View : 23 Download: 0

T-bet polymorphisms are associated with asthma and airway hyperresponsiveness

Title
T-bet polymorphisms are associated with asthma and airway hyperresponsiveness
Authors
Raby, BAHwang, ESVan Steen, KTantisira, KPeng, SLitonjua, ALazarus, RGiallourakis, CRioux, JDSparrow, DSilverman, EKGlimcher, LHWeiss, ST
Ewha Authors
황은숙
SCOPUS Author ID
황은숙scopus
Issue Date
2006
Journal Title
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
ISSN
1073-449XJCR Link
Citation
vol. 173, no. 1, pp. 64 - 70
Keywords
immunoglobulin Esingle nucleotide polymorphismT-boxTBX21
Publisher
AMER THORACIC SOC
Indexed
SCI; SCIE; SCOPUS WOS
Abstract
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 nucleoticle 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 PC20, 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 SNIPS, 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.
DOI
10.1164/rccm.200503-505OC
Appears in Collections:
약학대학 > 약학과 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE