RRC ID 61255
Author Maroofi N, Azarkeivan A, Banihashemi S, Mohammadparast S, Aghajanirefah A, Banan M.
Title An enhancer haplotype may influence BCL11A expression levels and the response to hydroxyurea in β-thalassemia patients.
Journal Pharmacogenomics
Abstract AIM:To identify the BCL11A intron-2 enhancer linkage disequilibrium (LD) block, harboring two previously identified SNPs, associating with the hydroxyurea response in β-thalassemia patients and the functional significance of this region.
MATERIALS & METHODS:Several neighboring SNPs were genotyped in our cohort. The associating LD block was identified, and its function studied in K562 erythroid cells via CRISPR/Cas9 genome editing.
RESULTS:A haplotype harboring three tag SNPs correlated significantly with the HU-response and BCL11A transcript levels in the patients' reticulocytes. Two deletions encompassing this LD block significantly reduced BCL11A transcript levels in K562 cells.
CONCLUSION:Our data suggest an essential role for this LD block in BCL11A expression levels and the response to hydroxyurea in β-thalassemia patients.
Volume 18(10)
Pages 995-967
Published 2017-7-1
DOI 10.2217/pgs-2017-0019
PMID 28639471
MeSH Carrier Proteins / genetics* Cohort Studies Enhancer Elements, Genetic Gene Frequency Genotype HEK293 Cells Haplotypes Humans Hydroxyurea / administration & dosage Hydroxyurea / pharmacokinetics Hydroxyurea / therapeutic use* K562 Cells Linkage Disequilibrium Nuclear Proteins / genetics* Pharmacogenomic Variants* Polymorphism, Single Nucleotide* Repressor Proteins Reticulocytes / metabolism Transfection beta-Thalassemia / blood beta-Thalassemia / drug therapy* beta-Thalassemia / genetics
IF 2.339
Human and Animal Cells HUDEP-2(RCB4557)