A thymic stromal lymphopoietin gene variant is associated with asthma and airway hyperresponsiveness.
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.
He
Jian-Qing
JQ
James Hogg Imaging, Cell Analysis, and Phenotyping Toward Understanding Responsive, Reparative, Remodelling, and Recombinant Events (iCAPTURE) Centre, University of British Columbia, Vancouver, British Columbia, Canada.
Hallstrand
Teal S
TS
Knight
Darryl
D
Chan-Yeung
Moira
M
Sandford
Andrew
A
Tripp
Ben
B
Zamar
David
D
Bossé
Yohan
Y
Kozyrskyj
Anita L
AL
James
Alan
A
Laprise
Catherine
C
Daley
Denise
D
D000483:Alleles; D001249:Asthma / Q000235:genetics* / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity / Q000235:genetics*; D016207:Cytokines / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D000094632:Thymic Stromal Lymphopoietin