6q12 and 11p14 variants are associated with postnatal exhaled nitric oxide and respiratory symptoms

Publication date: Available online 19 January 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Oliver Fuchs, Olga Gorlanova, Philipp Latzin, Anne Schmidt, Maximilian Schieck, Antoaneta A. Toncheva, Sven Michel, Vincent D. Gaertner, Michael Kabesch, Urs Frey
BackgroundExhaled nitric oxide (eNO) is a biomarker of airway inflammation and seems to precede respiratory symptoms, such as asthma in childhood. Identifying genetic determinants of postnatal eNO may aid in unraveling the role of eNO in epithelial function or airway inflammation and disease.ObjectiveTo identify genetic determinants of early postnatal eNO and subsequent respiratory symptoms during the first year of life.MethodsWithin a population-based birth cohort, eNO was measured in healthy term infants aged 5 weeks during quiet tidal breathing in unsedated sleep. We assessed associations of single-nucleotide polymorphisms with eNO in a genome-wide association study, and subsequent symptoms of lower respiratory tract infections during the first year of life; and asked if this was modified by prenatal and early-life environmental factors.ResultsWe identified so far unknown determinants of infant eNO: rs208515 (p=3.3 x 10^-8) located at 6q12, probably acting in "trans", and explaining 10.3% of eNO variance; and furthermore rs1441519 (p=1.6 x 10^-6) at 11p14, potentially impacting NO synthase 3 (NOS3) expression as shown by in-vitro functional analyses. Moreover, the 6q12 locus was inversely associated with subsequent respiratory symptoms (p<0.05) and time to recovery after first respiratory symptoms during the first year of life (p<0.05).ConclusionThe identification of novel genetic determinants of infant eNO may implicate that postnatal eNO metabolism in healthy infants prior to first viral infections and sensitization is related to mechanisms other than those associated with asthma, atopy or increased risk thereof later in life.

Teaser

The identification of novel genetic determinants of infant eNO, at previously unknown loci 6q12 and 11p14, may implicate that postnatal eNO metabolism in healthy infants prior to first viral infections and sensitization is related to mechanisms other than those associated with asthma, atopy or increased risk thereof later in life.


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