論文 - 詳細
| RRC ID | 61255 |
|---|---|
| 著者 | Maroofi N, Azarkeivan A, Banihashemi S, Mohammadparast S, Aghajanirefah A, Banan M. |
| タイトル | An enhancer haplotype may influence BCL11A expression levels and the response to hydroxyurea in β-thalassemia patients. |
| ジャーナル | 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. |
| 巻・号 | 18(10) |
| ページ | 995-967 |
| 公開日 | 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 |
| リソース情報 | |
| ヒト・動物細胞 | HUDEP-2(RCB4557) |