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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

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

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.[1]

References

  1. Gene-gene interaction in asthma: IL4RA and IL13 in a Dutch population with asthma. Howard, T.D., Koppelman, G.H., Xu, J., Zheng, S.L., Postma, D.S., Meyers, D.A., Bleecker, E.R. Am. J. Hum. Genet. (2002) [Pubmed]
 
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