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Am. J. Respir. Crit. Care Med., Volume 162, Number 6, December 2000, 2172-2176

Airway Nitric Oxide Levels in Cystic Fibrosis Patients Are Related to a Polymorphism in the Neuronal Nitric Oxide Synthase Gene

HARTMUT GRASEMANN, NICOLA KNAUER, RAINER BÜSCHER, KARIN HÜBNER, JEFFREY M. DRAZEN, and FELIX RATJEN

Children's Hospital and Ruhrlandklinik, University of Essen, Essen, Germany; and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

Patients with cystic fibrosis (CF) have decreased concentrations of expired nitric oxide (FENO) as compared with healthy individuals. A number of factors, including viscous mucus as a diffusion barrier for airway NO, consumption of NO by bacterial enzymes, and decreased NO production have been hypothesized to account for these low levels of FENO. We examined the relationship 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 = 0.027) lower in CF patients who harbored two alleles with a high number of repeats (>=  12) than in those who harbored alleles with fewer 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 significantly (p = 0.0358) more common in CF patients with high numbers of AAT repeats in the NOS1 gene. Significant differences between NOS1 genotypes were also observed among patients homozygous for the cystic fibrosis transmembrane 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 airways with P. aeruginosa (p = 0.0147) and Aspergillus fumigatus (p = 0.0221). These data provide evidence that the NOS1 gene is not only associated with the variability of FENO, but also with P. aeruginosa colonization of airways in CF patients.




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