title: Genetic modifiers of HbF and response to hydroxyurea in sickle cell disease.
abstract: 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.
authors.affiliation: Department of Pediatrics, Columbia University Medical Center, New York, New York 10032, USA. nsg11@columbia.edu
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Green
authors.forename: Sandra
authors.initials: S
authors.lastname: Barral
mesh_terms: D000755:Anemia, Sickle Cell / Q000188:drug therapy* / Q000235:genetics*; D000986:Antisickling Agents / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000235:genetics; D005319:Fetal Hemoglobin / Q000235:genetics*; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D009687:Nuclear Proteins / Q000235:genetics; D012097:Repressor Proteins
chemical_list: D000986:Antisickling Agents; C486563:BCL11A protein, human; D002352:Carrier Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D005319:Fetal Hemoglobin; D006918:Hydroxyurea