Haplotype-Specific Genetic Epidemiology of Sickle Cell Anemia Patients in Accra, Ghana: Patterns, Clinical Implications, and Public Health Responses.

Abstract

Sickle cell disease (SCD) is a genetic disorder with a diverse spectrum of clinical presentation, often determined by inherited β^S gene haplotypes. Ghana, a country with a significant SCD burden, lacks population haplotype frequency data, hindering anthropological, genetic, and clinical understanding and management of the disease. A prospective sample of 191 SCD patients (sickle cell anemia; homozygous HbSS) was recruited at the Korle-Bu Teaching Hospital, Accra. Identification of β^S gene haplotypes was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Hematological tests were performed using routine laboratory procedures. Kruskal-Wallis ANOVA with Dunn post-hoc was used to compare the hematological parameters. Multinomial probability models were used to compare the frequencies of the observed haplotypes with those reported in other African countries. The Atypical haplotype was disproportionately prevalent (58%), followed by the Bantu/CAR (20%) and Benin (10%) haplotypes. Significant differences were observed between the haplotypes in lymphocyte count, platelet count, sodium and potassium levels (P < 0.001). In addition, disease severity varied significantly between haplotypes (P = 0.010), with notable differences between the Atypical and Bantu/CAR haplotypes (P_FDR = 0.020). Multinomial probability testing revealed a substantial deviation from the expected haplotype distribution, highlighting significant differences in haplotype frequencies between Ghana and other African countries. The Wright-Fisher model showed that the variation in Arab-Indian haplotype frequency reached zero by the 100^th generation. Our findings highlight the need to study haplotype composition in Ghana to identify population-specific risk factors and tailor public health interventions to better manage patient needs.