Document Detail


Transforming growth factor-beta1 promoter polymorphism C-509T is associated with asthma.
MedLine Citation:
PMID:  14597484     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Transforming growth factor-beta1 (TGF-beta1) is increased in the lungs of individuals with asthma and may modulate airway inflammation and remodeling. Some genetic studies have found that a C-to-T single-nucleotide polymorphism (C-509T) in the TGF-beta1 gene promoter may be associated with altered gene expression and asthma phenotype. To build on these data, we performed a case-control association study at this locus involving 527 subjects with asthma and 170 control subjects without asthma. All individuals were white. Genotyping at 49 unlinked polymorphisms indicated that a subset of case subjects and all control subjects were well matched and without evidence of population stratification. Logistic regression was used to model the effects of age, sex, and genotype on case-control status. The diagnosis of asthma was positively associated with the T allele and TT genotype under a codominant model (odds ratio, 2.98; 95% confidence interval, 1.45 to 6.25; p = 0.003). Total serum IgE, eosinophil count, and FEV1% predicted levels were not associated with this polymorphism. Furthermore, we show that the C-509T polymorphism alters TGF-beta1 promoter-reporter activity and promoter interactions with the transcription factor Yin Yang 1. We conclude that the T allele of C-509T is associated with the diagnosis of asthma and may enhance TGF-beta1 gene transcription.
Authors:
Eric S Silverman; Lyle J Palmer; Venkat Subramaniam; Arlene Hallock; Sheeba Mathew; Joseph Vallone; Debora S Faffe; Toshiki Shikanai; Benjamin A Raby; Scott T Weiss; Stephanie A Shore
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2003-11-03
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  169     ISSN:  1073-449X     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2004 Jan 
Date Detail:
Created Date:  2004-01-13     Completed Date:  2004-02-12     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  214-9     Citation Subset:  AIM; IM    
Affiliation:
Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA. esilverm@hsph.harvard.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
Asthma / genetics*,  physiopathology
Case-Control Studies
DNA-Binding Proteins / genetics
Erythroid-Specific DNA-Binding Factors
Female
Gene Frequency
Genotype
Humans
Male
Polymorphism, Single Nucleotide*
Promoter Regions, Genetic / genetics*
Transcription Factors / genetics
Transforming Growth Factor beta / genetics*
Transforming Growth Factor beta1
YY1 Transcription Factor
Grant Support
ID/Acronym/Agency:
HL70573/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Erythroid-Specific DNA-Binding Factors; 0/TGFB1 protein, human; 0/Transcription Factors; 0/Transforming Growth Factor beta; 0/Transforming Growth Factor beta1; 0/YY1 Transcription Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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