A comprehensive analysis of interleukin-4 receptor polymorphisms and their association with atopy and IgE regulation in childhood

Background: The interleukin (IL) 4/IL13 pathway is involved in the
regulation of IgE production associated with atopic diseases.
Numerous polymorphisms have been identified in the coding region of
the IL4 receptor alpha chain (IL4Ra) and previous association
studies have shown conflicting results. Based on their putative
functional role, polymorphisms A148G, T1432C and A1652G, located in
the coding region of IL4Ra, were selected for association and
haplotype studies in a large German population sample (n = 1,120).
Methods: Genotyping was performed using allele-specific PCR and
restriction-enzyme-based assays. Haplotypes were estimated, and
population-derived IgE percentiles (50% IgE >60 IU/ml, 66% IgE
>115 IU/ml and 90% IgE >457 IU/ml) were calculated as outcome
variables in a haplotype trend regression analysis. Results: In our
population, only polymorphism T1432C showed a trend for a
protective effect against atopic rhinitis ( odds ratio, OR: 0.52,
95% confidence interval, CI: 0.26 - 1.02, p = 0.05). When
haplotypes were calculated, one haplotype was significantly
associated with elevated serum IgE levels at the 50th percentile (
OR 1.60, 95% CI 1.08 - 2.37, p = 0.02). Conclusions: These data
indicate that IL4Ra polymorphisms, although suggested to be
functionally relevant by in vitro studies, have only a minor
influence on IgE regulation in our large population sample.
Copyright (C) 2004 S. Karger AG, Basel.