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Published ahead of print on January 16, 2003, doi:10.1164/rccm.200211-1342OC

Am. J. Respir. Crit. Care Med., Volume 167, Number 8, April 2003, 1113-1116

A more recent version of this article appeared on April 15, 2003
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Submitted on November 16, 2002
Accepted on January 14, 2003

Effects of gender and gene variants in constitutive nitric oxide synthases on exhaled nitric oxide

Hartmut Grasemann1*, Karin Storm van's Gravesande2, Rainer Buscher1, Jeffrey M Drazen2, and Felix Ratjen1

1 Pediatrics, University of Essen, Essen, Germany, 2 Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA

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

Genetic factors may contribute to the variability of exhaled nitric oxide in healthy individuals. We studied exhaled nitric oxide and genetic variants in both neuronal and endothelial nitric oxide synthase in 105 healthy non-smoking and smoking subjects. Genomic DNA was screen for a repeat polymorphism in intron twenty of the neuronal nitric oxide synthase gene and the 893G/T mutation of the endothelial nitric oxide synthase gene. Exhaled nitric oxide was significantly higher in males than females in both non-smokers (p < 0.0001) and smokers (p = 0.003). No association was found between exhaled nitric oxide and the variant in the endothelial nitric oxide synthase gene. However, healthy non-smoking females with larger repeat numbers (i.e. both alleles >= 12 repeats) in neuronal nitric oxide synthase had significantly lower nitric oxide levels than had females with small repeat numbers (i.e. at least one allele < 12 repeats) (13.6 ± 1.6 ppb vs. 19.4 ± 1.6 ppb, p = 0.02). No association was found between exhaled nitric oxide and neuronal nitric oxide synthase genotype in males. These data suggest that variants in the neuronal nitric oxide synthase gene contribute to the variability of airway nitric oxide concentrations in healthy females.
Key words: nitric oxide, polymorphism, sex factors




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