Polymorphisms in the IRF‐4 gene, asthma and recurrent bronchitis in children. Issue 10 (16th September 2013)

• Record Type: Journal Article
• Authors: Pinto, L. A.; Michel, S.; Klopp, N.; Vogelberg, C.; von, A.; Bufe, A.; Heinzmann, A.; Laub, O.; Simma, B.; Frischer, T.; Genuneit, J.; Gorski, M.; Illig, T.; Kabesch, M.
• Is Part Of: Clinical & experimental allergy. Volume 43:Issue 10(2013:Oct.)
• Page Start: 1152
• Page End: 1159
• Publication Date: 2013-09-16
• Subjects: Allergy -- Periodicals; Immunology -- Periodicals; 616.97
• DOI: 10.1111/cea.12175
• Languages: English
• ISSNs: 0954-7894

Abstract

<abstract abstract-type="main" id="cea12175-abs-0001"> <title>Summary</title> <sec id="cea12175-sec-0001" sec-type="section"> <title>Background</title> <p>Interferon‐regulatory factors (IRFs) play a crucial role in immunity, not only influencing interferon expression but also T cell differentiation. IRF‐4 was only recently recognized as a further major player in T cell differentiation.</p> </sec> <sec id="cea12175-sec-0002" sec-type="section"> <title>Objective</title> <p>As <italic>IRF‐1</italic> polymorphisms were shown to be associated with atopy and allergy, we comprehensively investigated effects of <italic>IRF‐4</italic> variants on allergy, asthma and related phenotypes in German children.</p> </sec> <sec id="cea12175-sec-0003" sec-type="section"> <title>Methods</title> <p>Fifteen tagging single nucleotide polymorphisms (SNPs) in the <italic>IRF‐4</italic> gene were genotyped by MALDI‐TOF MS in the cross‐sectional ISAAC phase II study population from Munich and Dresden (age 9–11; <italic>N </italic>=<italic> </italic>3099). Replication was performed in our previously established genome‐wide association study (GWAS) data set (<italic>N </italic>=<italic> </italic>1303) consisting of asthma cases from the Multicenter Asthma Genetic in Childhood (MAGIC) study and reference children from the ISAAC II study.</p> </sec> <sec id="cea12175-sec-0004" sec-type="section"> <title>Results</title> <p>SNPs were not significantly associated with asthma but with bronchial hyperresponsiveness, atopy and, most interestingly, with recurrent bronchitis in the first data set. The <italic>IRF‐4</italic> variant rs9378805 was associated with recurrent bronchitis in the ISAAC population and replicated in the GWAS data set where further SNPs showed associations with recurrent bronchitis and asthma.</p> </sec> <sec id="cea12175-sec-0005" sec-type="section"> <title>Conclusions</title> <p>We found genetic associations in <italic>IRF‐4</italic> to be associated with recurrent bronchitis in our two study populations. Associated polymorphisms are localized in a putative regulatory element in the 3′UTR region of <italic>IRF‐4</italic>. These findings suggest a putative role of <italic>IRF‐4</italic> in the development of bronchitis.</p> </sec> </abstract>