Cargando…
A functional IFN-λ4-generating DNA polymorphism could protect older asthmatic women from aeroallergen sensitization and associate with clinical features of asthma
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 (aer...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585370/ https://www.ncbi.nlm.nih.gov/pubmed/28874741 http://dx.doi.org/10.1038/s41598-017-10467-y |
_version_ | 1783261610163306496 |
---|---|
author | Chinnaswamy, Sreedhar Wardzynska, Aleksandra Pawelczyk, Malgorzata Makowska, Joanna Skaaby, Tea Mercader, Josep M. Ahluwalia, Tarunveer S. Grarup, Niels Guindo-Martinez, Marta Bisgaard, Hans Torrents, David Linneberg, Allan Bønnelykke, Klaus Kowalski, Marek L. |
author_facet | Chinnaswamy, Sreedhar Wardzynska, Aleksandra Pawelczyk, Malgorzata Makowska, Joanna Skaaby, Tea Mercader, Josep M. Ahluwalia, Tarunveer S. Grarup, Niels Guindo-Martinez, Marta Bisgaard, Hans Torrents, David Linneberg, Allan Bønnelykke, Klaus Kowalski, Marek L. |
author_sort | Chinnaswamy, Sreedhar |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5585370 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55853702017-09-06 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, Josep M. Ahluwalia, Tarunveer S. Grarup, Niels Guindo-Martinez, Marta Bisgaard, Hans Torrents, David Linneberg, Allan Bønnelykke, Klaus Kowalski, Marek L. Sci Rep Article 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. Nature Publishing Group UK 2017-09-05 /pmc/articles/PMC5585370/ /pubmed/28874741 http://dx.doi.org/10.1038/s41598-017-10467-y Text en © 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/. |
spellingShingle | Article Chinnaswamy, Sreedhar Wardzynska, Aleksandra Pawelczyk, Malgorzata Makowska, Joanna Skaaby, Tea Mercader, Josep M. Ahluwalia, Tarunveer S. Grarup, Niels Guindo-Martinez, 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 |
title | A functional IFN-λ4-generating DNA polymorphism could protect older asthmatic women from aeroallergen sensitization and associate with clinical features of asthma |
title_full | A functional IFN-λ4-generating DNA polymorphism could protect older asthmatic women from aeroallergen sensitization and associate with clinical features of asthma |
title_fullStr | A functional IFN-λ4-generating DNA polymorphism could protect older asthmatic women from aeroallergen sensitization and associate with clinical features of asthma |
title_full_unstemmed | A functional IFN-λ4-generating DNA polymorphism could protect older asthmatic women from aeroallergen sensitization and associate with clinical features of asthma |
title_short | A functional IFN-λ4-generating DNA polymorphism could protect older asthmatic women from aeroallergen sensitization and associate with clinical features of asthma |
title_sort | functional ifn-λ4-generating dna polymorphism could protect older asthmatic women from aeroallergen sensitization and associate with clinical features of asthma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585370/ https://www.ncbi.nlm.nih.gov/pubmed/28874741 http://dx.doi.org/10.1038/s41598-017-10467-y |
work_keys_str_mv | AT chinnaswamysreedhar afunctionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT wardzynskaaleksandra afunctionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT pawelczykmalgorzata afunctionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT makowskajoanna afunctionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT skaabytea afunctionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT mercaderjosepm afunctionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT ahluwaliatarunveers afunctionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT grarupniels afunctionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT guindomartinezmarta afunctionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT bisgaardhans afunctionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT torrentsdavid afunctionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT linnebergallan afunctionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT bønnelykkeklaus afunctionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT kowalskimarekl afunctionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT chinnaswamysreedhar functionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT wardzynskaaleksandra functionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT pawelczykmalgorzata functionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT makowskajoanna functionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT skaabytea functionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT mercaderjosepm functionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT ahluwaliatarunveers functionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT grarupniels functionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT guindomartinezmarta functionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT bisgaardhans functionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT torrentsdavid functionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT linnebergallan functionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT bønnelykkeklaus functionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma AT kowalskimarekl functionalifnl4generatingdnapolymorphismcouldprotectolderasthmaticwomenfromaeroallergensensitizationandassociatewithclinicalfeaturesofasthma |