A smoking-dependent risk of coronary artery disease associated with a polymorphism of the endothelial nitric oxide synthase gene

Nat Med. 1996 Jan;2(1):41-5. doi: 10.1038/nm0196-41.


Endothelium-dependent vasodilatation is mediated by release of nitric oxide formed by constitutively expressed endothelial nitric oxide synthase (ecNOS). We explored the distribution of polymorphism ecNOS4a/b in 549 subjects with, and 153 without, coronary artery disease in relation to smoking. In current and ex-cigarette smokers, but not nonsmokers, there was a significant excess of homozygotes for the rare ecNOS4a allele in patients with severely stenosed arteries, compared with those with no or mild stenosis. This genotype was also associated with a history of myocardial infarction. This smoking-dependent excess coronary risk in ecNOS4a homozygotes is consistent with predisposition to endothelial dysfunction.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Base Sequence
  • Cohort Studies
  • Coronary Disease / epidemiology*
  • Coronary Disease / genetics*
  • DNA Primers
  • Endothelium, Vascular / enzymology*
  • Female
  • Genotype
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / genetics*
  • Nitric Oxide Synthase / genetics*
  • Pedigree
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Reference Values
  • Risk Factors
  • Smoking / adverse effects*
  • Smoking Cessation*


  • DNA Primers
  • Nitric Oxide Synthase