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

Fuchs, Oliver; Gorlanova, Olga; Latzin, Philipp; Schmidt, Anne; Schieck, Maximilian; Toncheva, Antoaneta A; Michel, Sven; Gaertner, Vincent D; Kabesch, Michael; Frey, Urs (2017). 6q12 and 11p14 variants are associated with postnatal exhaled nitric oxide levels and respiratory symptoms. The Journal of allergy and clinical immunology, 140(4), pp. 1015-1023. Elsevier 10.1016/j.jaci.2016.11.048

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BACKGROUND Exhaled 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 levels might aid in unraveling the role of eNO in epithelial function or airway inflammation and disease. OBJECTIVE We sought to identify genetic determinants of early postnatal eNO levels and subsequent respiratory symptoms during the first year of life. METHODS Within a population-based birth cohort, eNO levels were measured in healthy term infants aged 5 weeks during quiet tidal breathing in unsedated sleep. We assessed associations of single nucleotide polymorphisms with eNO levels in a genome-wide association study and subsequent symptoms of lower respiratory tract infections during the first year of life and asked whether this was modified by prenatal and early-life environmental factors. RESULTS We identified thus far unknown determinants of infant eNO levels: rs208515 (P = 3.3 × 10-8), which is located at 6q12, probably acting in "trans" and explaining 10.3% of eNO level variance, and rs1441519 (P = 1.6 × 10-6), which is located at 11p14, potentially affecting nitric oxide synthase 3 (NOS3) expression, as shown by means of in vitro functional analyses. Moreover, the 6q12 locus was inversely associated with subsequent respiratory symptoms (P < .05) and time to recovery after first respiratory symptoms during the first year of life (P < .05). CONCLUSION The identification of novel genetic determinants of infant eNO levels might implicate that postnatal eNO metabolism in healthy infants before first viral infections and sensitization is related to mechanisms other than those associated with asthma, atopy, or increased risk thereof later in life.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Pneumologie (Pädiatrie)
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Paediatric Pneumology

UniBE Contributor:

Fuchs, Oliver and Latzin, Philipp

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1097-6825

Publisher:

Elsevier

Language:

English

Submitter:

Romy Melanie Rodriguez Del Rio

Date Deposited:

12 Feb 2018 13:08

Last Modified:

12 Feb 2018 13:08

Publisher DOI:

10.1016/j.jaci.2016.11.048

PubMed ID:

28109725

Uncontrolled Keywords:

Infants airway inflammation asthma exhaled nitric oxide genetics genome-wide association study wheeze

BORIS DOI:

10.7892/boris.109245

URI:

https://boris.unibe.ch/id/eprint/109245

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