Methodologic and analytic advances in molecular genetics

identify many disease-predisposing variants in the human genome.

One of the challenges presented by these studies is to

define the mechanisms by which a given genetic variant affects

a pathophysiologic disorder. This inevitable quandary confronts

previously reported that a genetic polymorphism of

chromatogranin A (CHGA), a soluble protein released from

secretory granules of chromaffin cells and sympathetic nerves,

predicts hypertensive ESRD in black patients. Using population

stimulates endothelin release from endothelial cells. In view of

the major role for endothelin postulated in the pathogenesis of

a variety of cardiovascular and renal diseases, the authors questioned

whether endothelin secretion is the mechanistic link

between CHGA and renal dysfunction.