Browsing by Author "Vorster, Anna A"

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    Association of variants at BCL11A and HBS1L-MYB with hemoglobin F and hospitalization rates among sickle cell patients in Cameroon
    (Public Library of Science, 2014) Wonkam, Ambroise; Bitoungui, Valentina J Ngo; Vorster, Anna A; Ramesar, Raj; Cooper, Richard S; Tayo, Bamidele; Lettre, Guillaume; Ngogang, Jeanne
    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.
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    Sickle cell anaemia in Cameroon : co-inheritance of α-thalassemia, HBB gene haplotypes, clinical & haematological characterisations
    (2015) Rumaney, Maryam; Wonkam, Ambroise; Vorster, Anna A; Ramesar, Rajkumar
    Background: Although sickle cell anaemia (SCA) is genetically characterised by a single point mutation, patients can manifest varying degrees of clinical severity due to various genetic modulators that affect the phenotype of this disease. The co-inheritance of alpha-thalassemia (α-thalassemia) has been associated with a milder phenotype in SCA patients (e.g. lower stoke rate), but could also result in the increase of vaso-occlusive (VOC) pain episodes. There is a scarcity of data on the co-inheritance of α-thalassemia and SCA in Cameroon. The present study explored the correlation between α-thalassemia, haematological indices, and clinical events in Cameroonian SCA patients. Materials and Methods: For this cross-sectional study, a full blood count and clinical phenotype profile was collected for 262 Cameroonian individuals. Restriction fragment length polymorphism - polymerase chain reaction (RFLP-PCR) was performed for the molecular diagnosis of SCA and for the study of the β-globin (HBB) gene cluster haplotypes. Multiplex Gap-PCR was performed to investigate the 3.7kb and 4.2kb α-thalassemia gene deletions.