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Sci Rep. 2017 Sep 5;7(1):10500. doi: 10.1038/s41598-017-10467-y.

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

Author information

1
National Institute of Biomedical Genomics, PO:N.S.S, Kalyani, 741251, West Bengal, India. sc2@nibmg.ac.in.
2
Chair of Clinical Immunology and Microbiology, Healthy Aging Research Center, Medical University of Lodz, 251 Pomorska Str, 92-213, Lodz, Poland. sc2@nibmg.ac.in.
3
Dept. of Immunology, Rheumatology & Allergy, Medical University of Lodz, Lodz, 92-213, Poland.
4
Department of Rheumatology, Medical University of Lodz, 92-003, Lodz, Poland.
5
Research Centre for Prevention and Health, the Capital Region of Denmark, Copenhagen, Denmark.
6
Barcelona Supercomputing Center (BSC). Joint BSC-CRG-IRB Research Program in Computational Biology, 08034, Barcelona, Spain.
7
COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
8
The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark.
9
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
10
Department of Clinical Experimental Research, Rigshospitalet, Denmark.
11
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
12
Chair of Clinical Immunology and Microbiology, Healthy Aging Research Center, Medical University of Lodz, 251 Pomorska Str, 92-213, Lodz, Poland.

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.

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