Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 168, Issue 2, Pages 228-231Publisher
AMER THORACIC SOC
DOI: 10.1164/rccm.200212-1491BC
Keywords
asthma; endothelial nitric oxide synthase; exhaled nitric oxide; polymorphism
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Funding
- NHLBI NIH HHS [HL-SCOR HL 56383-05] Funding Source: Medline
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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 (fraction of expired nitric oxide, FENO) in subjects with asthma. We identified a strong association between a known functional NOS3 missense sequence variant in the endothelial nitric oxide gene (G894T) and FENO level in a cohort of subjects with asthma. Age- and sex-adjusted FENO levels were lowest in asthmatic subjects with the TT genotype (geometric mean FENO [95% CI] = 7.17 [4.48 to 11.48] ppb) and were significantly higher in those with either the GT genotype (geometric mean FENO [95% CI] - 17.11 [13.80 to 21.23] ppb) or the GG genotype (geometric mean FENO [95% CI] 12.06 [9.91 to 14.67] ppb) (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.
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