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Published ahead of print on August 15, 2002, doi:10.1164/rccm.200202-155OC

Am. J. Respir. Crit. Care Med., Volume 167, Number 3, February 2003, 390-394

A more recent version of this article appeared on February 1, 2003
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Submitted on February 26, 2002
Accepted on August 11, 2002

Endothelial Nitric Oxide Synthase Variants in Cystic Fibrosis Lung Disease

Hartmut Grasemann1*, Karin Storm van's Gravesande2, Rainer Buscher1, Nikola Knauer1, Eric S Silverman2, Lyle J Palmer3, Jeffrey M Drazen2, and Felix Ratjen1

1 University of Essen, Children's Hospital, Essen, Germany, 2 Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA, 3 Channing Laboratory, Brigham and Women's Hospital, Boston, MA, USA; Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA

* To whom correspondence should be addressed. E-mail: hartmutg{at}hotmail.com.

Variants in the genes encoding for the nitric oxide synthases may act as disease modifier loci in cystic fibrosis, affecting both an individual's nitric oxide level and pulmonary function. In the present study, the 894G/T variant in exon 7 of the endothelial nitric oxide synthase gene was related to exhaled nitric oxide and pulmonary function in 70 cystic fibrosis patients aged 14.8±6.9 years (mean±standard deviation), with a mean forced expiratory volume in one second of 69.4±24.8 % predicted. While there was no association between endothelial nitric oxide synthase genotypes and exhaled nitric oxide in males, nitric oxide levels were significantly higher in female cystic fibrosis patients with a 894T mutant allele, compared to female patients homozygous for the 894G wild-type allele (7.0±4.4 ppb vs. 3.6±1.9 ppb, p = 0.02). Furthermore, in female patients, colonization of airways with Pseudomonas aeruginosa was significantly (p < 0.05) less frequent when carrying a 894T mutant allele as compared to wildtype. These data suggest that the 894T variant the endothelial nitric oxide synthase gene is associated with increased airway nitric oxide formation in female CF patients, possibly affecting colonization of airways with Pseudomonas aeruginosa.
Key words: exhaled NO, pulmonary function, P. aeruginosa, association study




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