IL4Rα mutations are associated with asthma exacerbations and mast cell/IgE expression

Sally E. Wenzel, Silvana Balzar, Elizabeth Ampleford, Gregory A. Hawkins, William W. Busse, William J. Calhoun, Mario Castro, K. Fan Chung, Serpil Erzurum, Benjamin Gaston, Elliot Israel, W. Gerald Teague, Douglas Curran-Everett, Deborah A. Meyers, Eugene R. Bleecker

Research output: Contribution to journalArticlepeer-review

105 Scopus citations


Background: Severe asthma has been associated with severe exacerbations, lower lung function and greater tissue inflammation. Previous studies have suggested that mutations in interleukin-4 receptor α (IL4Rα) are associated with lower lung function, higher IgE, and a gain in receptor function. However, an effect onexacerbations and tissue inflammation has not been shown. Hypothesis: Allelic substitutions in IL4Rα are associated with asthma exacerbations, lower lung function, and tissue inflammation, in particular to mast cells and IgE. Methods: Two well-characterized cohorts of subjects with severe asthma were analyzed for five single nucleotide polymorphisms (SNPs) in IL4Rα. These polymorphisms were compared with the history of severe asthma exacerbations and lung function. In the primary (National Jewish) cohort, these polymorphisms were also compared with endobronchial tissue inflammatory cells and local IgE. Results: In both cohorts, the presence of the minor alleles at E375A and Q551R, which were more common in African Americans, was associated with a history of severe exacerbations and lower lung function. In the National Jewish cohort, the C allele at E375A was associated with higher tissue mast cells and higher levels of IgE bound to mast cells. The significance for most of these associations remained when whites (the larger racial subgroup) were analyzed separately. Conclusions: SNPs in IL4Rα, which aremore common in African Americans, are associated with severe asthma exacerbations, lower lung function, and increased mast cell-related tissue inflammation. Further studies of the impact of these mutations in African Americans and on receptor function are indicated.

Original languageEnglish (US)
Pages (from-to)570-576
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number6
StatePublished - Mar 15 2007


  • Asthma
  • Exacerbations
  • Genetics
  • IL4Rα
  • IgE
  • Mast cells

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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