Association of Variants at <i>BCL11A</i> and <i>HBS1L-MYB</i> with Hemoglobin F and Hospitalization Rates among Sickle Cell Patients in Cameroon

<div><p>Background</p><p>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.</p><p>Methods and Findings</p><p>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 <i>HBB</i> 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 <i>BCL11A</i> 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 <i>HBS1L-MYB</i> region (<i>HMIP</i>) likewise had a significant impact on HbF, however, we did not find an association between HbF and the variations in <i>HBB</i> cluster and <i>OR51B5/6</i> 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 <i>HBS1L-MYB</i> region (<i>HMIP</i>) and <i>BCL11A</i> affect both other hematological indices and rates of hospitalization.</p><p>Conclusions</p><p>This study has confirmed the associations of SNPs in <i>BCL11A</i> and <i>HBS1L-MYB</i> and fetal haemoglobin in Cameroonian SCA patients; hematological indices and hospitalization rates were also associated with specific allelic variants.</p>