title: Clinical and pharmacogenetic impact of endothelial nitric oxide synthase polymorphisms on cardiovascular diseases.
abstract: Nitric oxide (NO) is a vasoactive substance synthesized from l-arginine by neuronal (NOS1), endothelial (NOS3), and inducible (NOS2) nitric oxide synthases. NOS3 is the most important NO synthase isoform in the vascular endothelium and therefore it exerts critical roles in the cardiovascular system. NOS3 is encoded by NOS3 gene, which displays a large number of genetic polymorphisms such as single nucleotide polymorphisms (SNPs), variable number of tandem repeats (VNTRs), microsatellites, and insertions/deletions. Interestingly, NOS3 regulation and NO production are affected by some NOS3 polymorphisms. Given these functional consequences and the protective role of NOS3 against cardiovascular diseases, many studies have investigated whether NOS3 polymorphisms affect the susceptibility to cardiovascular diseases and the responses to drugs that affect NOS3 activity in the cardiovascular system. In addition, a growing body of evidence shows the effects of combinations of NOS3 polymorphisms within haplotype blocks on NO bioavailability and disease susceptibility. In this review, we discuss the basic biochemical mechanisms of NOS3 regulation and the clinical and pharmacogenetic impact of NOS3 polymorphisms on cardiovascular diseases.
authors: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors: Gustavo H
authors: GH
authors: Oliveira-Paula
authors: Department of Psychiatric Nursing and Human Sciences, Ribeirao Preto College of Nursing, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
authors: Riccardo
authors: R
authors: Lacchini
authors: Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, Brazil. Electronic address: tanus@fmrp.usp.br.
authors: Jose E
authors: JE
authors: Tanus-Santos
mesh_terms: D002318:Cardiovascular Diseases / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D000071184:Pharmacogenomic Variants; D011110:Polymorphism, Genetic
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
keywords: Endothelial nitric oxide synthase; Genetic polymorphisms; Haplotypes; NOS3 gene; Nitric oxide; Pharmacogenetics