Association between interleukin‐1 receptor antagonist gene and asthma‐related traits in a German adult population

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Abstract
A recent study in German and Italian families associated variants in the interleukin-1 receptor antagonist (IL1RA) gene with asthma. The aim of the present study was to further investigate the role of single nucleotide polymorphisms (SNPs) in the IL1RA gene in the development of atopy and lifelong asthma in a population-based study. DNA samples from the German centres of the European Community Respiratory Health Survey were analysed for genetic variants in the IL1RA gene and the development of asthma, atopy and bronchial hyperreactivity. Carriers of the rare G allele of SNP rs447713 had a significantly increased risk of developing asthma (P = 0.0013) and allergic sensitization (P = 0.0119). Carriers of the rare C allele of SNP rs3087271 had an increased risk of asthma (P = 0.0227) and high immunoglobulin E (IgE) levels (P = 0.0232). A haplotype built from eight SNPs in the IL1RA gene (A-C-A-G-A-C-G-A) was associated with a higher prevalence of asthma (P = 0.007) and high total IgE (P = 0.02). Bronchial hyperreactivity was positively associated with the haplotype A-C-G-G-A-C-G-C (P = 0.02) and negatively with the A-C-G-G-A-C-T-C (P = 0.03). A previously described association between IL1RA and asthma in families could be reproduced in a population-based sample. The genetic variants of IL1RA gene do not to seem to affect asthma alone, but to act as modulators of asthma-related traits as well, where different haplotypes drive the development of different phenotypes.