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PLoS One. 2014 Mar 25;9(3):e92506. doi: 10.1371/journal.pone.0092506. eCollection 2014.

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

Author information

1
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.
2
Department of Microbiology, Parasitology and Haematology, Faculty of Medicine and Biomedical Sciences, University of Yaoundé 1, Yaoundé, Cameroon.
3
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.
4
Department of Public Health Sciences, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois, United States of America.
5
Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada.

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.

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.

PMID:
24667352
PMCID:
PMC3965431
DOI:
10.1371/journal.pone.0092506
[Indexed for MEDLINE]
Free PMC Article

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