Association of variants at BCL11A and HBS1L-MYB with hemoglobin F and hospitalization rates among sickle cell patients in Cameroon

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dc.contributor.authorWonkam, Ambroiseen_ZA
dc.contributor.authorBitoungui, Valentina J Ngoen_ZA
dc.contributor.authorVorster, Anna Aen_ZA
dc.contributor.authorRamesar, Rajen_ZA
dc.contributor.authorCooper, Richard Sen_ZA
dc.contributor.authorTayo, Bamideleen_ZA
dc.contributor.authorLettre, Guillaumeen_ZA
dc.contributor.authorNgogang, Jeanneen_ZA
dc.date.accessioned2015-11-23T12:32:58Z
dc.date.available2015-11-23T12:32:58Z
dc.date.issued2014en_ZA
dc.description.abstractBACKGROUND: 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. Methods and FINDINGS: 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.en_ZA
dc.identifier.apacitationWonkam, A., Bitoungui, V. J. N., Vorster, A. A., Ramesar, R., Cooper, R. S., Tayo, B., ... Ngogang, J. (2014). Association of variants at BCL11A and HBS1L-MYB with hemoglobin F and hospitalization rates among sickle cell patients in Cameroon. <i>PLoS One</i>, http://hdl.handle.net/11427/15316en_ZA
dc.identifier.chicagocitationWonkam, Ambroise, Valentina J Ngo Bitoungui, Anna A Vorster, Raj Ramesar, Richard S Cooper, Bamidele Tayo, Guillaume Lettre, and Jeanne Ngogang "Association of variants at BCL11A and HBS1L-MYB with hemoglobin F and hospitalization rates among sickle cell patients in Cameroon." <i>PLoS One</i> (2014) http://hdl.handle.net/11427/15316en_ZA
dc.identifier.citationWonkam, A., Ngo Bitoungui, V. J., Vorster, A. A., Ramesar, R., Cooper, R. S., Tayo, B., ... & Ngogang, J. (2014). Association of variants at BCL11A and HBS1L-MYB with hemoglobin F and hospitalization rates among sickle cell patients in Cameroon. PloS one, 9(3), e92506. doi:10.1371/journal.pone.0092506en_ZA
dc.identifier.ris TY - Journal Article AU - Wonkam, Ambroise AU - Bitoungui, Valentina J Ngo AU - Vorster, Anna A AU - Ramesar, Raj AU - Cooper, Richard S AU - Tayo, Bamidele AU - Lettre, Guillaume AU - Ngogang, Jeanne AB - 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. Methods and FINDINGS: 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. DA - 2014 DB - OpenUCT DO - 10.1371/journal.pone.0092506 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - Association of variants at BCL11A and HBS1L-MYB with hemoglobin F and hospitalization rates among sickle cell patients in Cameroon TI - Association of variants at BCL11A and HBS1L-MYB with hemoglobin F and hospitalization rates among sickle cell patients in Cameroon UR - http://hdl.handle.net/11427/15316 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15316
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0092506
dc.identifier.vancouvercitationWonkam A, Bitoungui VJN, Vorster AA, Ramesar R, Cooper RS, Tayo B, et al. Association of variants at BCL11A and HBS1L-MYB with hemoglobin F and hospitalization rates among sickle cell patients in Cameroon. PLoS One. 2014; http://hdl.handle.net/11427/15316.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Human Geneticsen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2014 Wonkam et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherGenetic locien_ZA
dc.subject.otherHaplotypesen_ZA
dc.subject.otherCameroonen_ZA
dc.subject.otherHuman geneticsen_ZA
dc.subject.otherAfrican Americansen_ZA
dc.subject.otherHemoglobinen_ZA
dc.subject.otherHigh performance liquid chromatographyen_ZA
dc.subject.otherAfricaen_ZA
dc.titleAssociation of variants at BCL11A and HBS1L-MYB with hemoglobin F and hospitalization rates among sickle cell patients in Cameroonen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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