title: BCL11A enhancer haplotypes and fetal hemoglobin in sickle cell anemia.
abstract: BACKGROUND
  Fetal hemoglobin (HbF) levels in sickle cell anemia patients vary. We genotyped polymorphisms in the erythroid-specific enhancer of BCL11A to see if they might account for the very high HbF associated with the Arab-Indian (AI) haplotype and Benin haplotype of sickle cell anemia.
  
  
  RESULTS
  Six BCL112A enhancer SNPs and their haplotypes were studied in Saudi Arabs from the Eastern Province and Indian patients with AI haplotype (HbF ~20%), African Americans (HbF ~7%), and Saudi Arabs from the Southwestern Province (HbF ~12%). Four SNPs (rs1427407, rs6706648, rs6738440, and rs7606173) and their haplotypes were consistently associated with HbF levels. The distributions of haplotypes differ in the 3 cohorts but not their genetic effects: the haplotype TCAG was associated with the lowest HbF level and the haplotype GTAC was associated with the highest HbF level and differences in HbF levels between carriers of these haplotypes in all cohorts were approximately 6%.
  
  
  CONCLUSIONS
  Common HbF BCL11A enhancer haplotypes in patients with African origin and AI sickle cell anemia have similar effects on HbF but they do not explain their differences in HbF.
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States. Electronic address: sebas@bu.edu.
authors.forename: P
authors.initials: P
authors.lastname: Sebastiani
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA, United States.
authors.forename: J J
authors.initials: JJ
authors.lastname: Farrell
authors.affiliation: Sickle Cell Disease Research Center and Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: A
authors.initials: A
authors.lastname: Alsultan
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States.
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA, United States.
authors.forename: H L
authors.initials: HL
authors.lastname: Edward
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States.
authors.forename: H
authors.initials: H
authors.lastname: Shappell
authors.affiliation: College of Public Health and Human Sciences, Oregon State University, Corvallis, OR, United States.
authors.forename: H
authors.initials: H
authors.lastname: Bae
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States.
authors.forename: J N
authors.initials: JN
authors.lastname: Milton
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA, United States.
authors.forename: C T
authors.initials: CT
authors.lastname: Baldwin
authors.affiliation: Department of Internal Medicine, College of Medicine, University of Dammam, Dammam, Saudi Arabia.
authors.forename: A M
authors.initials: AM
authors.lastname: Al-Rubaish
authors.affiliation: Department of Pediatrics, Maternity & Child Hospital, Dammam, Saudi Arabia.
authors.forename: Z
authors.initials: Z
authors.lastname: Naserullah
authors.affiliation: Department of Internal Medicine, College of Medicine, University of Dammam, Dammam, Saudi Arabia.
authors.forename: F
authors.initials: F
authors.lastname: Al-Muhanna
authors.affiliation: Department of Hematology, King Fahd Hospital, Hafof, Al-Ahsa, Saudi Arabia.
authors.forename: A
authors.initials: A
authors.lastname: Alsuliman
authors.affiliation: Deptartment of Biochemistry, Pt. J.N.M. Medical College, Raipur, Chattisgarh, India.
authors.forename: P K
authors.initials: PK
authors.lastname: Patra
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA, United States.
authors.forename: L A
authors.initials: LA
authors.lastname: Farrer
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA, United States.
authors.forename: D
authors.initials: D
authors.lastname: Ngo
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA, United States.
authors.forename: V
authors.initials: V
authors.lastname: Vathipadiekal
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA, United States.
authors.forename: D H K
authors.initials: DH
authors.lastname: Chui
authors.affiliation: Prince Mohammed Center for Research & Consultation Studies, University of Dammam, Dammam, Saudi Arabia.
authors.forename: A K
authors.initials: AK
authors.lastname: Al-Ali
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA, United States.
authors.forename: M H
authors.initials: MH
authors.lastname: Steinberg
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics; D000755:Anemia, Sickle Cell / Q000235:genetics*; D018912:Arabs / Q000235:genetics; D044466:Asian People / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins; D055815:Young Adult
chemical_list: C486563:BCL11A protein, human; D002352:Carrier Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D005319:Fetal Hemoglobin
keywords: Genetic association; Haplotype analysis; Hemoglobin; Sickle cell disease