title: Reduced rate of sickle-related complications in Brazilian patients carrying HbF-promoting alleles at the BCL11A and HMIP-2 loci.
abstract: The presence of high levels of fetal haemoglobin (HbF) provides well-validated clinical benefits to patients with sickle cell anaemia (SCA). Nevertheless it has been difficult to show clear direct effects of the known genetic HbF modifiers, such as the enhancer polymorphisms for haematopoietic transcription factors BCL11A and MYB, on SCA severity. Investigating SCA patients from Brazil, with a high degree of European genetic admixture, we have detected strong effects of these variants on HbF levels. Critically, we have shown, for the first time, that the presence of such HbF-promoting variants leads to a reduced rate of SCA complications, especially stroke.
authors.affiliation: Haematology Centre, School of Medicine, University of Campinas- UNICAMP, Campinas, Brazil.
authors.forename: Flávia C
authors.initials: FC
authors.lastname: Leonardo
authors.affiliation: Haematology Centre, School of Medicine, University of Campinas- UNICAMP, Campinas, Brazil.
authors.forename: Ana F
authors.initials: AF
authors.lastname: Brugnerotto
authors.affiliation: Department of Genetics, Federal University of Pernambuco, Recife, Brazil.
authors.forename: Igor F
authors.initials: IF
authors.lastname: Domingos
authors.affiliation: Haematology Centre, School of Medicine, University of Campinas- UNICAMP, Campinas, Brazil.
authors.forename: Kleber Y
authors.initials: KY
authors.lastname: Fertrin
authors.affiliation: Haematology Centre, School of Medicine, University of Campinas- UNICAMP, Campinas, Brazil.
authors.forename: Dulcinéia M
authors.initials: DM
authors.lastname: de Albuquerque
authors.affiliation: Department of Genetics, Federal University of Pernambuco, Recife, Brazil.
authors.forename: Marcos A C
authors.initials: MA
authors.lastname: Bezerra
authors.affiliation: Haematology and Haemotherapy Foundation of Pernambuco (HEMOPE), Recife, Brazil.
authors.forename: Aderson S
authors.initials: AS
authors.lastname: Araújo
authors.affiliation: Haematology Centre, School of Medicine, University of Campinas- UNICAMP, Campinas, Brazil.
authors.forename: Sara T O
authors.initials: ST
authors.lastname: Saad
authors.affiliation: Haematology Centre, School of Medicine, University of Campinas- UNICAMP, Campinas, Brazil.
authors.forename: Fernando F
authors.initials: FF
authors.lastname: Costa
authors.affiliation: Department of Molecular Haematology, Division of Cancer Studies, King's College London Faculty of Life Sciences & Medicine, London, UK.
authors.forename: Stephan
authors.initials: S
authors.lastname: Menzel
authors.affiliation: Haematology Centre, School of Medicine, University of Campinas- UNICAMP, Campinas, Brazil.
authors.forename: Nicola
authors.initials: N
authors.lastname: Conran
authors.affiliation: Department of Molecular Haematology, Division of Cancer Studies, King's College London Faculty of Life Sciences & Medicine, London, UK.|Sickle Cell Branch, National Heart, Lung and Blood Institute, NIH, Bethesda, MD, USA.
authors.forename: Swee Lay
authors.initials: SL
authors.lastname: Thein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000755:Anemia, Sickle Cell / Q000150:complications*; D001938:Brazil; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D004742:Enhancer Elements, Genetic; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D016601:RNA-Binding Proteins / Q000235:genetics*; D012097:Repressor Proteins; D055815:Young Adult
chemical_list: C486563:BCL11A protein, human; D002352:Carrier Proteins; C498779:IGF2BP2 protein, human; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D005319:Fetal Hemoglobin
keywords: BCL11A; HMIP-2; HbF quantitative trait loci