Jessica Bruggen

Iron is an essential nutrient that is involved in many important processes in the human body. Iron can be found in a number of compounds including the cytosolic iron storage protein, ferritin. Iron availability in the body must be tightly regulated because high levels of free iron can create harmful reactive oxygen species. Ferritin is integral to managing excess iron in cells. Conversely, under conditions of iron deficiency, ferritin releases its iron content via ferritinophagy, and this process is mediated by nuclear receptor coactivator 4 (NCOA4). Thus, NCOA4 may play an important role in the maintenance of systemic iron homeostasis via ferritinophagy. Reduced ferritinophagy may result in excessive iron sequestration that is then unavailable for the body to use. African iron overload is a unique condition where patients present mild anemia despite systemic iron overload. Recently, mice with the loss of Ncoa4 were characterized to have a phenotype recapitulating African iron overload. Thus, we investigated if a particular genotype of NCOA4 is present in the African population, which may potentially contribute to the development of African iron overload. By screening a genome database, we found a genetic variant of NCOA4 specific to Africans, and tested if this can be detected in genomic DNA samples from Ugandans using a novel qPCR-based approach. The genetic variant in question has been computationally predicted to have pathophysiological implications, which would be associated with modulated ferritinophagy and the status of the systemic iron pool.