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A haplotype in the inducible T‐cell tyrosine kinase is a risk factor for seasonal allergic rhinitis
Author(s) -
Benson M.,
Mobini R.,
Barrenäs F.,
Halldén C.,
Naluai Å. T.,
Säll T.,
Cardell L. O.
Publication year - 2009
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/j.1398-9995.2009.01991.x
Subject(s) - single nucleotide polymorphism , haplotype , gene , biology , genotype , allele , immunology , t cell receptor , immunoglobulin e , genetics , candidate gene , coding region , microbiology and biotechnology , t cell , antibody , immune system
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.