在患有哮喘的成年受试者中,FAM13AA和IL2RB基因中的SNPs与FeNO相关。

IF 3.7 4区 医学 Q1 BIOCHEMICAL RESEARCH METHODS Journal of breath research Pub Date : 2023-10-06 DOI:10.1088/1752-7163/acfbf1
Simone Accordini, Valentina Lando, Lucia Calciano, Cristina Bombieri, Giovanni Malerba, Antonino Margagliotti, Cosetta Minelli, James Potts, Diana A van der Plaat, Mario Olivieri
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引用次数: 0

摘要

一氧化氮作为气道功能的内源性调节剂和促炎介质在哮喘中具有不同的作用。部分呼出一氧化氮(FeNO)是一种可靠、定量、无创、简单、安全的评估哮喘气道炎症的生物标志物。先前的全基因组和遗传关联研究表明,不同的基因和单核苷酸多态性(SNPs)与FeNO有关。我们旨在鉴定哮喘中与FeNO相关的候选基因或基因区域中的SNPs。我们评估了264例哮喘病例(中位年龄42.8岁,女性47.7%),这些病例是在维罗纳(意大利;2008-2010年)的呼吸系统疾病基因-环境相互作用调查中在普通成年人群中发现的。代表50个候选基因的221个标签SNPs通过定制的GoldenGate基因分型分析进行基因分型。在不假设先验模型的情况下进行了两步关联分析:步骤(1)使用机器学习技术[梯度提升机(GBM)]来选择具有最高变量重要性测度的15个SNP;步骤(2)在线性回归模型中联合测试GBM选择的SNPs,以自然对数转换的FeNO作为正态分布结果,并以年龄、性别和SNPs作为协变量。我们在欧洲社区呼吸健康调查III的296名患者的独立样本中复制了我们的结果。我们发现,具有序列相似性的家族13成员A(FAM13A)中的SNP rs987314和白细胞介素2受体亚单位β(IL2RB)基因区中的SNPs rs3218258与成年哮喘受试者的FeNO显著相关。这些基因参与影响平滑肌收缩和内皮屏障功能反应(FAM13A)或免疫反应过程(IL2RB)的不同机制。我们的发现通过鉴定与气道炎症生物标志物相关的两个新的SNP,为目前对哮喘中FeNO的了解做出了贡献。
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SNPs inFAM13AandIL2RBgenes are associated with FeNO in adult subjects with asthma.

Nitric oxide has different roles in asthma as both an endogenous modulator of airway function and a pro-inflammatory mediator. Fractional exhaled nitric oxide (FeNO) is a reliable, quantitative, non-invasive, simple, and safe biomarker for assessing airways inflammation in asthma. Previous genome-wide and genetic association studies have shown that different genes and single nucleotide polymorphisms (SNPs) are linked to FeNO. We aimed at identifying SNPs in candidate genes or gene regions that are associated with FeNO in asthma. We evaluated 264 asthma cases (median age 42.8 years, female 47.7%) who had been identified in the general adult population within the Gene Environment Interactions in Respiratory Diseases survey in Verona (Italy; 2008-2010). Two hundred and twenty-one tag-SNPs, which are representative of 50 candidate genes, were genotyped by a custom GoldenGate Genotyping Assay. A two-step association analysis was performed without assuming ana priorigenetic model: step (1) a machine learning technique [gradient boosting machine (GBM)] was used to select the 15 SNPs with the highest variable importance measure; step (2) the GBM-selected SNPs were jointly tested in a linear regression model with natural log-transformed FeNO as the normally distributed outcome and with age, sex, and the SNPs as covariates. We replicated our results within an independent sample of 296 patients from the European Community Respiratory Health Survey III. We found that SNP rs987314 in family with sequence similarity 13 member A (FAM13A) and SNP rs3218258 in interleukin 2 receptor subunit beta (IL2RB) gene regions are significantly associated with FeNO in adult subjects with asthma. These genes are involved in different mechanisms that affect smooth muscle constriction and endothelial barrier function responses (FAM13A), or in immune response processes (IL2RB). Our findings contribute to the current knowledge on FeNO in asthma by identifying two novel SNPs associated with this biomarker of airways inflammation.

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来源期刊
Journal of breath research
Journal of breath research BIOCHEMICAL RESEARCH METHODS-RESPIRATORY SYSTEM
CiteScore
7.60
自引率
21.10%
发文量
49
审稿时长
>12 weeks
期刊介绍: Journal of Breath Research is dedicated to all aspects of scientific breath research. The traditional focus is on analysis of volatile compounds and aerosols in exhaled breath for the investigation of exogenous exposures, metabolism, toxicology, health status and the diagnosis of disease and breath odours. The journal also welcomes other breath-related topics. Typical areas of interest include: Big laboratory instrumentation: describing new state-of-the-art analytical instrumentation capable of performing high-resolution discovery and targeted breath research; exploiting complex technologies drawn from other areas of biochemistry and genetics for breath research. Engineering solutions: developing new breath sampling technologies for condensate and aerosols, for chemical and optical sensors, for extraction and sample preparation methods, for automation and standardization, and for multiplex analyses to preserve the breath matrix and facilitating analytical throughput. Measure exhaled constituents (e.g. CO2, acetone, isoprene) as markers of human presence or mitigate such contaminants in enclosed environments. Human and animal in vivo studies: decoding the ''breath exposome'', implementing exposure and intervention studies, performing cross-sectional and case-control research, assaying immune and inflammatory response, and testing mammalian host response to infections and exogenous exposures to develop information directly applicable to systems biology. Studying inhalation toxicology; inhaled breath as a source of internal dose; resultant blood, breath and urinary biomarkers linked to inhalation pathway. Cellular and molecular level in vitro studies. Clinical, pharmacological and forensic applications. Mathematical, statistical and graphical data interpretation.
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