Associations between nitric oxide synthase genes and exhaled NO-related phenotypes according to asthma status.Report as inadecuate

Associations between nitric oxide synthase genes and exhaled NO-related phenotypes according to asthma status. - Download this document for free, or read online. Document in PDF available to download.

* Corresponding author 1 CEPH - Centre d-Etude du Polymorphisme Humain 2 Variabilité Génétique et Maladies Humaines 3 IUH - Institut Universitaire d-Hématologie 4 CESP - Centre de recherche en épidémiologie et santé des populations 5 Service d-explorations fonctionnelles respiratoires Lille 6 Département pneumologie et addictologie Montpellier 7 Institut d-oncologie-développement Albert Bonniot de Grenoble 8 Département de pédiatrie 9 CNG - Centre National de Génotypage

Abstract : BACKGROUND: The nitric oxide NO pathway is involved in asthma, and eosinophils participate in the regulation of the NO pool in pulmonary tissues. We investigated associations between single nucleotide polymorphisms SNPs of NO synthase genes NOS and biological NO-related phenotypes measured in two compartments exhaled breath condensate and plasma and blood eosinophil counts. METHODOLOGY: SNPs N = 121 belonging to NOS1, NOS2 and NOS3 genes were genotyped in 1277 adults from the French Epidemiological study on the Genetics and Environment of Asthma EGEA. Association analyses were conducted on four quantitative phenotypes: the exhaled fraction of NO FeNO, plasma and exhaled breath condensate EBC nitrite-nitrate levels NO2-NO3 and blood eosinophils in asthmatics and non-asthmatics separately. Genetic heterogeneity of these phenotypes between asthmatics and non-asthmatics was also investigated. PRINCIPAL FINDINGS: In non-asthmatics, after correction for multiple comparisons, we found significant associations of FeNO levels with three SNPs in NOS3 and NOS2 P ≤ 0.002, and of EBC NO2-NO3 level with NOS2 P = 0.002. In asthmatics, a single significant association was detected between FeNO levels and one SNP in NOS3 P = 0.004. Moreover, there was significant heterogeneity of NOS3 SNP effect on FeNO between asthmatics and non-asthmatics P = 0.0002 to 0.005. No significant association was found between any SNP and NO2-NO3 plasma levels or blood eosinophil counts. CONCLUSIONS: Variants in NO synthase genes influence FeNO and EBC NO2-NO3 levels in adults. These genetic determinants differ according to asthma status. Significant associations were only detected for exhaled phenotypes, highlighting the critical relevance to have access to specific phenotypes measured in relevant biological fluid.

Author: Emmanuelle Bouzigon - Florent Monier - Mekki Boussaha - Nicole Le Moual - Hélène Huyvaert - Régis Matran - Sébastien Letort -



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