KLF10 gene expression is associated with high fetal hemoglobin levels and with response to hydroxyurea treatment in β-hemoglobinopathy patients-Reference-Cited by-同舟云学术

KLF10 gene expression is associated with high fetal hemoglobin levels and with response to hydroxyurea treatment in β-hemoglobinopathy patients

Published:2012-10 Issue:13 Volume:13 Page:1487-1500
ISSN:1462-2416
Container-title:Pharmacogenomics
language:en
Short-container-title:Pharmacogenomics

Author:

Borg Joseph¹,Phylactides Marios²,Bartsakoulia Marina³,Tafrali Christina³,Lederer Carsten²,Felice Alexander E⁴,Papachatzopoulou Adamantia⁵,Kourakli Alexandra⁶,Stavrou Eleana F⁵,Christou Soteroula⁷,Hou Jun⁸,Karkabouna Sophia⁹,Lappa-Manakou Christina⁹,Özgur Zeliha¹⁰,van IJcken Wilfred¹⁰,von Lindern Marieke¹¹,Grosveld Frank G¹²,Georgitsi Marianthi³,Kleanthous Marina²,Philipsen Sjaak⁸,Patrinos George P¹³

Affiliation:

1. Erasmus University Medical Center, Department of Cell Biology, Rotterdam, The Netherlands and Department of Applied Biomedical Science, Faculty of Health Sciences, University of Malta, Malta

2. Molecular Genetics Thalassemia Department, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus

3. University of Patras, School of Health Sciences, Department of Pharmacy, University Campus, Rion, GR-26504, Patras, Greece

4. Laboratory of Molecular Genetics, Department of Physiology & Biochemistry, University of Malta, Msida, Malta

5. University of Patras, School of Medicine, University Campus, Rion, GR-26504, Patras, Greece

6. Department of Internal Medicine, Hematology Unit, University of Patras Hospital, Patras, Greece

7. Thalassemia Centre, Archbishop Makarios III Hospital, Nicosia, Cyprus

8. Erasmus University Medical Center, Department of Cell Biology, Rotterdam, The Netherlands and Erasmus University Medical Center, Netherlands Consortium for Systems Biology, Rotterdam, The Netherlands

9. Erasmus University Medical Center, Department of Cell Biology, Rotterdam, The Netherlands

10. Erasmus University Medical Center, Department of Biomics, Rotterdam, The Netherlands

11. Erasmus University Medical Center, Department of Hematology, Rotterdam, The Netherlands

12. Erasmus University Medical Center, Department of Cell Biology, Rotterdam, The Netherlands and Erasmus University Medical Center, Netherlands Consortium for Systems Biology, Rotterdam, The Netherlands and Erasmus University Medical Center, Center for Biomedical Genetics, Rotterdam, The Netherlands

13. University of Patras, School of Health Sciences, Department of Pharmacy, University Campus, Rion, GR-26504, Patras, Greece.

Abstract

Aim: In humans, fetal hemoglobin (HbF) production is controlled by many intricate mechanisms that, to date, remain only partly understood. Patients & methods: Pharmacogenomic analysis of the effects of hydroxyurea (HU) on HbF production was undertaken in a collection of Hellenic βthalassemia and sickle cell disease (SCD) compound heterozygotes and a collection of healthy and KLF1-haploinsufficient Maltese adults, to identify genomic signatures that follow high HbF patterns. Results: KLF10 emerged as a top candidate. Moreover, genotype analysis of βthalassemia major and intermedia patients and an independent cohort of βthalassemia/SCD compound heterozygous patients that do or do not respond to HU treatment showed that the homozygous mutant state of a tagSNP in the KLF10 3’UTR is not present in βthalassemia intermedia patients and is underrepresented in βthalassemia/SCD compound heterozygous patients that respond well to HU treatment. Conclusion: These data suggest that KLF10 may constitute a pharmacogenomic marker to discriminate between response and nonresponse to HU treatment. Original submitted: 2 May 2012; Revision submitted: 17 July 2012

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

Link

https://www.futuremedicine.com/doi/pdf/10.2217/pgs.12.125

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