title: Genetic and environmental effects on exhaled nitric oxide and airway responsiveness in a population-based sample of twins.
abstract: Elevated levels of exhaled nitric oxide (eNO) and airway hyperresponsiveness are intermediate phenotypes of asthma. Using population-based data collected from a sample of twins, the present authors estimated the relative contribution of genes, family environment and nonshared environmental influences to variations in eNO and airway responsiveness (AR). In addition, the genetic and environmental sources of covariation between these two asthma-related phenotypes were investigated. The study population comprised a random sample of 377 adult twins identified through the Norwegian Twin Registry. The main outcome variables were eNO and AR to methacholine. Genetic effects accounted for 60% of the variation in eNO. Family environment accounted for 30% of the variation in AR, while nonshared environmental influences explained the remaining variation for both measures. For both eNO and AR, there were significant regression effects for atopy and smoking. The small, but significant association between eNO and AR was primarily explained by genetic factors. Sub-analyses restricted to atopic and nonsmoking twins strengthened the observation. In conclusion, variations in exhaled nitric oxide and airway responsiveness appear to be explained by different genetic and environmental variance structures. Variation in exhaled nitric oxide is explained by genetic and nonshared environmental effects, whereas an environmental model best explains the variation in airway responsiveness. Common genetic effects explain the small but significant association between exhaled nitric oxide and airway responsiveness.
authors.affiliation: Department of Respiratory Medicine, Rikshospitalet University Hospital, N-0027 Oslo, Norway. may.brit.lund@rikshospitalet.no
authors.forename: M B
authors.initials: MB
authors.lastname: Lund
authors.forename: J
authors.initials: J
authors.lastname: Kongerud
authors.forename: W
authors.initials: W
authors.lastname: Nystad
authors.forename: J
authors.initials: J
authors.lastname: Boe
authors.forename: J R
authors.initials: JR
authors.lastname: Harris
mesh_terms: D000328:Adult; D001980:Bronchi / Q000187:drug effects / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000235:genetics*; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D004777:Environment; D045853:Exhalation; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D009569:Nitric Oxide / Q000032:analysis*; D044465:White People / Q000235:genetics
chemical_list: D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D009569:Nitric Oxide