Polymorphisms in the interleukin-4 and interleukin-4 receptor alpha chain genes confer susceptibility to asthma and atopy in a Caucasian population

Clin Exp Allergy. 2003 Aug;33(8):1111-7. doi: 10.1046/j.1365-2222.2003.01731.x.


Background: IL-4 by binding to its receptor (IL-4R) is essential for the development of airway inflammation present in asthma, through the induction of IgE synthesis in B cells and differentiation of T cells to a Th2 phenotype.

Objective: To investigate the role of four common polymorphisms in the IL-4 (IL4-34CT and IL4-589CT) and IL-4Ralpha chain (IL4RAI50V and IL4RAQ576R) genes in conferring susceptibility to the development of atopy and/or asthma.

Methods: Two polymorphisms in the IL-4 gene promoter, IL4-34CT and IL4-589CT, and two polymorphisms in the IL-4Ralpha chain gene, IL4RAI50V and IL4RAQ576R, have been genotyped using PCR-based methods in 341 asthmatic families and in 184 non-asthmatic adults recruited from the south of England.

Results: Case-control analysis did not reveal differences in the distribution of the four polymorphisms between asthmatics and controls. However, the transmission disequilibrium test showed that the IL4-589 T allele was preferentially transmitted to asthmatic children (P=0.036) and that the IL4RAQ576 was preferentially transmitted to children with atopic asthma (P=0.018). Haplotype analysis showed a strong association between the IL4-34T/-589T haplotype and asthma per se (P=0.041), and a strong association between the IL4RA I50/Q576 haplotype and atopic asthma (P=0.006).

Conclusion: Our data suggest that polymorphisms in the IL-4 and IL-4Ralpha chain genes might play a role both conferring susceptibility to and modulating severity of atopy and asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Asthma / genetics
  • Asthma / immunology
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Genotype
  • Haplotypes
  • Humans
  • Hypersensitivity, Immediate / genetics*
  • Hypersensitivity, Immediate / immunology
  • Interleukin-4 / genetics*
  • Linkage Disequilibrium
  • Male
  • Phenotype
  • Polymorphism, Genetic*
  • Receptors, Interleukin-4 / genetics*
  • Statistics as Topic


  • Receptors, Interleukin-4
  • Interleukin-4