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Genetic modifiers of HbF and response to hydroxyurea in sickle cell disease
Author(s) -
Green Nancy S.,
Barral Sandra
Publication year - 2011
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.22754
Subject(s) - fetal hemoglobin , medicine , disease , sickle cell anemia , phenotype , population , suppressor , locus (genetics) , transcription factor , gene , cell , genetics , immunology , bioinformatics , biology , fetus , pregnancy , environmental health
Fetal hemoglobin (HbF) levels are generally inversely proportional to severity of sickle cell disease (SCD) for given sickle phenotypes. Molecular regulation of HbF occurs through complex interactions cis and trans to the beta globin gene locus. Novel insights made through population‐based genetic epidemiologic studies of non‐anemic populations were replicated in SCD groups, despite large differences in HbF levels. Identification of the lymphoid transcription factor BCL11A as a key suppressor of HbF expression validates approaches using population genetics to study HbF expression. We review these methods and findings, and speculate on applying pharmaco‐genetics to optimize hydroxyurea therapy aimed at increasing HbF. Pediatr Blood Cancer 2011;56:177–181. © 2010 Wiley‐Liss, Inc.