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 (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. ; 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.