A functional IFN-λ4-generating DNA polymorphism could protect older asthmatic women from aeroallergen sensitization and associate with clinical features of asthma

Chinnaswamy, Sreedhar; Wardzynska, Aleksandra; Pawelczyk, Malgorzata; Makowska, Joanna; Skaaby, Tea; Mercader Bigas, Josep Maria; Ahluwalia, Tarunveer Singh; Grarup, Niels; Guindo Martínez, Marta; Bisgaard, Hans; Torrents, David; Linneberg, Allan; Bønnelykke, Klaus; Kowalski, Marek L.

A functional IFN-λ4-generating DNA polymorphism could protect older asthmatic women from aeroallergen sensitization and associate with clinical features of asthma

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dc.contributor.author Chinnaswamy, Sreedharca
dc.contributor.author Wardzynska, Aleksandraca
dc.contributor.author Pawelczyk, Malgorzataca
dc.contributor.author Makowska, Joannaca
dc.contributor.author Skaaby, Teaca
dc.contributor.author Mercader Bigas, Josep Mariaca
dc.contributor.author Ahluwalia, Tarunveer Singhca
dc.contributor.author Grarup, Nielsca
dc.contributor.author Guindo Martínez, Martaca
dc.contributor.author Bisgaard, Hansca
dc.contributor.author Torrents, Davidca
dc.contributor.author Linneberg, Allanca
dc.contributor.author Bønnelykke, Klausca
dc.contributor.author Kowalski, Marek L.ca
dc.date.accessioned 2018-07-17T07:38:11Z
dc.date.available 2018-07-17T07:38:11Z
dc.date.issued 2017
dc.description.abstract Lambda interferons (IFNLs) have immunomodulatory functions at epithelial barrier surfaces. IFN-λ4, a recent member of this family is expressed only in a subset of the population due to a frameshift-causing DNA polymorphism rs368234815. We examined the association of this polymorphism with atopy (aeroallergen sensitization) and asthma in a Polish hospital-based case-control cohort comprising of well-characterized adult asthmatics (n = 326) and healthy controls (n = 111). In the combined cohort, we saw no association of the polymorphism with asthma and/or atopy. However, the IFN-λ4-generating ΔG allele protected older asthmatic women (>50 yr of age) from atopic sensitization. Further, ΔG allele significantly associated with features of less-severe asthma including bronchodilator response and corticosteroid usage in older women in this Polish cohort. We tested the association of related IFNL locus polymorphisms (rs12979860 and rs8099917) with atopy, allergic rhinitis and presence/absence of asthma in three population-based cohorts from Europe, but saw no significant association of the polymorphisms with any of the phenotypes in older women. The polymorphisms associated marginally with lower occurrence of asthma in men/older men after meta-analysis of data from all cohorts. Functional and well-designed replication studies may reveal the true positive nature of these results.
dc.description.sponsorship SC was supported as a visiting scientist by Healthy Ageing Research Centre, Medical University of Lodz. This study was supported by Polish National Science Centre grant no. 2013/09/B/NZ6/00746 . The authors (SC, AW, MP, JM and MLK) have been partially supported by The Healthy Ageing Research Centre Project (REGPOT-2012-2013-1, 7FP). Inter99 and Health2006 study: TS was supported by a grant from the Lundbeck Foundation (Grant number R165-2013-15410), the Harboe Foundation (Grant number 16152), the A.P. Møller Foundation for the Advancement of Medical Science (Grant number 15-363), Aase and Einar Danielsen's Foundation (Grant number 10-001490), and the Weimann's grant. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk). GERA study: This work has been sponsored by the grant SEV-2011-00067 of Severo Ochoa Program, awarded by the Spanish Government. This work was supported by an EFSD/Lilly research fellowship. Josep M. Mercader was supported by Sara Borrell Fellowship from the Instituto Carlos III. Sílvia Bonàs was FI-DGR Fellowship from FI-DGR 2013 from Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR, Generalitat de Catalunya). COPSAC2000 study: We greatly acknowledge the private and public research funding allocated to COPSAC and listed on www.copsac.com, with special thanks to The Lundbeck Foundation (Grant nr. R16-A1694); Ministry of Health (Grant nr. 903516); Danish Council for Strategic Research (Grant nr.: 0603-00280B); The Danish Council for Independent Research and The Capital Region Research Foundation as core supporters.
dc.format.mimetype application/pdf
dc.identifier.citation Chinnaswamy S, Wardzynska A, Pawelczyk M, Makowska J, Skaaby T, Mercader JM et al. A functional IFN-lambda4-generating DNA polymorphism could protect older asthmatic women from aeroallergen sensitization and associate with clinical features of asthma. Sci Rep. 2017 Sep 5;7(1):10500. DOI: 10.1038/s41598-017-10467-y
dc.identifier.doi http://dx.doi.org/10.1038/s41598-017-10467-y
dc.identifier.issn 2045-2322
dc.identifier.uri http://hdl.handle.net/10230/35174
dc.language.iso eng
dc.publisher Nature Publishing Groupca
dc.relation.ispartof Sci Rep. 2017 Sep 5;7(1):10500
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/316300
dc.rights © The Author(s) 2017. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword Genetic association study
dc.subject.keyword Viral infection
dc.title A functional IFN-λ4-generating DNA polymorphism could protect older asthmatic women from aeroallergen sensitization and associate with clinical features of asthmaca
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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