This current observation of significant diversity in endothelin-1 polymorphism between African American sickle cell disease and control groups deserves further ex- amination. To do this, increasing the sample size and further characterization alongside specific clinical param- eters, disease stratification (severe versus mild) and sickle cell genetic haplotypes would provide a great benefit in elucidating their clinical and therapeutic implications in disease pathophysiology. Our report shows that endothelial nitric oxide synthase variants are less frequent with no significance among patients with sickle cell disease either in Africa20 or United States, while there is a potential role for endothelin-1 polymorphism in delineating clinical vari- ability or disease pathophysiology, not seen in Africa but in United States.