variants were associated with disease severity in ß-thalassemia patients and hydroxyurea treatment efficacy in SCD/ß-thalassemia compound heterozygous patients. CONCLUSIONS: Our findings suggest that VEGFA may act as a modifier gene of human globin gene expression and, at the same time, serve as a genomic biomarker in ß-type hemoglobinopathy disease severity and hydroxyurea treatment efficacy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hemoglobina Fetal / Talasemia beta / Células Eritroides / Factor A de Crecimiento Endotelial Vascular / Hidroxiurea Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Hum Genomics Asunto de la revista: GENETICA Año: 2017 Tipo del documento: Article País de afiliación: Grecia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hemoglobina Fetal / Talasemia beta / Células Eritroides / Factor A de Crecimiento Endotelial Vascular / Hidroxiurea Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Hum Genomics Asunto de la revista: GENETICA Año: 2017 Tipo del documento: Article País de afiliación: Grecia Pais de publicación: Reino Unido