PATHOPHYSIOLOGY OF LEG ULCERS IN SICKLE CELL DISEASE: THE ROLE OF GENETIC MODIFIERS – A SCOPING REVIEW PROTOCOL

Abstract

This scoping review aims to assess the literature on genetic modifiers of leg ulcers in sickle cell disease, evaluating available evidence, methodologies, and research gaps. A major morbidity in sickle cell disease is the development of leg ulcers. This clinical syndrome of SCD leg ulcers (SLU) has continued to be an enigma due to its multifactorial evolution, dearth of promising guidelines on treatment, and generally unsatisfactory response to treatment. Underlying genetic susceptibilities for SLU may impact counselling, prognostication, risk of development, severity as well as response to interventions. Hence the need for this scoping review. This scoping review will collate and assess studies in English on genetic markers of SLU among all SCD age groups, genders, races, and regions. Genetic or molecular markers to be assessed among patients with sickle cell leg ulcers included, genetic markers of Inflammation, vasculopathy, tissue damage, oxidative stress, coagulopathy as well as genetic predispositions that have been studied in relation to SLUs across all countries. This includes most common biomarkers that promote development of SLU, the single nucleotide polymorphic markers (SNPs) that work through the MAPK and SMAD signaling pathway. A PubMed search of all fields for literature published in English using the strategy (sickle cell) AND (leg ulcer), and (sickle cell) AND (leg ulcer genetics) from 1998 to 2023 (last 25 years) will be undertaken. This will be modified, according to the inclusion criteria, as appropriate across other databases. The other databases will include Google Scholar, web of Knowledge, Scopus, New Zealand Science, and Silver chair, Taylor and Francis + NEJM