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A haplotype in the inducible T-cell tyrosine kinase is a risk factor for seasonal allergic rhinitis

Benson, M.; Mobini, R.; Barrenas, F.; Halldén, Christer LU ; Naluai, A. T.; Säll, Torbjörn LU and Cardell, L. O. (2009) In Allergy 64(9). p.1286-1291
Abstract
Background: Identification of disease-associated single nucleotide polymorphisms (SNPs) in seasonal allergic rhinitis (SAR) may be facilitated by focusing on genes in a disease-associated pathway. Objective: To search for SNPs in genes that belong to the T-cell receptor (TCR) pathway and that change in expression in allergen-challenged CD4+ cells from patients with SAR. Methods: CD4+ cells from patients with SAR were analysed with gene expression microarrays. Allele, genotype and haplotype frequencies were compared in 251 patients and 386 healthy controls. Results: Gene expression microarray analysis of allergen-challenged CD4+ cells from patients with SAR showed that 25 of 38 TCR pathway genes were differentially expressed. A total of 62... (More)
Background: Identification of disease-associated single nucleotide polymorphisms (SNPs) in seasonal allergic rhinitis (SAR) may be facilitated by focusing on genes in a disease-associated pathway. Objective: To search for SNPs in genes that belong to the T-cell receptor (TCR) pathway and that change in expression in allergen-challenged CD4+ cells from patients with SAR. Methods: CD4+ cells from patients with SAR were analysed with gene expression microarrays. Allele, genotype and haplotype frequencies were compared in 251 patients and 386 healthy controls. Results: Gene expression microarray analysis of allergen-challenged CD4+ cells from patients with SAR showed that 25 of 38 TCR pathway genes were differentially expressed. A total of 62 SNPs were analysed in eight of the 25 genes; ICOS, IL4, IL5, IL13, CSF2, CTLA4, the inducible T-cell tyrosine kinase (ITK) and CD3D. Significant chi-squared values were identified for several markers in the ITK kinase gene region. A total of five SNPs were nominally significant at the 5% level. Haplotype analysis of the five significant SNPs showed increased frequency of a haplotype that covered most of the coding part of ITK. The functional relevance of ITK was supported by analysis of an independent material, which showed increased expression of ITK in allergen-challenged CD4+ cells from patients, but not from controls. Conclusion: Analysis of SNPs in TCR pathway genes revealed that a haplotype that covers a major part of the coding sequence of ITK is a risk factor for SAR. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
single nucleotide polymorphism, allergic rhinitis, pathway
in
Allergy
volume
64
issue
9
pages
1286 - 1291
publisher
Wiley-Blackwell
external identifiers
  • wos:000268968700006
  • scopus:68949209328
ISSN
1398-9995
DOI
10.1111/j.1398-9995.2009.01991.x
language
English
LU publication?
yes
id
14a11436-ac70-465e-ae4e-46738f35cbbe (old id 1477477)
date added to LUP
2009-09-28 14:42:56
date last changed
2017-07-09 04:10:46
@article{14a11436-ac70-465e-ae4e-46738f35cbbe,
  abstract     = {Background: Identification of disease-associated single nucleotide polymorphisms (SNPs) in seasonal allergic rhinitis (SAR) may be facilitated by focusing on genes in a disease-associated pathway. Objective: To search for SNPs in genes that belong to the T-cell receptor (TCR) pathway and that change in expression in allergen-challenged CD4+ cells from patients with SAR. Methods: CD4+ cells from patients with SAR were analysed with gene expression microarrays. Allele, genotype and haplotype frequencies were compared in 251 patients and 386 healthy controls. Results: Gene expression microarray analysis of allergen-challenged CD4+ cells from patients with SAR showed that 25 of 38 TCR pathway genes were differentially expressed. A total of 62 SNPs were analysed in eight of the 25 genes; ICOS, IL4, IL5, IL13, CSF2, CTLA4, the inducible T-cell tyrosine kinase (ITK) and CD3D. Significant chi-squared values were identified for several markers in the ITK kinase gene region. A total of five SNPs were nominally significant at the 5% level. Haplotype analysis of the five significant SNPs showed increased frequency of a haplotype that covered most of the coding part of ITK. The functional relevance of ITK was supported by analysis of an independent material, which showed increased expression of ITK in allergen-challenged CD4+ cells from patients, but not from controls. Conclusion: Analysis of SNPs in TCR pathway genes revealed that a haplotype that covers a major part of the coding sequence of ITK is a risk factor for SAR.},
  author       = {Benson, M. and Mobini, R. and Barrenas, F. and Halldén, Christer and Naluai, A. T. and Säll, Torbjörn and Cardell, L. O.},
  issn         = {1398-9995},
  keyword      = {single nucleotide polymorphism,allergic rhinitis,pathway},
  language     = {eng},
  number       = {9},
  pages        = {1286--1291},
  publisher    = {Wiley-Blackwell},
  series       = {Allergy},
  title        = {A haplotype in the inducible T-cell tyrosine kinase is a risk factor for seasonal allergic rhinitis},
  url          = {http://dx.doi.org/10.1111/j.1398-9995.2009.01991.x},
  volume       = {64},
  year         = {2009},
}