Abstract / Summary
Abstract: The main objective of this scoping review is to evaluate the availability, methodologies, quality, and research gaps in literature on genetic modifiers of leg ulcers in sickle cell disease (SCD). SCD leg ulcers (SLUs) are a major complication in SCD, with their multifactorial evolution and limited treatment guidelines posing significant challenges. Although genetic susceptibilities may eventually inform counseling and prognostication, current evidence remains exploratory and requires further validation. This study collates and assesses available research on genetic markers of SLUs across all age groups, sex, races, and regions. A comprehensive search of PubMed and other major databases, including Google Scholar, Web of Science, and Scopus, from 1998 to 2024, was performed. Findings highlight the need to complement clinical approaches with genetic insights to identify biomarkers critical for developing superior therapeutic interventions. Single-nucleotide polymorphic markers associated with the MAPK and small mothers against decapentaplegic signaling pathways emerged as the most common genetic factors influencing SLU development. Significantly, the review emphasizes the need for Africa, where the burden of SCD is highest, to expand research ownership through collaboration and investments in randomized control trials. Although the research terrain reflects economic disparities, strengthening local capacity could drive advancements in SLU management. In conclusion, integrating genetic knowledge into the management of SLUs is vital for improved outcomes, and addressing current research gaps is essential for guiding future evidence synthesis and interventions.