Genetic and environmental effects on exhaled nitric oxide and airway responsiveness in a population-based sample of twins

¹ Dept of Respiratory Medicine, Rikshospitalet University Hospital, Oslo, Norway
² Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway

^* To whom correspondence should be addressed. E-mail: may.brit.lund{at}rikshospitalet.no.

	Abstract

Elevated levels of exhaled nitric oxide (eNO) and airway hyperresponsiveness are intermediates phenotypes of asthma.

Using population-based twins' data we estimated the relative contribution of genes, family environment and non-shared environmental influences to variation in eNO and airway responsiveness (AR). Secondly we investigated the genetic and environmental sources of co-variation between these two asthma-related phenotypes.

The study population comprised a random sample of 377 adult twins identified through the Norwegian Twin Registry. Main outcome variables were eNO and AR to methacholine.

Genetic effects accounted for 60% of the variation in eNO. Family environment explained 30% of the variation in AR, while non-shared environment explained the remaining variation for both measures. For both eNO and AR, there were significant regression effects of atopy and smoking. The association between eNO and AR (r=0.14, p=0.006) was primarily explained by common genetic factors. Subanalyses restricted to atopic and non smoking twins, strengthened the observation.

Variation in eNO and AR appears to be explained by different genetic and environmental variance structures. Variation in exhaled NO is explained by genetic and non-shared environmental effects, whereas an environmental model best explains variation in AR. Common genetic effects explain the small, but significant association between eNO and AR.