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

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 (Fe(NO)), 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 Fe(NO) 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 Fe(NO) levels and one SNP in NOS3 (P = 0.004). Moreover, there was significant heterogeneity of NOS3 SNP effect on Fe(NO) 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 Fe(NO) 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.

SUBMITTER: Bouzigon E

PROVIDER: S-EPMC3348876 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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

Bouzigon Emmanuelle E Monier Florent F Boussaha Mekki M Le Moual Nicole N Huyvaert Hélène H Matran Régis R Letort Sébastien S Bousquet Jean J Pin Isabelle I Lathrop Mark M Kauffmann Francine F Demenais Florence F Nadif Rachel R

PloS one 20120509 5

<h4>Background</h4>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.<h4>Methodology</h4>SNPs (N = 121) belonging to NOS1, NOS2 and NOS3 genes were genotyped in 1277 adults from ...[more]

PMID: 22590587

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Project description:INTRODUCTION:Fractional exhaled nitric oxide (FENO) is a biomarker of airway inflammation in asthma. The measurement of FENO is utilized to assist in the diagnosis and treatment of children with asthma, especially for those treated with inhaled corticosteroids. OBJECTIVES:The aims of this study were to evaluate the correlations between FENO and atopic status, blood eosinophil levels, FCER2 mutation, and asthma control in Vietnamese children. SUBJECTS AND METHODS:This was a prospective and descriptive study approved by the local Ethical Board. All children with uncontrolled asthma, seen in the National Hospital of Pediatrics (Hanoi, Vietnam), were included. Exhaled breath FENO, blood eosinophils, skin prick test, total IgE, asthma control test (ACT), and FCER2 gene polymorphism were performed at inclusion. They were followed up at 3 months to evaluate clinical status, FENO levels, and ACT. RESULTS:Forty-two children with uncontrolled asthma with a mean age of 10±3 years (6-16 years) were included. The male/female ratio was 2.5/1. The mean FENO levels were 26±25 ppb. FENO was significantly higher in patients with a positive skin prick test for respiratory allergens (P<0.05). FENO was significantly correlated with blood eosinophil levels (r=0.5217; P=0.0004). Five of the 32 subjects (15.6%) had a mutation of FCER2 gene (rs28364072 SNP). In this group, the levels of FENO were highest (37±10 ppb; P<0.05). The levels of FENO were significantly decreased after 3 months of treatment (17±8 ppb vs 26±25 ppb; P<0.05). Significant correlations between inhaled corticosteroid doses and FENO levels occurred at 1 and 3 months (r=0.415, P=0.007; r=0.396, P=0.010; respectively). There were no correlations between FENO levels, ACT, and daily use of salbutamol. After 3 months, asthma remained uncontrolled in 22.2% of children. CONCLUSION:The measurement of FENO levels is a useful and feasible tool to predict clinical, biological, and asthma control in Vietnamese children.

Dataset Information

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

Publications

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

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