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Published ahead of print on May 8, 2003, doi:10.1164/rccm.200212-1491BC

Am. J. Respir. Crit. Care Med., Volume 168, Number 2, July 2003, 228-231

A more recent version of this article appeared on July 15, 2003
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Submitted on January 15, 2003
Accepted on May 1, 2003

The association of a missense mutation in the NOS3 gene with exhaled nitric oxide levels

Karin Storm van's Gravesande1, Michael E Wechsler1, Hartmut Grasemann2, Eric S Silverman1, Louis Le1, Lyle J Palmer3, and Jeffrey M Drazen1*

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

* To whom correspondence should be addressed. E-mail: jdrazen{at}nejm.org.

There is evidence that genetic factors affect nitric oxide formation and that sequence variants in the nitric oxide synthase genes contribute to the observed variance of nitric oxide levels in exhaled air (FENO) in asthmatic subjects. We identified a strong association between a known functional NOS missense sequence variant in the endothelial nitric oxide gene (G894T) and FENO level in a cohort of asthmatic subjects. Age and sex-adjusted FENO levels were lowest in asthmatics with the TT genotype ( geometric mean FENO [95%CI] =7.17 ppb [4.48 to 11.48]) and were significantly higher in those with either the GT ( geometric mean FENO [95%CI] =17.11 ppb [13.80 to 21.23]) or GG genotypes (geometric mean FENO [95%CI] =12.06 ppb [9.91 to 14.67]) (F2,59=5.97, p=0.004). The G894T DNA variant explained 16.3% of the residual variance in FENO levels. Our results demonstrate that the endothelial nitric oxide synthase, a nitric oxide synthase constitutively expressed in epithelial cells, plays an important role in determining measured levels of exhaled nitric oxide, a marker of the asthmatic condition.
Key words: asthma, exhaled nitric oxide, polymorphism




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