Lund M B, Kongerud J, Nystad W, Boe J, Harris J R
Department of Respiratory Medicine, Rikshospitalet University Hospital, N-0027 Oslo, Norway.
Eur Respir J. 2007 Feb;29(2):292-8. doi: 10.1183/09031936.00044805. Epub 2006 Nov 1.
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.
呼出一氧化氮（eNO）水平升高和气道高反应性是哮喘的中间表型。利用从双胞胎样本中收集的基于人群的数据，本文作者估计了基因、家庭环境和非共享环境影响对eNO和气道反应性（AR）变异的相对贡献。此外，还研究了这两种与哮喘相关表型之间协变的遗传和环境来源。研究人群包括通过挪威双胞胎登记处确定的377名成年双胞胎的随机样本。主要结局变量是eNO和对乙酰甲胆碱的AR。基因效应占eNO变异的60%。家庭环境占AR变异的30%，而非共享环境影响解释了这两种测量的其余变异。对于eNO和AR，特应性和吸烟均有显著的回归效应。eNO和AR之间虽小但显著的关联主要由遗传因素解释。限于特应性和不吸烟双胞胎的亚分析强化了这一观察结果。总之，呼出一氧化氮和气道反应性的变异似乎由不同的遗传和环境方差结构所解释。呼出一氧化氮的变异由遗传和非共享环境效应解释，而环境模型最能解释气道反应性的变异。共同的遗传效应解释了呼出一氧化氮和气道反应性之间虽小但显著的关联。
