Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Allergy Clin Immunol. 2006 Feb;117(2):269-74.

IL-4/IL-13 pathway genetics strongly influence serum IgE levels and childhood asthma.

Author information

  • 1University Children's Hospital Munich, Germany. Michael.Kabesch@med.uni-muenchen.de

Abstract

BACKGROUND:

IgE production, a hallmark of asthma and atopic disease, may be under genetic control. Genes of the IL-4 and IL-13 pathway, central for IgE regulation, have so far only been assessed in studies of single gene effects.

OBJECTIVE:

Here we analyzed combined extended haplotypes involving IL-4, IL-13, their shared receptor chain IL-4Ralpha, and the intracellular signal transducer and activator of transcription, STAT6, to assess the combined effect of single nucleotide polymorphisms in this important immunological signaling pathway.

METHODS:

We genotyped a large cross-sectional population of 1120 children age 9 to 11 years for 18 polymorphisms in the respective genes of the IL-4/IL-13 pathway. One polymorphism per gene was selected because of its putative functional role, and extended haplotypes were built in a stepwise procedure where gene-by-gene interactions were assessed by using a Cordell model.

RESULTS:

Combining polymorphisms in all 4 major pathway genes in a stepwise procedure, the risk for high serum IgE levels increased 10.8-fold (P = .02) and the risk for the development of asthma increased by a factor of 16.8-fold (P = .005) compared with the maximum effect of any single polymorphism. Significant interactions in a model with additive and dominant effects, for both pair and triplet combinations for asthma (lowest P = .005), and for pairs of polymorphisms in IgE regulation were observed (lowest P = .054).

CONCLUSION:

These data indicate that only the combined analyses of genetic alterations in the IL-4/IL-13 pathway reveal its actual significance to the development of atopy and childhood asthma.

PMID:
16461126
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk