Transforming growth factor-beta1 promoter polymorphism C-509T is associated with asthma.
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.
Silverman
Eric S
ES
Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115, USA. esilverm@hsph.harvard.edu
Palmer
Lyle J
LJ
Subramaniam
Venkat
V
Hallock
Arlene
A
Mathew
Sheeba
S
Vallone
Joseph
J
Faffe
Debora S
DS
Shikanai
Toshiki
T
Raby
Benjamin A
BA
Weiss
Scott T
ST
Shore
Stephanie A
SA
D000328:Adult; D001249:Asthma / Q000235:genetics* / Q000503:physiopathology; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics; D050981:Erythroid-Specific DNA-Binding Factors; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1; D050986:YY1 Transcription Factor
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; C508960:TGFB1 protein, human; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D050986:YY1 Transcription Factor