Positionally cloned genes and age-specific effects in asthma and atopy: an international population-based cohort study (ECRHS)
Identifieur interne : 001417 ( Istex/Curation ); précédent : 001416; suivant : 001418Positionally cloned genes and age-specific effects in asthma and atopy: an international population-based cohort study (ECRHS)
Auteurs : F. Castro-Giner [Espagne] ; R. De Cid [Espagne] ; J R Gonzalez [Espagne] ; D. Jarvis [Royaume-Uni] ; J. Heinrich [Allemagne] ; C. Janson [Suède] ; E R Omenaas [Norvège] ; M C Matheson [Australie] ; I. Pin [France] ; J M Ant [Espagne] ; M. Wjst [Allemagne] ; X. Estivill [Espagne] ; M. Kogevinas [Espagne, Grèce, Canada]Source :
- Thorax [ 0040-6376 ] ; 2010-02.
Descripteurs français
- Wicri :
- topic : Allergie.
English descriptors
- KwdEn :
- Allergy, Asthma, Asthma susceptibility gene, Atopic, Atopic asthma, Atopy, Barcelona, Body mass index, Bonferroni, Bonferroni correction, Candidate genes, Chromosome, Clin, Cohort, Comparison group, Ecrhs, European community, Gene, Genet, Gure, Haplotype, Health survey, High serum, Locus, Npsr1, Npsr1 gene, Npsr1 polymorphisms, Npsr1 snps, Odds ratios, Online, Online supplement, Onset asthma, Other studies, Persistent asthma, Phenotype, Polymorphism, Positional, Receptor, Respir, Respir crit care, Single nucleotide polymorphisms, Smoking status, Snp, Susceptibility, Thorax.
- Teeft :
- Allergy, Asthma, Asthma susceptibility gene, Atopic, Atopic asthma, Atopy, Barcelona, Body mass index, Bonferroni, Bonferroni correction, Candidate genes, Chromosome, Clin, Cohort, Comparison group, Ecrhs, European community, Gene, Genet, Gure, Haplotype, Health survey, High serum, Locus, Npsr1, Npsr1 gene, Npsr1 polymorphisms, Npsr1 snps, Odds ratios, Online, Online supplement, Onset asthma, Other studies, Persistent asthma, Phenotype, Polymorphism, Positional, Receptor, Respir, Respir crit care, Single nucleotide polymorphisms, Smoking status, Snp, Susceptibility, Thorax.
Abstract
Background Several genes identified by positional cloning have been associated with asthma and atopy, but few findings have been replicated. Age at onset of asthma has been associated with different phenotypic characteristics, and with variants at chromosome 17q21 identified through genome-wide association. This study examined the associations and age-specific effects on asthma, atopy and bronchial hyper-responsiveness (BHR) of five candidate genes previously identified by positional cloning (ADAM33, PHF11, NPSR1, DPP10, SPINK5). Methods 51 polymorphisms from 2474 participants from 13 countries who took part in the European Community Respiratory Health Survey (1990–2000) were studied. Asthma and age at onset of asthma were assessed by questionnaire data, BHR by methacholine challenge and atopy by specific immunoglobulin E to four common allergens. Results Significant associations with asthma, atopy and particularly for asthma with atopy were observed for a large region of 47 kb in the NPSR1 gene, even after Bonferroni correction for multiple comparisons (p<0.001). The associations with NPSR1 were stronger in those reporting a first attack of asthma before the age of 15, with statistically significant interactions with age of onset found for three SNPs. The evidence for ADAM33 and BHR and for an age-specific effect of two SNPs in DPP10 and asthma was weaker. Conclusion This study provides further evidence for an effect of NPSR1 on asthma, atopy and atopic asthma. In addition, this analysis suggests a role for NPSR1 in early-onset asthma driven by the strong effect of this gene on atopic asthma.
Url:
DOI: 10.1136/thx.2009.119628
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Castro-Giner</name><affiliation wicri:level="1"><mods:affiliation>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Centre for Research in Environmental Epidemiology (CREAL), Barcelona</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="De Cid, R" sort="De Cid, R" uniqKey="De Cid R" first="R" last="De Cid">R. De Cid</name><affiliation wicri:level="1"><mods:affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Genes and Disease Program, Center for Genomic Regulation, Barcelona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Genes and Disease Program, Center for Genomic Regulation, Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Gonzalez, J R" sort="Gonzalez, J R" uniqKey="Gonzalez J" first="J R" last="Gonzalez">J R Gonzalez</name><affiliation wicri:level="1"><mods:affiliation>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Centre for Research in Environmental Epidemiology (CREAL), Barcelona</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Jarvis, D" sort="Jarvis, D" uniqKey="Jarvis D" first="D" last="Jarvis">D. Jarvis</name><affiliation wicri:level="1"><mods:affiliation>Respiratory Epidemiology and Public Health Group, National Heart and Lung Institute, Imperial College, London, UK</mods:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Respiratory Epidemiology and Public Health Group, National Heart and Lung Institute, Imperial College, London</wicri:regionArea></affiliation></author><author><name sortKey="Heinrich, J" sort="Heinrich, J" uniqKey="Heinrich J" first="J" last="Heinrich">J. Heinrich</name><affiliation wicri:level="1"><mods:affiliation>Institute of Epidemiology, Helmholtz Zentrum München, Munich, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Epidemiology, Helmholtz Zentrum München, Munich</wicri:regionArea></affiliation></author><author><name sortKey="Janson, C" sort="Janson, C" uniqKey="Janson C" first="C" last="Janson">C. Janson</name><affiliation wicri:level="1"><mods:affiliation>Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden</mods:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medical Sciences, Respiratory Medicine and Allergology, Uppsala University, Uppsala</wicri:regionArea></affiliation></author><author><name sortKey="Omenaas, E R" sort="Omenaas, E R" uniqKey="Omenaas E" first="E R" last="Omenaas">E R Omenaas</name><affiliation wicri:level="1"><mods:affiliation>Institute of Medicine, University of Bergen, Haukeland University Hospital, Bergen, Norway</mods:affiliation><country xml:lang="fr">Norvège</country><wicri:regionArea>Institute of Medicine, University of Bergen, Haukeland University Hospital, Bergen</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway</mods:affiliation><country xml:lang="fr">Norvège</country><wicri:regionArea>Centre for Clinical Research, Haukeland University Hospital, Bergen</wicri:regionArea></affiliation></author><author><name sortKey="Matheson, M C" sort="Matheson, M C" uniqKey="Matheson M" first="M C" last="Matheson">M C Matheson</name><affiliation wicri:level="1"><mods:affiliation>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Victoria, Australia</mods:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Victoria</wicri:regionArea></affiliation></author><author><name sortKey="Pin, I" sort="Pin, I" uniqKey="Pin I" first="I" last="Pin">I. Pin</name><affiliation wicri:level="1"><mods:affiliation>Inserm, U823, Centre de Recherche Albert Bonniot, Immunobiologie et Immunothérapie des cancers, La Tronche, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm, U823, Centre de Recherche Albert Bonniot, Immunobiologie et Immunothérapie des cancers, La Tronche</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>University Joseph Fourier, Grenoble, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>University Joseph Fourier, Grenoble</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Centre Hospitalier Universitaire de Grenoble, Grenoble, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre Hospitalier Universitaire de Grenoble, Grenoble</wicri:regionArea></affiliation></author><author><name sortKey="Ant, J M" sort="Ant, J M" uniqKey="Ant J" first="J M" last="Ant">J M Ant</name><affiliation wicri:level="1"><mods:affiliation>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Centre for Research in Environmental Epidemiology (CREAL), Barcelona</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Department of Health and Experimental Sciences, University Pompeu Fabra, Barcelona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Health and Experimental Sciences, University Pompeu Fabra, Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Wjst, M" sort="Wjst, M" uniqKey="Wjst M" first="M" last="Wjst">M. Wjst</name><affiliation wicri:level="1"><mods:affiliation>German Research Center for Environmental Health, Helmholtz Centre GSF, Munich, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>German Research Center for Environmental Health, Helmholtz Centre GSF, Munich</wicri:regionArea></affiliation></author><author><name sortKey="Estivill, X" sort="Estivill, X" uniqKey="Estivill X" first="X" last="Estivill">X. Estivill</name><affiliation wicri:level="1"><mods:affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Genes and Disease Program, Center for Genomic Regulation, Barcelona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Genes and Disease Program, Center for Genomic Regulation, Barcelona</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Department of Health and Experimental Sciences, University Pompeu Fabra, Barcelona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Department of Health and Experimental Sciences, University Pompeu Fabra, Barcelona</wicri:regionArea></affiliation></author><author><name sortKey="Kogevinas, M" sort="Kogevinas, M" uniqKey="Kogevinas M" first="M" last="Kogevinas">M. Kogevinas</name><affiliation wicri:level="1"><mods:affiliation>Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Centre for Research in Environmental Epidemiology (CREAL), Barcelona</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain</mods:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>National School of Public Health, Athens, Greece</mods:affiliation><country xml:lang="fr">Grèce</country><wicri:regionArea>National School of Public Health, Athens</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>E-mail: kogevinas@creal.cat</mods:affiliation><country wicri:rule="url">Canada</country></affiliation></author></analytic><monogr></monogr><series><title level="j">Thorax</title><title level="j" type="abbrev">Thorax</title><idno type="ISSN">0040-6376</idno><idno type="eISSN">1468-3296</idno><imprint><publisher>BMJ Publishing Group Ltd and British Thoracic Society</publisher><date type="published" when="2010-02">2010-02</date><biblScope unit="volume">65</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="124">124</biblScope></imprint><idno type="ISSN">0040-6376</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0040-6376</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Allergy</term><term>Asthma</term><term>Asthma susceptibility gene</term><term>Atopic</term><term>Atopic asthma</term><term>Atopy</term><term>Barcelona</term><term>Body mass index</term><term>Bonferroni</term><term>Bonferroni correction</term><term>Candidate genes</term><term>Chromosome</term><term>Clin</term><term>Cohort</term><term>Comparison group</term><term>Ecrhs</term><term>European community</term><term>Gene</term><term>Genet</term><term>Gure</term><term>Haplotype</term><term>Health survey</term><term>High serum</term><term>Locus</term><term>Npsr1</term><term>Npsr1 gene</term><term>Npsr1 polymorphisms</term><term>Npsr1 snps</term><term>Odds ratios</term><term>Online</term><term>Online supplement</term><term>Onset asthma</term><term>Other studies</term><term>Persistent asthma</term><term>Phenotype</term><term>Polymorphism</term><term>Positional</term><term>Receptor</term><term>Respir</term><term>Respir crit care</term><term>Single nucleotide polymorphisms</term><term>Smoking status</term><term>Snp</term><term>Susceptibility</term><term>Thorax</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Allergy</term><term>Asthma</term><term>Asthma susceptibility gene</term><term>Atopic</term><term>Atopic asthma</term><term>Atopy</term><term>Barcelona</term><term>Body mass index</term><term>Bonferroni</term><term>Bonferroni correction</term><term>Candidate genes</term><term>Chromosome</term><term>Clin</term><term>Cohort</term><term>Comparison group</term><term>Ecrhs</term><term>European community</term><term>Gene</term><term>Genet</term><term>Gure</term><term>Haplotype</term><term>Health survey</term><term>High serum</term><term>Locus</term><term>Npsr1</term><term>Npsr1 gene</term><term>Npsr1 polymorphisms</term><term>Npsr1 snps</term><term>Odds ratios</term><term>Online</term><term>Online supplement</term><term>Onset asthma</term><term>Other studies</term><term>Persistent asthma</term><term>Phenotype</term><term>Polymorphism</term><term>Positional</term><term>Receptor</term><term>Respir</term><term>Respir crit care</term><term>Single nucleotide polymorphisms</term><term>Smoking status</term><term>Snp</term><term>Susceptibility</term><term>Thorax</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Allergie</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Background Several genes identified by positional cloning have been associated with asthma and atopy, but few findings have been replicated. Age at onset of asthma has been associated with different phenotypic characteristics, and with variants at chromosome 17q21 identified through genome-wide association. This study examined the associations and age-specific effects on asthma, atopy and bronchial hyper-responsiveness (BHR) of five candidate genes previously identified by positional cloning (ADAM33, PHF11, NPSR1, DPP10, SPINK5). Methods 51 polymorphisms from 2474 participants from 13 countries who took part in the European Community Respiratory Health Survey (1990–2000) were studied. Asthma and age at onset of asthma were assessed by questionnaire data, BHR by methacholine challenge and atopy by specific immunoglobulin E to four common allergens. Results Significant associations with asthma, atopy and particularly for asthma with atopy were observed for a large region of 47 kb in the NPSR1 gene, even after Bonferroni correction for multiple comparisons (p<0.001). The associations with NPSR1 were stronger in those reporting a first attack of asthma before the age of 15, with statistically significant interactions with age of onset found for three SNPs. The evidence for ADAM33 and BHR and for an age-specific effect of two SNPs in DPP10 and asthma was weaker. Conclusion This study provides further evidence for an effect of NPSR1 on asthma, atopy and atopic asthma. In addition, this analysis suggests a role for NPSR1 in early-onset asthma driven by the strong effect of this gene on atopic asthma.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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