Airway nitric oxide levels in cystic fibrosis patients are related to a polymorphism in the neuronal nitric oxide synthase gene

Patients with cystic fibrosis (CF) have decreased concentrations of expired nitric oxide (FENO) as compared with healthy individuals. A number of fact ors, including viscous mucus as a diffusion barrier for airway NO, consumpt ion of NO by bacterial enzymes, and decreased NO production have been hypot hesized to account for these low levels of FENO. We examined the relationsh ip between the size of an AAT repeat polymorphism in intron 20 of the NOS1 gene and FENO in 75 patients with CF. Mean FENO was significantly (p = 0.02 7) lower in CF patients who harbored two alleles with a high number of repe ats (greater than or equal to 12) than in those who harbored alleles with f ewer repeats at this locus (4.0 +/- 0.8 [mean +/- SEM] ppb versus 6.4 +/- 0 .9 ppb). Colonization of the airways with Pseudomonas aeruginosa was signif icantly (p = 0.0358) more common in CF patients with high numbers of AAT re peats in the NOS1 gene. Significant differences between NOS1 genotypes were also observed among patients homozygous for the cystic fibrosis transmembr ane regulator Delta F508 mutation for FENO (2.3 +/- 0.4 ppb versus 5.3 +/- 0.7 ppb, p = 0.0006), and this was also true for colonization of the airway s with P. aeruginosa (p = 0.0147) and Aspergillus fumigatus (p = 0.0221). T hese data provide evidence that the NOS1 gene is not only associated with t he variability of FENO, but also with P. aeruginosa colonization of airways in CF patients.