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

作者：He Jian Qing; Hallstrand Teal S; Knight Darryl; Chan Yeung Moira; Sandford Andrew; Tripp Ben; Zamar David; Bosse Yohan; Kozyrskyj Anita L; James Alan; Laprise Catherine; Daley Denise^*

来源：Journal of Allergy and Clinical Immunology, 2009, 124(2): 222-229.

DOI：10.1016/j.jaci.2009.04.018

• Airway hyperresponsiveness
• association study
• asthma genetics
• atopy
• polymorphisms
• thymic stromal lymphopoietin

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. (J Allergy Clin Immunol 2009;124:222-9.)

• 出版日期2009-8