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

被引:96
作者
He, Jian-Qing [1 ]
Hallstrand, Teal S. [5 ]
Knight, Darryl [1 ,2 ]
Chan-Yeung, Moira [3 ]
Sandford, Andrew [1 ,4 ]
Tripp, Ben [1 ]
Zamar, David [1 ]
Bosse, Yohan [6 ,7 ]
Kozyrskyj, Anita L. [8 ,9 ]
James, Alan [9 ,10 ]
Laprise, Catherine [11 ,12 ]
Daley, Denise [1 ,4 ]
机构
[1] Univ British Columbia, UBC James Hogg iCAPTURE Ctr, Vancouver, BC V6Z 1Y6, Canada
[2] Univ British Columbia, Dept Anesthesiol Pharmacol & Therapeut, Vancouver, BC V5Z 1M9, Canada
[3] Univ British Columbia, Occupat & Environm Lung Dis Unit, Vancouver, BC V5Z 1M9, Canada
[4] Univ British Columbia, Div Resp Med, Dept Med, Vancouver, BC V5Z 1M9, Canada
[5] Univ British Columbia, Div Pulm & Crit Care, Dept Med, Vancouver, BC V5Z 1M9, Canada
[6] Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ, Canada
[7] Laval Univ Hosp Res Ctr, Laval, PQ, Canada
[8] Univ Alberta, Fac Med & Dent, Dept Pediat, Edmonton, AB, Canada
[9] Univ Manitoba, Fac Med, Dept Pediat & Child Hlth, Winnipeg, MB, Canada
[10] Sir Charles Gairdner Hosp, W Australian Sleep Disorders Res Inst, Perth, WA, Australia
[11] Univ Quebec Chicoutimi, Dept Sci Fondamentales, Chicoutimi, PQ, Canada
[12] Univ Montreal, Chicoutimi Hosp, Community Genom Med Ctr, Montreal, PQ H3C 3J7, Canada
基金
加拿大健康研究院; 英国医学研究理事会;
关键词
Airway hyperresponsiveness; association study; asthma genetics; atopy; polymorphisms; thymic stromal lymphopoietin; SINGLE-NUCLEOTIDE POLYMORPHISMS; PRIMARY PREVENTION; LUNG-FUNCTION; CHILDHOOD; RECEPTOR; TSLP; DISEQUILIBRIUM; DISEASE; RISK; INFLAMMATION;
D O I
10.1016/j.jaci.2009.04.018
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
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.)
引用
收藏
页码:222 / 229
页数:8
相关论文
共 56 条
[1]   Thymic stfomal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells [J].
Allakhverdi, Zoulfia ;
Comeau, Michael R. ;
Jessup, Heidi K. ;
Yoon, Bo-Rin Park ;
Brewer, Avery ;
Chartier, Suzanne ;
Paquette, Nicole ;
Ziegler, Steven F. ;
Sarfati, Marika ;
Delespesse, Guy .
JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (02) :253-258
[2]   Association of urokinase-type plasminogen activator with asthma and atopy [J].
Begin, Philippe ;
Tremblay, Karine ;
Daley, Denise ;
Lemire, Mathieu ;
Claveau, Sebastien ;
Salesse, Charleen ;
Kacel, Sabine ;
Montpetit, Alexandre ;
Becker, Allan ;
Chan-Yeung, Moira ;
Kozyrskyj, Anita L. ;
Hudson, Thomas J. ;
Laprise, Catherine .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2007, 175 (11) :1109-1116
[3]   Respiratory symptoms and lung function in aborigines from tropical western Australia [J].
Bremner, PR ;
de Klerk, NH ;
Ryan, GF ;
James, AL ;
Musk, M ;
Murray, C ;
Le Söuef, PN ;
Young, S ;
Spargo, R ;
Musk, AW .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1998, 158 (06) :1724-1729
[4]   Selecting a maximally informative set of single-nucleotide polymorphisms for association analyses using linkage disequilibrium [J].
Carlson, CS ;
Eberle, MA ;
Rieder, MJ ;
Yi, Q ;
Kruglyak, L ;
Nickerson, DA .
AMERICAN JOURNAL OF HUMAN GENETICS, 2004, 74 (01) :106-120
[5]   The Canadian childhood asthma primary prevention study: Outcomes at 7 years of age [J].
Chan-Yeung, M ;
Ferguson, A ;
Watson, W ;
Dimich-Ward, H ;
Rousseau, R ;
Lilley, M ;
DyBuncio, A ;
Becker, A .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2005, 116 (01) :49-55
[6]   A randomized controlled study on the effectiveness of a multifaceted intervention program in the primary prevention of asthma in high-risk infants [J].
Chan-Yeung, M ;
Manfreda, J ;
Dimich-Ward, H ;
Ferguson, A ;
Watson, W ;
Becker, A .
ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE, 2000, 154 (07) :657-663
[7]   PupaSuite: finding functional single nucleotide polymorphisms for large-scale genotyping purposes [J].
Conde, Lucia ;
Vaquerizas, Juan M. ;
Dopazo, Hernan ;
Arbiza, Leonardo ;
Reumers, Joke ;
Rousseau, Frederic ;
Schymkowitz, Joost ;
Dopazo, Joaquin .
NUCLEIC ACIDS RESEARCH, 2006, 34 :W621-W625
[8]  
CURTIS D, 1995, AM J HUM GENET, V56, P811
[9]   Analyses of associations with asthma in four asthma population samples from Canada and Australia [J].
Daley, Denise ;
Lemire, Mathieu ;
Akhabir, Loubna ;
Chan-Yeung, Moira ;
He, Jian Qing ;
McDonald, Treena ;
Sandford, Andrew ;
Stefanowicz, Dorota ;
Tripp, Ben ;
Zamar, David ;
Bosse, Yohan ;
Ferretti, Vincent ;
Montpetit, Alexandre ;
Tessier, Marie-Catherine ;
Becker, Allan ;
Kozyrskyj, Anita L. ;
Beilby, John ;
McCaskie, Pamela A. ;
Musk, Bill ;
Warrington, Nicole ;
James, Alan ;
Laprise, Catherine ;
Palmer, Lyle J. ;
Pare, Peter D. ;
Hudson, Thomas J. .
HUMAN GENETICS, 2009, 125 (04) :445-459
[10]   Pedigree disequilibrium tests for multilocus haplotypes [J].
Dudbridge, F .
GENETIC EPIDEMIOLOGY, 2003, 25 (02) :115-121