Genomic and Phenotypic Profile of Sickle Cell Disease in Human Population in Cameroon

Sickle cell disease (SCD) is caused by a biallelic single nucleotide substitution in the beta-globin gene (HBB), resulting in an amino acid substitution, Glu7Val, formerly known as Glu6Val. An estimated 300,000 babies with SCD are born worldwide each year, with nearly 75% of these births being in sub-Saharan Africa. In Africa, at least 30-50% of children with untreated SCD die before the age of 5 years. Therefore, accelerating the path for novel therapies for SCD through genomics research on fetal hemoglobin (HbF) is critical. Variants in the currently known HbF‐modulating genes/loci, i.e., BCL11A, HBS1L-MYB, and XmnI-HBG2, explain only 10-20% of the variation of HbF levels in African individuals with SCD, compared with nearly 50% of the variation in HbF levels among Europeans. Expanding genomic research in populations of African ancestry could uncover the missing heritability of HbF-promoting loci. This study used the Human Heredity and Health (H3Africa) consortium SNP genotyping array developed from whole genome enriched for common variants in sub-Saharan Africans to investigate genomic variations associated with HbF levels in individuals with sickle cell anemia of the HbSS genotype from Cameroon. Two of the previously described loci, BCL11A and HBS1L-MYB were replicated, while a novel locus on chromosome 13 mapping to FLT1 was uncovered. The study therefore opens up a novel avenue for exploring SCD gene therapy.]]>
Cameroon SCD Informed ConsentThe study participants were recruited from five cities in Cameroon (Yaoundé, Douala, Bafoussam, Bertoua, and Maroua) between May 2016 and July 2018. Structured questionnaires were used to collect socio-demographic and clinical events from adult sickle cell disease (SCD) patients or parents/guardians of younger patients. Clinical features for the past 3 years were extracted from patient medical record. Only patients older than 5 years of age, who had not received a blood transfusion in the past 6 weeks were included. None was currently treated with hydroxycarbamide or opioids. The sampling strategy was not restricted to hospital-based patients to avoid the bias that might result from including only the sickest patients. To accomplish this goal, two SCD patient groups in Cameroon were engaged for collaboration and additional patients were recruited during their monthly meetings. No incentives were provided for participation in the study.]]>
Sampling and data collection: between May 2016 and July 2018Genotyping: 2018 and 2019Data analysis: 2021 to 2023]]>