A thymic stromal lymphopoietin gene variant is associated with asthma and airway hyperresponsiveness.

TitleA thymic stromal lymphopoietin gene variant is associated with asthma and airway hyperresponsiveness.
Publication TypeJournal Article
Year of Publication2009
AuthorsHe, J-Q, Hallstrand, TS, Knight, D, Chan-Yeung, M, Sandford, A, Tripp, B, Zamar, D, Bossé, Y, Kozyrskyj, AL, James, A, Laprise, C, Daley, D
JournalJ Allergy Clin Immunol
Volume124
Issue2
Pagination222-9
Date Published2009 Aug
ISSN1097-6825
KeywordsAlleles, Asthma, Bronchial Hyperreactivity, Cytokines, Female, Gene Expression, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Linkage Disequilibrium, Male, Polymorphism, Single Nucleotide, Sex Factors
Abstract

BACKGROUND: The epithelial cell-derived protein thymic stromal lymphopoietin stimulates dendritic and mast cells to promote proallergic T(H)2 responses. Studies of transgenic expression of thymic stromal lymphopoietin and its receptor knockout mice have emphasized its critical role in the development of allergic inflammation. Association of genetic variation in thymic stromal lymphopoietin with IgE levels has been reported for human subjects.OBJECTIVE: The aim of this study was to evaluate the relationship between variants of thymic stromal lymphopoietin and asthma and related phenotypes.METHODS: We selected 6 single nucleotide polymorphisms in thymic stromal lymphopoietin and genotyped 5565 individuals from 4 independent asthma studies and tested for association with asthma, atopy, atopic asthma, and airway hyperresponsiveness by using a general allelic likelihood ratio test. P values were corrected for the effective number of independent single nucleotide polymorphisms and phenotypes.RESULTS: The A allele of rs1837253, which is 5.7 kb upstream of the transcription start site of the gene, was associated with protection from asthma, atopic asthma, and airway hyperresponsiveness, with the odds ratios and corrected P values for each being 0.79 and 0.0058; 0.75 and 0.0074; and 0.76 and 0.0094, respectively. Associations between thymic stromal lymphopoietin and asthma-related phenotypes were the most statistically significant observations in our study, which has to date examined 98 candidate genes. Full results are available online at http://genapha.icapture.ubc.ca/.CONCLUSIONS: A genetic variant in the region of the thymic stromal lymphopoietin gene is associated with the phenotypes of asthma and airway hyperresponsiveness.

DOI10.1016/j.jaci.2009.04.018
Alternate JournalJ. Allergy Clin. Immunol.
PubMed ID19539984