Endothelial nitric oxide synthase variants in cystic fibrosis lung disease

H Grasemann, KSV Gravesande, R Buscher, N Knauer, ES Silverman, Lyle Palmer, JM Drazen, F Ratjen

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Abstract

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 this 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 who were aged 14.8 +/- 6.9 years (mean +/- SD), with a FEV1 of 69.4 +/- 24.8% predicted. Although 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 an 894T mutant allele, compared with female patients homozygous for the 894G wild-type allele (7.0 +/- 4.4 versus 3.6 +/- 1.9 parts per billion, p = 0.02). Furthermore, in female patients, colonization of airways with Pseudomonas aeruginosa was significantly (p <0.05) less frequent when carrying an 894T mutant allele as compared with wild type. These data suggest that the 894T variant in the endothelial nitric oxide synthase gene is associated with increased airway nitric oxide formation in female cystic fibrosis patients, possibly affecting colonization of airways with P. aeruginosa.
Original languageEnglish
Pages (from-to)390-394
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume167
DOIs
Publication statusPublished - 2003

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Grasemann, H., Gravesande, KSV., Buscher, R., Knauer, N., Silverman, ES., Palmer, L., ... Ratjen, F. (2003). Endothelial nitric oxide synthase variants in cystic fibrosis lung disease. American Journal of Respiratory and Critical Care Medicine, 167, 390-394. https://doi.org/10.1164/rccm.200202-155OC