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

Abstract

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.

• Authors: B Beghé, S Barton, S Rorke, Q Peng, I Sayers, T Gaunt, T P Keith, J B Clough, S T Holgate, J W Holloway
• Journal: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (Clin Exp Allergy) Vol. 33 Issue 8 Pg. 1111-7 (Aug 2003) ISSN: 0954-7894 [Print] England
• PMID: 12911786 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Interleukin-4
• Interleukin-4

Topics

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