Exhaled nitric oxide in patients with asthma - Association with NOS1 genotype

An increased concentration of nitric oxide (NO) in exhaled air (FENO) is no w recognized as a critical component of the asthmatic phenotype. When we id entified patients with asthma on the basis of a standard case definition al one, we found that they were remarkably heterogeneous with respect to their FENO. However, when we included genotype at a prominent asthma candidate g ene (i.e., NOS1) in the case definition, and determined the number of AAT r epeats in intron 20, we identified a remarkably homogenous cohort of patien ts with respect to FENO. Both mean FENO (p = 0.00008) and variability aroun d the mean (p = 0.000002) were significantly lower in asthmatic individuals with a high number (greater than or equal to 12) of AAT repeats at this lo cus than in those with fewer repeats. These data provide a biologically ten able link between genotype at a candidate gene in a region of linkage, NOS1 , and an important component of the asthmatic phenotype, FENO. We show that addition of NOS1 genotype to the case definition of asthma allows the iden tification of a uniform cohort of patients, with respect to FENO, that woul d have been indistinguishable by other physiologic criteria. Our isolation of this homogenous cohort of patients ties together the well-established as sociations among asthma, increased concentrations of NO in the exhaled air of asthmatic individuals, and variations of trinucleotide repeat sequences as identified in several neurologic conditions.