Nitric Oxide Synthase 2 Promoter Polymorphism Is a Risk Factor for Allergic Asthma in Children.

Joanna Nowakowska,Aleksandra Szczepankiewicz,Paulina Sobkowiak,Irena Wojsyk-Banaszak,Anna Bręborowicz,Magdalena Mrówczyńska

doi:10.3390/medicina57121341

Joanna Nowakowska, Aleksandra Szczepankiewicz + Show 4 more

Open Access

https://doi.org/10.3390/medicina57121341

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Abstract

Background and Objectives: In paediatric population, atopic asthma is associated with increased eosinophil counts in patients, that correlate with the airway inflammation measured by the concentration of nitric oxide in exhaled air (FeNO). As the FeNO level is a biomarker of atopic asthma, we assumed that polymorphisms in nitric synthases genes may represent a risk factor for asthma development. The purpose of this study was to analyse the association of NOS genetic variants with childhood asthma in the Polish population. Materials and methods: In study we included 443 children—220 patients diagnosed with atopic asthma and 223 healthy control subjects. We have genotyped 4 single nucleotide polymorphisms (SNP) from 3 genes involved in the nitric oxide synthesis (NOS1, NOS2 and NOS3). All analyses were performed using polymerase chain reaction with restriction fragments length polymorphism (PCR-RFLP). Results: We observed significant differences between cases and controls in SNP rs10459953 in NOS2 gene, considering both genotypes (p = 0.001) and alleles (p = 0.0006). The other analyzed polymorphisms did not show association with disease. Conclusions: According to our results, 5′UTR variant within NOS2 isoform may have an impact of asthma susceptibility in the population of Polish children. Further functional studies are required to understand the role of iNOS polymorphism in NOS2 translation and to consider it as a novel risk factor in childhood asthma. The next step would be to apply this knowledge to improve diagnosis and develop novel personalized asthma therapies.

Highlights

Asthma is a heterogeneous disease characterized by chronic airway inflammation, variable airflow limitation and airway hyperresponsiveness
In this case-control study we investigated a possible association of the single nucleotide polymorphisms (SNPs) in all three NO synthases (NOSs) genes with IgE-mediated childhood asthma and fractionated exhaled nitric oxide (FeNO) levels
Genotyping: We have genotyped 4 SNPs from 3 genes involved in the nitric oxide synthesis (NOS1, NOS2 and NOS3)

Summary

Introduction

Asthma is a heterogeneous disease characterized by chronic airway inflammation, variable airflow limitation and airway hyperresponsiveness. Type of airway inflammation differs between asthmatic patients, but in childhood asthma up to 80% of patients demonstrates T helper cells subtype 2 (Th2)-mediated allergic inflammation with overexpression of Th2 cytokines (e.g., IL-4, IL-5 and IL-13), increased IgE production and enhanced recruitment of eosinophils to the site of inflammation in the airways [1] In these cases, asthma is frequently associated with atopic dermatitis and rhinitis [2,3]. The aim of our study was to determine whether the previously reported associations of NOS variants with asthma are observed in Polish asthmatic children In this case-control study we investigated a possible association of the single nucleotide polymorphisms (SNPs) in all three NOS genes with IgE-mediated childhood asthma and FeNO levels. Atopic asthma is associated with increased eosinophil counts in patients, that correlate with the airway inflammation measured by the concentration of nitric oxide in exhaled air (FeNO). The step would be to apply this knowledge to improve diagnosis and develop novel personalized asthma therapies

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