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一氧化氮合酶 2 启动子多态性是儿童过敏性哮喘的危险因素。

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

机构信息

Molecular and Cell Biology Unit, Poznan University of Medical Sciences, 60-572 Poznan, Poland.

Department of Pediatric Pulmonology, Allergy and Clinical Immunology, Poznan University of Medical Sciences, 60-572 Poznan, Poland.

出版信息

Medicina (Kaunas). 2021 Dec 8;57(12):1341. doi: 10.3390/medicina57121341.

Abstract

: 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 genetic variants with childhood asthma in the Polish population. : 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 (, and ). All analyses were performed using polymerase chain reaction with restriction fragments length polymorphism (PCR-RFLP). We observed significant differences between cases and controls in SNP rs10459953 in gene, considering both genotypes ( = 0.001) and alleles ( = 0.0006). The other analyzed polymorphisms did not show association with disease. : According to our results, 5'UTR variant within 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 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.

摘要

在儿科人群中,特应性哮喘与患者嗜酸性粒细胞计数增加有关,嗜酸性粒细胞计数与呼出气一氧化氮(FeNO)浓度所测量的气道炎症相关。由于 FeNO 水平是特应性哮喘的生物标志物,我们假设一氧化氮合酶基因的多态性可能是哮喘发展的一个危险因素。本研究的目的是分析遗传变异与波兰人群儿童哮喘之间的关系。

在研究中,我们纳入了 443 名儿童-220 名被诊断为特应性哮喘的患者和 223 名健康对照者。我们对涉及一氧化氮合成的 3 个基因中的 4 个单核苷酸多态性(SNP)进行了基因分型( 、 和 )。所有分析均使用聚合酶链反应与限制性片段长度多态性(PCR-RFLP)进行。

我们观察到 SNP rs10459953 在 基因中的基因型( = 0.001)和等位基因( = 0.0006)之间存在显著差异。考虑到所有病例和对照组,我们观察到 SNP rs10459953 在 基因中的基因型( = 0.001)和等位基因( = 0.0006)之间存在显著差异。其他分析的多态性与疾病无关联。

根据我们的结果, 同工型的 5'UTR 变体可能对波兰儿童人群的哮喘易感性有影响。需要进一步的功能研究来了解 iNOS 多态性在 翻译中的作用,并将其视为儿童哮喘的一个新的危险因素。下一步是应用这一知识来改善诊断并开发新的个性化哮喘治疗方法。

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