title: BCL11A is a major HbF quantitative trait locus in three different populations with beta-hemoglobinopathies.
abstract: Increased HbF levels or F-cell (HbF containing erythrocyte) numbers can ameliorate the disease severity of beta-thalassemia major and sickle cell anemia. Recent genome-wide association studies reported that single nucleotide polymorphisms (SNPs) in BCL11A gene on chromosome 2p16.1 were correlated with F-cells among healthy northern Europeans, and HbF among Sardinians with beta-thalassemias. In this study, we showed that SNPs in BCL11A were associated with F-cell numbers in Chinese with beta-thalassemia trait, and with HbF levels in Thais with either beta-thalassemia or HbE trait and in African Americans with sickle cell anemia. Taken together, the data suggest that the functional motifs responsible for modulating F-cells and HbF levels reside within a 3 kb region in the second intron of BCL11A.
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Sedgewick
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
authors.forename: Nadia
authors.initials: N
authors.lastname: Timofeev
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
authors.forename: Paola
authors.initials: P
authors.lastname: Sebastiani
authors.affiliation: Department of Pathology, the University of Hong Kong Faculty of Medicine, and Queen Mary Hospital, Hong Kong, China.
authors.forename: Jason C C
authors.initials: JCC
authors.lastname: So
authors.affiliation: Department of Pathology, the University of Hong Kong Faculty of Medicine, and Queen Mary Hospital, Hong Kong, China.
authors.forename: Edmond S K
authors.initials: ESK
authors.lastname: Ma
authors.affiliation: Department of Pathology, the University of Hong Kong Faculty of Medicine, and Queen Mary Hospital, Hong Kong, China.
authors.forename: Li Chong
authors.initials: LC
authors.lastname: Chan
authors.affiliation: Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Goonnapa
authors.initials: G
authors.lastname: Fucharoen
authors.affiliation: Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Supan
authors.initials: S
authors.lastname: Fucharoen
authors.affiliation: Division of Hematology/Oncology, Center of Excellence in Sickle Cell Disease, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Cynara G
authors.initials: CG
authors.lastname: Barbosa
authors.affiliation: Genetics Program, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Badri N
authors.initials: BN
authors.lastname: Vardarajan
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.|Genetics Program, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.|Departments of Neurology, Genetics & Genomics, and Epidemiology, Boston University Schools of Medicine and Public Health, Boston, Massachusetts, USA.
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Farrer
authors.affiliation: Genetics Program, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.|Center for Human Genetics, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Clinton T
authors.initials: CT
authors.lastname: Baldwin
authors.affiliation: Division of Hematology/Oncology, Center of Excellence in Sickle Cell Disease, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Steinberg
authors.affiliation: Division of Hematology/Oncology, Center of Excellence in Sickle Cell Disease, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
authors.forename: David H K
authors.initials: DHK
authors.lastname: Chui
mesh_terms: D001741:Black or African American / Q000235:genetics; D000755:Anemia, Sickle Cell / Q000235:genetics / Q000378:metabolism; D044466:Asian People / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D005319:Fetal Hemoglobin / Q000235:genetics* / Q000378:metabolism; D006453:Hemoglobinopathies / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007438:Introns; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012097:Repressor Proteins; D013785:Thailand; D017086:beta-Thalassemia / Q000235:genetics / Q000378:metabolism
chemical_list: C486563:BCL11A protein, human; D002352:Carrier Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D005319:Fetal Hemoglobin