title: Association of variants at BCL11A and HBS1L-MYB with hemoglobin F and hospitalization rates among sickle cell patients in Cameroon.
abstract: BACKGROUND
  Genetic variation at loci influencing adult levels of HbF have been shown to modify the clinical course of sickle cell disease (SCD). Data on this important aspect of SCD have not yet been reported from West Africa. We investigated the relationship between HbF levels and the relevant genetic loci in 610 patients with SCD (98% HbSS homozygotes) from Cameroon, and compared the results to a well-characterized African-American cohort.
  
  
  RESULTS
  Socio-demographic and clinical features were collected and medical records reviewed. Only patients >5 years old, who had not received a blood transfusion or treatment with hydroxyurea were included. Hemoglobin electrophoresis and a full blood count were conducted upon arrival at the hospital. RFLP-PCR was used to describe the HBB gene haplotypes. SNaPshot PCR, Capillary electrophoresis and cycle sequencing were used for the genotyping of 10 selected SNPs. Genetic analysis was performed with PLINK software and statistical models in the statistical package R. Allele frequencies of relevant variants at BCL11A were similar to those detected in African Americans; although the relationships with Hb F were significant (p <.001), they explained substantially less of the variance in HbF than was observed among African Americans (∼ 2% vs 10%). SNPs in HBS1L-MYB region (HMIP) likewise had a significant impact on HbF, however, we did not find an association between HbF and the variations in HBB cluster and OR51B5/6 locus on chromosome 11p, due in part to the virtual absence of the Senegal and Indian Arab haplotypes. We also found evidence that selected SNPs in HBS1L-MYB region (HMIP) and BCL11A affect both other hematological indices and rates of hospitalization.
  
  
  CONCLUSIONS
  This study has confirmed the associations of SNPs in BCL11A and HBS1L-MYB and fetal haemoglobin in Cameroonian SCA patients; hematological indices and hospitalization rates were also associated with specific allelic variants.
authors.affiliation: Division of Human Genetics, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, Republic of South Africa.
authors.forename: Ambroise
authors.initials: A
authors.lastname: Wonkam
authors.affiliation: Department of Microbiology, Parasitology and Haematology, Faculty of Medicine and Biomedical Sciences, University of Yaoundé 1, Yaoundé, Cameroon.
authors.forename: Valentina J
authors.initials: VJ
authors.lastname: Ngo Bitoungui
authors.affiliation: Division of Human Genetics, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, Republic of South Africa.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Vorster
authors.affiliation: Division of Human Genetics, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, Republic of South Africa; UCT/MRC Human Genetics Research Unit, Division of Human Genetics, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, Republic of South Africa.
authors.forename: Raj
authors.initials: R
authors.lastname: Ramesar
authors.affiliation: Department of Public Health Sciences, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois, United States of America.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Cooper
authors.affiliation: Department of Public Health Sciences, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois, United States of America.
authors.forename: Bamidele
authors.initials: B
authors.lastname: Tayo
authors.affiliation: Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lettre
authors.affiliation: Department of Microbiology, Parasitology and Haematology, Faculty of Medicine and Biomedical Sciences, University of Yaoundé 1, Yaoundé, Cameroon.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Ngogang
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000235:genetics; D000755:Anemia, Sickle Cell / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D002163:Cameroon / Q000453:epidemiology; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004913:Erythrocytes, Abnormal / Q000378:metabolism / Q000473:pathology; D005260:Female; D005319:Fetal Hemoglobin / Q000378:metabolism*; D005500:Follow-Up Studies; D019204:GTP-Binding Proteins / Q000235:genetics*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D010445:Peptide Elongation Factors / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics*; D012097:Repressor Proteins; D055815:Young Adult
chemical_list: C486563:BCL11A protein, human; D002352:Carrier Proteins; D018840:HSP70 Heat-Shock Proteins; D009687:Nuclear Proteins; D010445:Peptide Elongation Factors; D020598:Proto-Oncogene Proteins c-myb; D012097:Repressor Proteins; D005319:Fetal Hemoglobin; D019204:GTP-Binding Proteins; C000628258:HBS1L protein, human