Gene-gene interaction in asthma: Il4ra and il13 in a dutch population with asthma

Timothy D. Howard, Gerard H. Koppelman, anfeng Xu, Siqun L. Zheng, Dirkje S. Postma, Deborah A. Meyers, Eugene R. Bleecker

Research output: Contribution to journalArticlepeer-review

296 Scopus citations

Abstract

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, IL4Rα. 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 nonrisk 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.

Original languageEnglish (US)
Pages (from-to)230-236
Number of pages7
JournalAmerican Journal of Human Genetics
Volume70
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint

Dive into the research topics of 'Gene-gene interaction in asthma: Il4ra and il13 in a dutch population with asthma'. Together they form a unique fingerprint.

Cite this