Exhaled nitric oxide in patients with asthma: association with NOS1 genotype

Am J Respir Crit Care Med. 2000 Dec;162(6):2043-7. doi: 10.1164/ajrccm.162.6.2003089.


An increased concentration of nitric oxide (NO) in exhaled air (FENO) is now recognized as a critical component of the asthmatic phenotype. When we identified patients with asthma on the basis of a standard case definition alone, we found that they were remarkably heterogeneous with respect to their FENO. However, when we included genotype at a prominent asthma candidate gene (i.e., NOS1) in the case definition, and determined the number of AAT repeats in intron 20, we identified a remarkably homogeneous cohort of patients with respect to FENO. Both mean FENO (p = 0.00008) and variability around the mean (p = 0.000002) were significantly lower in asthmatic individuals with a high number (> or = 12) of AAT repeats at this locus than in those with fewer repeats. These data provide a biologically tenable link between genotype at a candidate gene in a region of linkage, NOS1, and an important component of the asthmatic phenotype, FENO. We show that addition of NOS1 genotype to the case definition of asthma allows the identification of a uniform cohort of patients, with respect to FENO, that would have been indistinguishable by other physiologic criteria. Our isolation of this homogeneous cohort of patients ties together the well-established associations among asthma, increased concentrations of NO in the exhaled air of asthmatic individuals, and variations of trinucleotide repeat sequences as identified in several neurologic conditions.

Publication types

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

MeSH terms

  • Adult
  • Asthma / genetics
  • Asthma / physiopathology*
  • Base Sequence
  • Cohort Studies
  • DNA / genetics
  • Female
  • Gene Frequency / genetics
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics*
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase / genetics*
  • Nitric Oxide Synthase Type I
  • Phenotype
  • Statistics, Nonparametric


  • Nerve Tissue Proteins
  • Nitric Oxide
  • DNA
  • NOS1 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I