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Multilocus haplotype analyses reveal association between 5 novel IL-15 polymorphisms and asthma
Thorsten Kurz1, Konstantin Strauch, Henriette Dietrich
1University Children's Hospital, University of Freiburg, Mathildenstrasse 1, 79106 Freiburg, Germany.
The Journal of Allergy and Clinical Immunology
|May 8, 2004
Summary
Interleukin-15 (IL-15) gene variants were analyzed for association with asthma and atopy. While individual polymorphisms showed no link, specific IL-15 haplotypes were significantly associated with asthma and atopy.
Area of Science:
- Immunology
- Genetics
- Allergy Research
Background:
- Interleukin-15 (IL-15) is a cytokine implicated in T-cell mediated inflammatory and autoimmune diseases.
- Upregulation of IL-15 is observed in various T-cell mediated inflammatory disorders.
- IL-15 may play a role in both T(H)1 and T(H)2 mediated inflammatory conditions.
Purpose of the Study:
- To identify single nucleotide polymorphisms (SNPs) within the IL-15 gene.
- To investigate the association of these IL-15 gene polymorphisms with inflammatory and atopic phenotypes, specifically asthma and atopy.
Main Methods:
- Screening for SNPs using single-strand conformation polymorphism (SSCP) analysis.
- Genotyping of identified polymorphisms via restriction fragment length polymorphism (RFLP).
- Association analysis using Armitage trend test and haplotype frequency estimation with FASTEHPLUS and FAMHAP programs.
Main Results:
- Five novel noncoding nucleotide sequence variants in the IL-15 gene were identified and genotyped.
- No significant association was found between individual IL-15 polymorphisms and the phenotypes of bronchial asthma or atopy.
- Multilocus haplotype analysis revealed a highly significant association between IL-15 haplotypes and asthma (P = 6.1 x 10(-5)) and a nominally significant association with atopy (P = 0.0232).
Conclusions:
- The findings reinforce the potential involvement of IL-15 in the pathogenesis of allergic diseases.
- Specific combinations of IL-15 gene variants (haplotypes) are strongly associated with asthma and atopy.
- Further research into the role of IL-15 in allergic inflammation is warranted.