Alpha Globin Gene Copy Number Is Associated With Kidney Disease Among Black Individuals

Introduction: In addition to forming hemoglobin in red blood cells, alpha globin (HBA) has non-erythroid effects and is expressed in vascular endothelial cells where it interacts with endothelial nitric oxide (NO) synthase (eNOS) to limit nitric oxide diffusion across the myoendothelial junction. Reduced expression of HBA or disruption of HBA/eNOS interactions increases endothelial nitric oxide signaling. Humans have 0 to 3 copies of HBA per chromosome and Black individuals have increased variation in HBA allele count. Moreover, Black individuals are more likely to develop end-stage kidney disease (ESKD) and unexplained genetic factors may contribute to racial disparities in kidney disease not attributable to socioeconomic factors. Given that decreased endothelial NO signaling accelerates renal disease in mouse models, we hypothesized that lower HBA gene copy number would be associated with lower risk of kidney disease among Black individuals.