Polymorphisms in the IRF-4 gene, asthma and recurrent bronchitis in children

Background: 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.

Objective: As IRF-1 polymorphisms were shown to be associated with atopy and allergy, we comprehensively investigated effects of IRF-4 variants on allergy, asthma and related phenotypes in German children.

Methods: Fifteen tagging single nucleotide polymorphisms (SNPs) in the IRF-4 gene were genotyped by MALDI-TOF MS in the cross-sectional ISAAC phase II study population from Munich and Dresden (age 9-11; N = 3099). Replication was performed in our previously established genome-wide association study (GWAS) data set (N = 1303) consisting of asthma cases from the Multicenter Asthma Genetic in Childhood (MAGIC) study and reference children from the ISAAC II study.

Results: SNPs were not significantly associated with asthma but with bronchial hyperresponsiveness, atopy and, most interestingly, with recurrent bronchitis in the first data set. The IRF-4 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.

Conclusions: We found genetic associations in IRF-4 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 IRF-4. These findings suggest a putative role of IRF-4 in the development of bronchitis.