Abstract
Aims and Objectives: Exhaled nitric oxide (eNO) is a biomarker of airway inflammation and if elevated seems to precede respiratory symptoms early in life. We aimed at identifying genetic determinants of early postnatal eNO and their relation with subsequent respiratory symptoms.
Methods: In a population-based birth cohort, eNO was measured in healthy term infants aged 5 weeks during quiet tidal breathing in unsedated sleep. We assessed whether single nucleotid polymorphisms were associated with eNO in a genome-wide association study, whether this was associated with subsequent respiratory symptoms during the first year of life and if these associations were modified by environmental factors.
Results: We identified loci associated with infant eNO: rs208515 (p=3.3x10-8) at 6q12 upstream the human eyes shut homolog (EYS) gene, and rs1441519 (p=1.6 x 10-6) at 11p14 upstream the human anoctamin 3/mucin 15 (ANO3/MUC15) gene, both possibly related to the epithelial growth factor pathway with rs208515 explaining 13.3% of eNO variance. The 6q12 locus was negatively associated with subsequent symptoms with a relative risk of 0.80 (95%CI 0.68-0.95, p<0.01) and recovery time after first viral infection (p<0.02). Associations were not modified by assessed environmental factors.
Conclusions: This study identified novel genetic determinants of infant eNO with possible functional significance in the region of genes associated with EGFR function. The identification of these genetic variants may raise the hypothesis that prior to first viral infections and postnatal sensitization eNO metabolism is stronger related to epithelial function and lung development.
- Copyright ©ERS 2015