Comprehensive Genetic and Phenotypic Analysis of Hemoglobinopathies in Multi-Ethnic Populations: Investigating the Clinical, Molecular, and Epidemiological Aspects of Sickle Cell Disease and Thalassemia

Background: Sickle cell disease (SCD) and thalassemia are prevalent inherited hemoglobinopathies with varying clinical severity.Genetic modifiers, such as alpha-thalassemia and fetal hemoglobin (HbF) levels, play a crucial role in influencing the clinical outcomes of these disorders.Objectives: To perform a comprehensive genetic and phenotypic analysis of SCD and thalassemia in a multiethnic cohort, exploring the impact of genetic mutations and modifiers on clinical severity.Methods: A cross-sectional study was conducted on 55 patients, including 30 with SCD and 25 with thalassemia.Clinical data were collected, and genetic analysis was performed to identify common mutations and genetic modifiers, such as alpha-thalassemia and HbF levels.Statistical analyses were conducted to assess the relationships between genetic factors and clinical outcomes.Results: In SCD, 85% of patients were homozygous for HbSS, with 25% also having alphathalassemia and 40% exhibiting elevated HbF levels (>15%).These modifiers were associated with milder disease, fewer vaso-occlusive crises, and higher hemoglobin levels (mean 9.1 g/dL).Thalassemia patients with 0 mutations experienced severe anemia (hemoglobin <7 g/dL) and were transfusion-dependent, while those with + mutations had moderate anemia and required less frequent transfusions. Conclusion:The study highlights the significant role of genetic modifiers in determining the severity of SCD and thalassemia.Alpha-thalassemia and elevated HbF levels were associated with improved clinical outcomes in SCD, while the type of beta-globin mutation influenced the severity of thalassemia.Understanding these modifiers is crucial for genotype-guided management and personalized treatment strategies.