Genetic effects of inflammation markers on exhaled nitric oxide in
schoolchildren with asthma: A twin study
Abstract
Background: Exhaled nitric oxide and blood eosinophils are clinical
asthma type 2 markers in use. Immunoglobulin E (IgE) is often involved
in the inflammation associated with atopic asthma. The effect of both
blood eosinophils and allergen-specific IgE on exhaled nitric oxide
levels is not completely understood. Twin-design studies can improve
understanding of the underlying contribution of genetically and/or
environmentally driven inflammation markers in asthma. Our aim was to
disentangle the covariance between asthma and exhaled nitric oxide into
genetic and environmental contributions that can account for
inflammation markers in a paediatric population. Methods: This
population-based, cross-sectional twin study enrolled 612 monozygotic
(MZ) and same-sex dizygotic (DZ) schoolchildren. Multivariate structural
equation modelling was utilized to separate the covariance between
asthma and exhaled nitric oxide into genetic and/or environmental
effects, taking allergen-specific IgE level and blood eosinophil count
into account while controlling for confounding factors. Results: The
cross-twin/cross-trait correlations had a higher magnitude in the MZ
twins than in the DZ twins indicating that genes affect the association.
The likelihood ratio test for model fitting resulted in the AE model as
the most parsimonious. A majority, 73%, of the phenotypic correlation
between asthma and exhaled nitric oxide, r=0.19 (0.05–0.33), was
attributable to genetic effects which mainly was due to the
allergen-specific IgE level. Conclusions: This study indicate that the
association between asthma - exhaled nitric oxide in children is to a
large extent explained by genetics via allergen-specific IgE-level but
not blood eosinophils. This might partly explain the clinical
heterogeneity in this group. A next step could be to include
allergen-specific IgE level in multivariate omic-studies.