Effects of sex and of gene variants in constitutive nitric oxide synthases on exhaled nitric oxide.
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.
Grasemann
Hartmut
H
Department of Pediatrics, University of Essen, Germany. hartmutg@hotmail.com
Storm van's Gravesande
Karin
K
Buscher
Rainer
R
Drazen
Jeffrey M
JM
Ratjen
Felix
F
D000293:Adolescent; D000328:Adult; D001944:Breath Tests; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D012737:Sex Factors
D009569:Nitric Oxide; C496320:NOS1 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III