Reference - Detail
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 |
Resource | |
Human and Animal Cells | HUDEP-2(RCB4557) |