Simone Accordini, Valentina Lando, Lucia Calciano, Cristina Bombieri, Giovanni Malerba, Antonino Margagliotti, Cosetta Minelli, James Potts, Diana A van der Plaat, Mario Olivieri
{"title":"在患有哮喘的成年受试者中，FAM13AA和IL2RB基因中的SNPs与FeNO相关。","authors":"Simone Accordini, Valentina Lando, Lucia Calciano, Cristina Bombieri, Giovanni Malerba, Antonino Margagliotti, Cosetta Minelli, James Potts, Diana A van der Plaat, Mario Olivieri","doi":"10.1088/1752-7163/acfbf1","DOIUrl":null,"url":null,"abstract":"<p><p>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 an<i>a priori</i>genetic 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 (<i>FAM13A</i>) and SNP rs3218258 in interleukin 2 receptor subunit beta (<i>IL2RB</i>) 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 (<i>FAM13A</i>), or in immune response processes (<i>IL2RB</i>). Our findings contribute to the current knowledge on FeNO in asthma by identifying two novel SNPs associated with this biomarker of airways inflammation.</p>","PeriodicalId":15306,"journal":{"name":"Journal of breath research","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"SNPs in<i>FAM13A</i>and<i>IL2RB</i>genes are associated with FeNO in adult subjects with asthma.\",\"authors\":\"Simone Accordini, Valentina Lando, Lucia Calciano, Cristina Bombieri, Giovanni Malerba, Antonino Margagliotti, Cosetta Minelli, James Potts, Diana A van der Plaat, Mario Olivieri\",\"doi\":\"10.1088/1752-7163/acfbf1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 an<i>a priori</i>genetic 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 (<i>FAM13A</i>) and SNP rs3218258 in interleukin 2 receptor subunit beta (<i>IL2RB</i>) 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 (<i>FAM13A</i>), or in immune response processes (<i>IL2RB</i>). Our findings contribute to the current knowledge on FeNO in asthma by identifying two novel SNPs associated with this biomarker of airways inflammation.</p>\",\"PeriodicalId\":15306,\"journal\":{\"name\":\"Journal of breath research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2023-10-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of breath research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1088/1752-7163/acfbf1\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of breath research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1088/1752-7163/acfbf1","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
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.
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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