Article (Scientific journals)
T-bet polymorphisms are associated with asthma and airway hyperresponsiveness
Raby, B. A.; Hwang, E. S.; Van Steen, Kristel et al.
2006In American Journal of Respiratory and Critical Care Medicine, 173 (1), p. 64-70
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Keywords :
Adolescent; Adult; Aged; Asthma/*genetics; Bronchial Hyperreactivity/*genetics; Child; Child, Preschool; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Phenotype; Polymorphism, Single Nucleotide; T-Box Domain Proteins/*genetics
Abstract :
[en] RATIONALE: T-bet (TBX21 or T-box 21) is a critical regulator of T-helper 1 lineage commitment and IFN-gamma production. Knockout mice lacking T-bet develop airway hyperresponsiveness (AHR) to methacholine, peribronchial eosinophilic and lymphocytic inflammation, and increased type III collagen deposition below the bronchial epithelium basement membrane, reminiscent of both acute and chronic asthma histopathology. Little is known regarding the role of genetic variation surrounding T-bet in the development of human AHR. OBJECTIVES: To assess the relationship between T-bet polymorphisms and asthma-related phenotypes using family-based association. METHODS: Single nucleotide polymorphism discovery was performed by resequencing the T-bet genomic locus in 30 individuals (including 22 patients with asthma). Sixteen variants were genotyped in 580 nuclear families ascertained through offspring with asthma from the Childhood Asthma Management Program clinical trial. Haplotype patterns were determined from this genotype data. Family-based tests of association were performed with asthma, AHR, lung function, total serum immunoglobulin E, and blood eosinophil levels. MAIN RESULTS: We identified 24 variants. Evidence of association was observed between c.-7947 and asthma in white families using both additive (p = 0.02) or dominant models (p = 0.006). c.-7947 and three other variants were also associated with AHR (log-methacholine PC(20), p = 0.02-0.04). Haplotype analysis suggested that an AHR locus is in linkage disequilibrium with variants in the 3'UTR. Evidence of association of AHR with c.-7947, but not with other 3'UTR SNPs, was replicated in an independent cohort of adult males with AHR. CONCLUSIONS: These data suggest that T-bet variation contributes to airway responsiveness in asthma.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Raby, B. A.
Hwang, E. S.
Van Steen, Kristel  ;  Université de Liège - ULiège > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Bioinformatique
Tantisira, K.
Peng, S.
Litonjua, A.
Lazarus, R.
Giallourakis, C.
Rioux, J. D.
Sparrow, D.
Silverman, E. K.
Glimcher, L. H.
Weiss, S. T.
More authors (3 more) Less
Language :
English
Title :
T-bet polymorphisms are associated with asthma and airway hyperresponsiveness
Publication date :
2006
Journal title :
American Journal of Respiratory and Critical Care Medicine
ISSN :
1073-449X
eISSN :
1535-4970
Publisher :
American Thoracic Society, New York, United States - New York
Volume :
173
Issue :
1
Pages :
64-70
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
2005/09/24
Available on ORBi :
since 24 May 2010

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