IL4R alpha mutations are associated with asthma exacerbations and mast cell/IgE expression

Am J Respir Crit Care Med. 2007 Mar 15;175(6):570-6. doi: 10.1164/rccm.200607-909OC. Epub 2006 Dec 14.


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 alpha (IL4Ralpha) are associated with lower lung function, higher IgE, and a gain in receptor function. However, an effect on exacerbations and tissue inflammation has not been shown.

Hypothesis: Allelic substitutions in IL4Ralpha 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 IL4Ralpha. 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 IL4Ralpha, which are more 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Asthma / genetics*
  • Black People / genetics
  • Cohort Studies
  • Female
  • Forced Expiratory Volume / genetics
  • Gene Frequency
  • Haplotypes
  • Humans
  • Immunoglobulin E / metabolism*
  • Inflammation / genetics
  • Inflammation / metabolism
  • Interleukin-4 Receptor alpha Subunit / genetics*
  • Male
  • Mast Cells / metabolism*
  • Mutation
  • Polymorphism, Single Nucleotide*
  • Severity of Illness Index
  • White People / genetics


  • IL4R protein, human
  • Interleukin-4 Receptor alpha Subunit
  • Immunoglobulin E