Therapeutic implications of human endothelial nitric oxide synthase gene polymorphism.
Vascular endothelial dysfunction is now recognized as a common phenomenon in an array of cardiovascular disorders. Production of nitric oxide via the endothelial isoform of nitric oxide synthase [eNOS (previously termed NOS3 or ecNOS)] is vital for a healthy endothelium; several polymorphic variations of the gene encoding eNOS (NOS3) are now known and have been investigated with respect to disease risk. Surprisingly, only approximately half of these studies have demonstrated significant associations between NOS3 polymorphisms and cardiovascular disease, and many reports are contradictory. Central issues include adequate statistical power, appropriateness of control cohorts, multigene interactions and plausible biological consequences. So far, the inconsistencies are not unique to the NOS3 polymorphisms, but probably represent the broad challenges in defining genetic aspects of complex disease processes.
Wattanapitayakul
S K
SK
Dept of Pharmacology, Faculty of Medicine, Srinakharinwirot University, Sukhumvit 23, Bangkok 10110, Thailand.
Mihm
M J
MJ
Young
A P
AP
Bauer
J A
JA
D001120:Arginine / Q000494:pharmacology / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000235:genetics*; D005091:Exons / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D020030:Nitric Oxide Donors / Q000494:pharmacology / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D011110:Polymorphism, Genetic / Q000235:genetics*
D020030:Nitric Oxide Donors; D001120:Arginine; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III