TGFB1 promoter polymorphism C-509T and pathophysiology of asthma.
BACKGROUND
TGF-beta1 can modulate airway inflammation and exaggerate airway remodeling. A polymorphism of a promoter region of TGFB1, C-509T, might be associated with the development of asthma, but its pathophysiologic relevance remains poorly understood.


OBJECTIVE
We investigated relations of the C-509T polymorphism to airflow obstruction, sputum eosinophilia, and airway wall thickening, as assessed by means of computed tomography, in 85 patients with stable asthma.


METHODS
The CC, CT, and TT genotypes were examined by means of PCR and restriction enzyme fragment length polymorphism. At a selected bronchus, 3 indices of airway wall thickness were measured with an automatic method.


RESULTS
The CC, CT, and TT genotypes were found in 22, 46, and 17 patients, respectively. Serum TGF-beta1 levels were significantly associated with the polymorphism and were increased in the CT/TT genotypes. FEV(1) and sputum eosinophil percentages were also significantly associated with the polymorphism and were both decreased in the CT/TT genotypes. The polymorphism was unrelated to airway wall thickness.


CONCLUSIONS
In addition to increased serum TGF-beta1 levels, the T allele of the C-509T polymorphism is related to increased airflow obstruction but attenuated eosinophilic inflammation. The former relation is not attributed to thickening of the central airway walls. The latter relation might reflect the anti-inflammatory effect of TGF-beta1. The C-509T polymorphism has a complex role in asthma pathophysiology, presumably because of the diverse functions of TGF-beta1 and its various interactions with cells and humoral factors in vivo.
Ueda
Tetsuya
T
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Niimi
Akio
A
Matsumoto
Hisako
H
Takemura
Masaya
M
Yamaguchi
Masafumi
M
Matsuoka
Hirofumi
H
Jinnai
Makiko
M
Chin
Kazuo
K
Minakuchi
Masayoshi
M
Cheng
Lei
L
Shirakawa
Taro
T
Mishima
Michiaki
M
D001249:Asthma / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D001980:Bronchi / Q000473:pathology; D004804:Eosinophils / Q000166:cytology / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012129:Respiratory Function Tests; D013183:Sputum / Q000166:cytology / Q000276:immunology; D014057:Tomography, X-Ray Computed; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000235:genetics*
C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1