CYP2D6 Pharmacogenetics in Nigerian Sickle Cell Disease: Phase 1 of Implementing Pharmacogenomics Testing for Effective Care and Treatment in Africa (iPROTECTA) program.

Background: Sickle Cell Disease (SCD) is highly prevalent in Nigeria, with severe pain crises being a primary cause of morbidity. Codeine and tramadol are frequently used opioids, but their effectiveness and safety are significantly influenced by Methods: This prospective, multicenter implementation study recruited 503 consenting SCD patients (HbSS or HbSC) aged ≥15 years from five Nigerian sites. Blood samples were collected for DNA extraction. Results: We successfully genotyped 503 SCD patients with a mean age of 25.1 years, while 61.4% were female, and hydroxyurea use was less than 9.4%. Actionable Conclusions: This study successfully established a genotyped cohort of 503 Nigerian SCD patients, demonstrating the feasibility of pre-emptive pharmacogenetic testing through a Pan-African collaborative model in a resource-limited setting. The identification of PM and UM provides direct clinical guidance, as CPIC guidelines recommend avoiding codeine and tramadol in these groups due to the high risk of diminished efficacy or serious toxicity, respectively. The high prevalence of actionable CYP2D6 variants indicates a substantial proportion of Nigerian SCD patients may experience altered opioid responses, underscoring the need for tailored prescribing to optimise pain control and minimise adverse drug reactions.