This Article Full Text Full Text (PDF) All Versions of this Article: 200211-1342OCv1 167/8/1113    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Grasemann, H. Articles by Ratjen, F. Search for Related Content PubMed PubMed Citation Articles by Grasemann, H. Articles by Ratjen, F.

Effects of Sex and of Gene Variants in Constitutive Nitric Oxide Synthases on Exhaled Nitric Oxide

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

Correspondence and requests for reprints should be addressed to Hartmut Grasemann, M.D., Children's Hospital, University of Essen, Hufeland Strasse 55, D-45122 Essen, Germany. 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 synthases in 105 healthy nonsmoking and smoking subjects. Genomic DNA was screened for a repeat polymorphism in intron 20 of the neuronal nitric oxide synthase gene and for the 894G/T mutation of the endothelial nitric oxide synthase gene. Exhaled nitric oxide was significantly higher in males than females among both nonsmokers (p < 0.0001) and smokers (p = 0.003). No association was found between exhaled nitric oxide and the endothelial nitric oxide synthase gene variant. However, healthy nonsmoking females with greater numbers of repeats (i.e., both alleles with 12 or more repeats) in neuronal nitric oxide synthase had significantly lower nitric oxide levels than did females with fewer numbers of repeats (i.e., at least one allele with fewer than 12 repeats) (13.6 ± 1.6 versus 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

This article has been cited by other articles:

				J. Travers, S. Marsh, S. Aldington, M. Williams, P. Shirtcliffe, A. Pritchard, M. Weatherall, and R. Beasley Reference Ranges for Exhaled Nitric Oxide Derived from a Random Community Survey of Adults Am. J. Respir. Crit. Care Med., August 1, 2007; 176(3): 238 - 242. [Abstract] [Full Text] [PDF]

				V. Suresh, J. D. Mih, and S. C. George Measurement of IL-13-Induced iNOS-Derived Gas Phase Nitric Oxide in Human Bronchial Epithelial Cells Am. J. Respir. Cell Mol. Biol., July 1, 2007; 37(1): 97 - 104. [Abstract] [Full Text] [PDF]

				A.-C. Olin, B. Bake, and K. Toren Fraction of Exhaled Nitric Oxide at 50 mL/s: Reference Values for Adult Lifelong Never-Smokers Chest, June 1, 2007; 131(6): 1852 - 1856. [Abstract] [Full Text] [PDF]

				A. Morea, M. Cameran, A. G. Rebuffi, D. Marzenta, O. Marangon, L. Picci, F. Zacchello, and M. Scarpa Gender-sensitive association of CFTR gene mutations and 5T allele emerging from a large survey on infertility Mol. Hum. Reprod., August 1, 2005; 11(8): 607 - 614. [Abstract] [Full Text] [PDF]

				ATS/ERS Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide, 2005 Am. J. Respir. Crit. Care Med., April 15, 2005; 171(8): 912 - 930. [Full Text] [PDF]

				P. J. Franklin, S. M. Stick, P. N. Le Souef, J. G. Ayres, and S. W. Turner Measuring Exhaled Nitric Oxide Levels in Adults: The Importance of Atopy and Airway Responsiveness Chest, November 1, 2004; 126(5): 1540 - 1545. [Abstract] [Full Text] [PDF]

				U. Frey, C. Kuehni, H. Roiha, M. Cernelc, B. Reinmann, J. H. Wildhaber, and G. L. Hall Maternal Atopic Disease Modifies Effects of Prenatal Risk Factors on Exhaled Nitric Oxide in Infants Am. J. Respir. Crit. Care Med., August 1, 2004; 170(3): 260 - 265. [Abstract] [Full Text] [PDF]

				P.J. Franklin, S.W. Turner, R.C. Mutch, and S.M. Stick Comparison of single-breath and tidal breathing exhaled nitric oxide levels in infants Eur. Respir. J., March 1, 2004; 23(3): 369 - 372. [Abstract] [Full Text] [PDF]

				M. J. Tobin Asthma, Airway Biology, and Nasal Disorders in AJRCCM 2003 Am. J. Respir. Crit. Care Med., January 15, 2004; 169(2): 265 - 276. [Full Text] [PDF]