Multilocus haplotype analyses reveal association between 5 novel IL-15 polymorphisms and asthma.
BACKGROUND
IL-15 is a T(H)1-related cytokine that is involved in the inflammatory response in various infectious and autoimmune diseases. IL-15 has recently been shown to be upregulated in T-cell-mediated inflammatory disorders. The observations suggest a potential role for this cytokine in a variety of pathologic conditions, including T(H)1-mediated and T(H)2-mediated inflammatory diseases.


OBJECTIVE
In this study, we searched for single nucleotide polymorphisms in the whole IL-15 gene and investigated their association with inflammatory and/or atopic phenotypes.


METHODS
The screening for single nucleotide polymorphisms was performed by single-strand conformation polymorphism analysis. Genotyping of the identified polymorphisms was performed by restriction fragment length polymorphism. Genotypic association analysis used the Armitage trend test. Haplotype frequency estimation and subsequent testing for differences between cases and controls were performed by using the programs FASTEHPLUS and FAMHAP.


RESULTS
We identified 5 novel noncoding nucleotide sequence variants, all of which were typed in our asthmatic, our atopic, and our control population. According to the Armitage trend test, none of the 5 polymorphisms is associated with the phenotype bronchial asthma or atopy. However, multilocus haplotype analysis based on simulations to find out whether the haplotype frequencies differed between cases and controls by using the program FAMHAP yielded a P value of 6.1 x 10(-5) in the asthmatic versus the control population, which is highly significant. Furthermore, we obtained a nominally significant result of P=.0232 for the atopic versus the control population by using FAMHAP.


CONCLUSIONS
These results strongly underscore previous findings that suggest a potential role of this cytokine in allergic diseases.
Kurz
Thorsten
T
University Children's Hospital, University of Freiburg, Mathildenstrasse 1, 79106 Freiburg, Germany.
Strauch
Konstantin
K
Dietrich
Henriette
H
Braun
Sandra
S
Hierl
Steffen
S
Jerkic
Silvija-Pera
SP
Wienker
Thomas F
TF
Deichmann
Klaus A
KA
Heinzmann
Andrea
A
D000293:Adolescent; D001249:Asthma / Q000235:genetics* / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics / Q000276:immunology; D019409:Interleukin-15 / Q000235:genetics*; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
D019409:Interleukin-15