Original Paper

A Common Exonic Variant of Interleukin21 Confers Susceptibility to Atopic Asthma
Rajshekhar Chatterjee, Jyotsna Batra, Balaram Ghosh

Molecular Immunogenetics Laboratory, Institute of Genomics and Integrative Biology, New Delhi, India

Address of Corresponding Author

Int Arch Allergy Immunol 2009;148:137-146 (DOI: 10.1159/000155744)

  Key Words

• Asthma
• Haplotype
• IL-21 level
• Microsatellite repeat marker
• Single nucleotide polymorphisms

  Abstract

Background: Interleukin (IL)-21, an IL-2 family multifunctional cytokine, is produced by activated CD4+ T cells and is known to potentially affect growth, survival and function of numerous immune cells. As IL-21 regulates IgE production, a key mediator of various allergic disorders and asthma, it is a prime candidate gene for studying atopic asthma. Methods: In atopic asthma, analyses of four single nucleotide polymorphisms (SNP; C1455T, G1472T, C5250T and C8381T), a tetranucleotide microsatellite repeat (GAAT)_n and their haplotypes were performed, and serum total IgE (TsIgE) was determined in ethnically matched unrelated patients (n = 255), unrelated controls (n = 245) and nuclear families (n = 140). Correlation between an exonic SNP C5250T in the asthmatics with serum IL-21 levels was also made. Results: In both the case-control and family study groups, the exon-3 polymorphism C5250T of the IL21 gene was significantly associated with atopic asthma and TsIgE. The C5250T polymorphism was found to affect the concentration of serum IL-21 levels in atopic asthmatics. Also, this observation was supported by the structural alteration in IL21 mRNA as predicted by mfold software. Further, our haplotypic studies indicated that while minor haplotypes 4_C_T_C_C and two locus haplotype T_C were associated with asthma in the case-control cohort, none of the major haplotypes was found to be associated with either asthma or TsIgE levels. Conclusion: Our study provides evidence that IL21 is associated with atopic asthma, TsIgE and serum IL-21 levels. Thus, it may initiate further research to elucidate the role of the IL21 gene in asthma pathogenesis.

Copyright © 2008 S. Karger AG, Basel

  Author Contacts

Correspondence to: Dr. Balaram Ghosh
Molecular Immunogenetics Laboratory
Institute of Genomics and Integrative Biology
Mall Road, Delhi-110007 (India)
Tel. +91 11 276 62580, Fax +91 11 276 67471, E-Mail bghosh@igib.res.in

  Article Information

Received: January 31, 2008
Accepted after revision: May 20, 2008
Published online: September 19, 2008
Number of Print Pages : 10
Number of Figures : 2, Number of Tables : 6, Number of References : 30