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Gene-gene interaction in asthma: IL4RA and IL13 in a Dutch population with asthma.

Authors: Howard, TD  Koppelman, GH  Xu, J  Zheng, SL  Postma, DS  Meyers, DA  Bleecker, ER 
Citation: Howard TD, etal., Am J Hum Genet. 2002 Jan;70(1):230-6. Epub 2001 Nov 14.
Pubmed: (View Article at PubMed) PMID:11709756
DOI: Full-text: DOI:10.1086/338242

Asthma is a common respiratory disease that is characterized by variable airways obstruction caused by acute and chronic bronchial inflammation; associated phenotypes include bronchial hyperresponsiveness (BHR), elevated total serum immunoglobulin E (IgE) levels, and skin tests positive to common allergens. Binding of interleukin-13 (IL13) or interleukin-4 (IL4) to the IL4 receptor (IL4R) induces the initial response for Th2 lymphocyte polarization. Both IL13 and IL4 are produced by Th2 cells and are capable of inducing isotype class-switching of B-cells to produce IgE after allergen exposure. These cytokines also share a common receptor component, IL4R alpha. We have investigated five IL4RA single-nucleotide polymorphisms in a population of Dutch families ascertained through a proband with asthma. By considering the probands and their spouses as an unrelated sample, we observed significant associations of atopy and asthma-related phenotypes with several IL4RA polymorphisms, including S478P and total serum IgE levels (P=.0007). A significant gene-gene interaction between S478P in IL4RA and the -1111 promoter variation in IL13, previously shown to be associated with BHR (P=.003), was detected. Individuals with the risk genotype for both genes were at almost five times greater risk for the development of asthma compared to individuals with both non-risk genotypes (P=.0004). These data suggest that variations in IL4RA contribute to elevated total serum IgE levels, and interaction between IL4RA and IL13 markedly increases an individual's susceptibility to asthma.

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CRRD Object Information
CRRD ID: 4890024
Created: 2010-12-14
Species: All species
Last Modified: 2010-12-14
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.