IL-4/IL-13 pathway genetics strongly influence serum IgE levels and childhood asthma

Autor: Michael Kabesch, Bernd Woitsch, Erika von Mutius, Christian Fritzsch, Stephan K. Weiland, David Carr, Michaela Schedel
Rok vydání: 2006
Předmět:
Zdroj: Journal of Allergy and Clinical Immunology. 117:269-274
ISSN: 0091-6749
DOI: 10.1016/j.jaci.2005.10.024
Popis: Background IgE production, a hallmark of asthma and atopic disease, may be under genetic control. Genes of the IL-4 and IL-13 pathway, central for IgE regulation, have so far only been assessed in studies of single gene effects. Objective Here we analyzed combined extended haplotypes involving IL-4 , IL-13 , their shared receptor chain IL-4Rα , and the intracellular signal transducer and activator of transcription, STAT6 , to assess the combined effect of single nucleotide polymorphisms in this important immunological signaling pathway. Methods We genotyped a large cross-sectional population of 1120 children age 9 to 11 years for 18 polymorphisms in the respective genes of the IL-4/IL-13 pathway. One polymorphism per gene was selected because of its putative functional role, and extended haplotypes were built in a stepwise procedure where gene-by-gene interactions were assessed by using a Cordell model. Results Combining polymorphisms in all 4 major pathway genes in a stepwise procedure, the risk for high serum IgE levels increased 10.8-fold ( P = .02) and the risk for the development of asthma increased by a factor of 16.8-fold ( P = .005) compared with the maximum effect of any single polymorphism. Significant interactions in a model with additive and dominant effects, for both pair and triplet combinations for asthma (lowest P = .005), and for pairs of polymorphisms in IgE regulation were observed (lowest P = .054). Conclusion These data indicate that only the combined analyses of genetic alterations in the IL-4/IL-13 pathway reveal its actual significance to the development of atopy and childhood asthma.
Databáze: OpenAIRE
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