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Pharmacogenomics. 2012 Oct;13(13):1487-500. doi: 10.2217/pgs.12.125.

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

Author information

1
Erasmus University Medical Center, Department of Cell Biology, Rotterdam, The Netherlands.

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 β-thalassemia 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 β-thalassemia major and intermedia patients and an independent cohort of β-thalassemia/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 β-thalassemia intermedia patients and is underrepresented in β-thalassemia/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.

PMID:
23057549
DOI:
10.2217/pgs.12.125
[Indexed for MEDLINE]

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