A Common variant in RAB27A gene is associated with fractional exhaled nitric oxide levels in adults (Articolo in rivista)

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  • A Common variant in RAB27A gene is associated with fractional exhaled nitric oxide levels in adults (Articolo in rivista) (literal)
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  • 2014-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1111/cea.12461 (literal)
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  • nology > Allergy & Clinical Immunology > Clinical & Experimental Allergy > Accepted Articles > Abstract JOURNAL TOOLS Get New Content Alerts Get RSS feed Save to My Profile Get Sample Copy Recommend to Your Librarian JOURNAL MENU Journal Home FIND ISSUES Current Issue All Issues Virtual Issues FIND ARTICLES Accepted Articles Most Accessed Editors' Choice GET ACCESS Subscribe / Renew FOR CONTRIBUTORS OnlineOpen Author Guidelines Submit an Article ABOUT THIS JOURNAL Society Information News Overview Editorial Board Permissions Advertise Contact SPECIAL FEATURES Wiley Job Network BSACI Guidelines Jobs Original Article-Basic Mechanisms in Allergic Disease You have full text access to this content A Common variant in RAB27A gene is associated with fractional exhaled nitric oxide levels in adults Emmanuelle Bouzigon1,2,*, Rachel Nadif3,4,+, Emma E. Thompson5,+, Maria Pina Concas6, Susan Kuldanek5, Gaixin Du5, Myriam Brossard1,2, Nolwenn Lavielle1,2, Chloé Sarnowski1,2, Amaury Vaysse1,2, Philippe Dessen7, Ralf JP van der Valk8,9,10, Liesbeth Duijts9,10,11, A John Henderson11, Vincent WV Jaddoe8,9,10, Johan C de Jongste9, GABRIEL consortium, EArly Genetics & Lifecourse Epidemiology (EAGLE) Consortium, Stefania Casula6, Ginevra Biino6,12, Marie-Hélène Dizier1,2, Isabelle Pin13,14,15, Régis Matran16,17, Mark Lathrop18, Mario Pirastu6,19, Florence Demenais1,2 andCarole Ober5 (2014)
    A Common variant in RAB27A gene is associated with fractional exhaled nitric oxide levels in adults
    in Clinical & experimental allergy (Online)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • nology > Allergy & Clinical Immunology > Clinical & Experimental Allergy > Accepted Articles > Abstract JOURNAL TOOLS Get New Content Alerts Get RSS feed Save to My Profile Get Sample Copy Recommend to Your Librarian JOURNAL MENU Journal Home FIND ISSUES Current Issue All Issues Virtual Issues FIND ARTICLES Accepted Articles Most Accessed Editors' Choice GET ACCESS Subscribe / Renew FOR CONTRIBUTORS OnlineOpen Author Guidelines Submit an Article ABOUT THIS JOURNAL Society Information News Overview Editorial Board Permissions Advertise Contact SPECIAL FEATURES Wiley Job Network BSACI Guidelines Jobs Original Article-Basic Mechanisms in Allergic Disease You have full text access to this content A Common variant in RAB27A gene is associated with fractional exhaled nitric oxide levels in adults Emmanuelle Bouzigon1,2,*, Rachel Nadif3,4,+, Emma E. Thompson5,+, Maria Pina Concas6, Susan Kuldanek5, Gaixin Du5, Myriam Brossard1,2, Nolwenn Lavielle1,2, Chloé Sarnowski1,2, Amaury Vaysse1,2, Philippe Dessen7, Ralf JP van der Valk8,9,10, Liesbeth Duijts9,10,11, A John Henderson11, Vincent WV Jaddoe8,9,10, Johan C de Jongste9, GABRIEL consortium, EArly Genetics & Lifecourse Epidemiology (EAGLE) Consortium, Stefania Casula6, Ginevra Biino6,12, Marie-Hélène Dizier1,2, Isabelle Pin13,14,15, Régis Matran16,17, Mark Lathrop18, Mario Pirastu6,19, Florence Demenais1,2 andCarole Ober5 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url
  • http://onlinelibrary.wiley.com/doi/10.1111/cea.12461/abstract;jsessionid=00B0CF46BD12EE6E86BC64F0FE64162F.f02t02 (literal)
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  • 1Inserm, UMR-946, Paris, France 2Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France 3Inserm, U1018, Centre for research in Epidemiology and Population Health (CESP), Respiratory and Environmental Epidemiology Team, Villejuif, France 4Univ Paris-Sud, UMRS 1018, Villejuif, France 5Department of Human Genetics, University of Chicago, Chicago, IL, USA 6Institute of Population Genetics, National Council of Research, Sassari, Italy 7Inserm, UMRS 985, Institut Gustave Roussy, Villejuif, France 8The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands 9Department of Pediatrics, Erasmus Medical Center, Rotterdam, The Netherlands 10Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands 11School of Social and Community Medicine, University of Bristol, UK 12Institute of Molecular Genetics, National Council of Research, Pavia, Italy 13INSERM, IAB, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, Grenoble, France 14Univ. Grenoble Alpes, IAB, Team of Environmental Epidemiology applied to Reproduction and Respiratory Health, Grenoble, France 15Pédiatrie, CHU de Grenoble, Grenoble, France 16Univ Lille Nord de France, Lille, France 17CHU, Lille, France 18McGill University and Génome Québec Innovation Centre, Montréal, Canada 19Ogliastra Genetic Park, Perdasdefogu, Sardinia, Italy (literal)
Titolo
  • A Common variant in RAB27A gene is associated with fractional exhaled nitric oxide levels in adults (literal)
Abstract
  • Background Exhaled nitric oxide (FeNO) is a biomarker for eosinophilic inflammation in the airways and for responsiveness to corticosteroids in asthmatics. Objective We sought to identify in adults the genetic determinants of fractional exhaled nitric oxide (FeNO) levels and to assess whether environmental and disease-related factors influence these associations. Methods We performed a genome-wide association study of FeNO through meta-analysis of two independent discovery samples of European ancestry: the outbred EGEA study (French Epidemiological study on the Genetics and Environment of Asthma, N=610 adults) and the Hutterites (N=601 adults), a founder population living on communal farms. Replication of main findings was assessed in adults from an isolated village in Sardinia (Talana study, N=450). We then investigated the influence of asthma, atopy and tobacco smoke exposure on these genetic associations and whether they were also associated with FeNO values in children of the EAGLE (EArly Genetics & Lifecourse Epidemiology, N=8,858) consortium. Results We detected a common variant in RAB27A (rs2444043) associated with FeNO that reached the genome-wide significant level (P=1.6x10-7) in the combined discovery and replication adult datasets. This SNP belongs to member of RAS oncogene family (RAB27A) and was associated with an expression quantitative trait locus for RAB27A in lymphoblastoid cell lines from asthmatics. A second suggestive locus (rs2194437, P=8.9x10-7) located nearby the sodium/calcium exchanger 1 (SLC8A1) was mainly detected in atopic subjects and influenced by inhaled corticosteroid use. These two loci were not associated with childhood FeNO values. Conclusions and Clinical Relevance This study identified a common variant located in RAB27A gene influencing FeNO levels specifically in adults and with a biological relevance to the regulation of FeNO levels. This study provides new insight into the biological mechanisms underlying FeNO levels in adults. (literal)
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