title: The role of BCL11A and HMIP-2 polymorphisms on endogenous and hydroxyurea induced levels of fetal hemoglobin in sickle cell anemia patients from southern Brazil.
abstract: High levels of fetal hemoglobin (HbF) reduce sickle cell anemia (SCA) morbidity and mortality. HbF levels vary considerably and there is a strong genetic component that influences HbF production. Genetic polymorphisms at three quantitative trait loci (QTL): Xmn1-HBG2, HMIP-2 and BCL11A, have been shown to influence HbF levels and disease severity in SCA. Hydroxyurea (HU) is a drug that increases HbF. We investigated the influence of single nucleotide polymorphisms (SNPs) at the Xmn1-HBG2 (rs7482144); BCL11A (rs1427407, rs4671393 and rs11886868); and HMIP-2 (rs9399137 and rs9402686) loci on baseline and HU-induced HbF levels in 111 HbSS patients. We found that both BCL11A and HMIP-2 were associated with increased endogenous levels of HbF. Interestingly, we also found that BCL11A was associated with higher induction of HbF with HU. This effect was independent of the effect of BCL11A on baseline HbF levels. Additional studies will be needed to validate these findings and explain the ample inter-individual variations in HbF levels at baseline and HU-induced in patients with SCA.
authors.affiliation: Medical Sciences, Universidade Federal do Rio Grande do Sul (UFGRS); Hematology and Bone Marrow Transplantation Service of the Hospital de Clínicas de Porto Alegre (HCPA). Electronic address: drjrf@terra.com.br.
authors.forename: João Ricardo
authors.initials: JR
authors.lastname: Friedrisch
authors.affiliation: Texas Children's Hematology Center, Baylor College of Medicine, Department of Pediatrics, Houston, TX, USA. Electronic address: vsheehan@bcm.edu.
authors.forename: Vivien
authors.initials: V
authors.lastname: Sheehan
authors.affiliation: Texas Children's Hematology Center, Baylor College of Medicine, Department of Pediatrics, Houston, TX, USA. Electronic address: jmflanag@txch.edu.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Flanagan
authors.affiliation: Texas Children's Hematology Center, Baylor College of Medicine, Department of Pediatrics, Houston, TX, USA. Electronic address: alessandro.baldan@bcm.edu.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Baldan
authors.affiliation: Texas Children's Hematology Center, Baylor College of Medicine, Department of Pediatrics, Houston, TX, USA. Electronic address: carly.summarell@bcm.edu.
authors.forename: Carly C Ginter
authors.initials: CC
authors.lastname: Summarell
authors.affiliation: Hematology and Bone Marrow Transplantation Service of the Hospital de Clínicas de Porto Alegre (HCPA). Electronic address: cbittar@hcpa.edu.br.
authors.forename: Christina Matzembacher
authors.initials: CM
authors.lastname: Bittar
authors.affiliation: Universidade de Santa Cruz do Sul (UNISC), Santa Cruz do Sul, RS, Brazil. Electronic address: brunokf@gmail.com.
authors.forename: Bruno Kras
authors.initials: BK
authors.lastname: Friedrisch
authors.affiliation: Hematology and Bone Marrow Transplantation Service of the Hospital de Clínicas de Porto Alegre (HCPA). Electronic address: ianaewilke@bol.com.br.
authors.forename: Ianaê Indiara
authors.initials: II
authors.lastname: Wilke
authors.affiliation: Hematology and Bone Marrow Transplantation Service of the Hospital de Clínicas de Porto Alegre (HCPA). Electronic address: camilablosribeiro@gmail.com.
authors.forename: Camila Blos
authors.initials: CB
authors.lastname: Ribeiro
authors.affiliation: Hematology and Bone Marrow Transplantation Service of the Hospital de Clínicas de Porto Alegre (HCPA). Electronic address: ldaudt@hcpa.edu.br.
authors.forename: Liane Esteves
authors.initials: LE
authors.lastname: Daudt
authors.affiliation: Hematology and Bone Marrow Transplantation Service of the Hospital de Clínicas de Porto Alegre (HCPA); Medical Sciences, UFGRS, Santa Cruz do Sul, RS, Brazil. Electronic address: lsilla@hcpa.edu.br.
authors.forename: Lucia Mariano
authors.initials: LM
authors.lastname: da Rocha Silla
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000235:genetics; D001938:Brazil; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis* / Q000187:drug effects; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics*; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D012097:Repressor Proteins; D055815:Young Adult
chemical_list: C486563:BCL11A protein, human; D002352:Carrier Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D005319:Fetal Hemoglobin; D008666:Metalloendopeptidases; C068038:mitochondrial intermediate peptidase; D006918:Hydroxyurea
keywords: BCL11A; HMIP-2; Sickle cell anemia; Single nucleotide polymorphism