期刊
PHARMACOGENOMICS
卷 13, 期 13, 页码 1487-1500出版社
FUTURE MEDICINE LTD
DOI: 10.2217/PGS.12.125
关键词
beta-thalassemia; hydroxyurea; KLF10; pharmacogenomics; sickle cell disease; transcription profiling
资金
- long-term EMBO fellowship [ALTF 71-2011]
- Research Promotion Foundation of Cyprus grant [RPF PiDeltaE046_02]
- Landsteiner Foundation for Blood Transfusion Research [1040]
- Netherlands Genomics Initiative
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 beta-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 beta-thalassemia major and intermedia patients and an independent cohort of beta-thalassemia/SCD compound heterozygous patients that do or do rot respond to HU treatment showed that the homozygous mutant state of a tagSNP in the KLF10 3'-UTR is not present in beta-thalassemia intermedia patients and is underrepresented in beta-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.
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