Pharmacogenetic relevance of endothelial nitric oxide synthase polymorphisms and gene interactions

Abstract

Endothelial nitric oxide synthase (NOS3) is a key enzyme responsible for nitric oxide (NO) generation in the vascular endothelium. Endothelial dysfunction is characterized by reduced NO production, and is a hallmark of cardiovascular diseases. Drugs with cardiovascular action may activate NOS3 and result in NO release and vasodilation. Moreover, genetic variations affect NOS3 expression and activity, and may partially explain the variability in the responses to cardiovascular drugs. We reviewed NO signaling and genetic effects on NO formation, and the effects of NOS3 polymorphisms, haplotypes and gene–gene interactions within NO signaling pathways on the responses to cardiovascular drugs. We discuss the role of rare NOS3 variants and further gene–gene interactions analysis for the development of novel therapies for cardiovascular diseases.