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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)

Nyckelord

Adolescent

Adult

Alleles

Allergens

pharmacology

CD4-Positive T-Lymphocytes

drug effects

enzymology

immunology

metabolism

Exons

genetics

immunology

Female

Gene Expression Profiling

Gene Frequency

genetics

immunology

Genetic Predisposition to Disease

Haplotypes

genetics

immunology

Humans

Introns

genetics

immunology

Male

Middle Aged

Oligonucleotide Array Sequence Analysis

Pollen

immunology

Polymorphism

Single Nucleotide

genetics

immunology

Protein-Tyrosine Kinases

drug effects

genetics

immunology

Receptors

Antigen

T-Cell

drug effects

immunology

Rhinitis

Allergic

Seasonal

genetics

immunology

Signal Transduction

genetics

immunology

Th2 Cells

drug effects

enzymology

immunology

metabolism

Young Adult

single nucleotide polymorphism

allergic rhinitis

pathway

allergic rhinitis; pathway; single nucleotide polymorphism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)