Transforming growth factor-beta(2) polymorphisms are associated with childhood atopic asthma.
BACKGROUND
Transforming growth factor (TGF)-beta plays an important role in the regulation of airway inflammation and remodelling in asthma. Recent studies suggest that TGF-beta(2) is a predominant isoform expressed in severe asthma and it is also associated with airway remodelling.


OBJECTIVE
To determine whether the polymorphisms in TGF-beta(2) are associated with childhood atopic bronchial asthma in a Japanese population.


METHODS
We identified a total of eight polymorphisms and characterized the linkage disequilibrium (LD) mapping of the gene. Three variants in the promoter and 3'UTR were genotyped, and we conducted an association study of TGF-beta(2) (childhood atopic asthma n=297, normal controls n=555). An association analysis of these variants and an expression and functional analysis were performed.


RESULTS
3'UTR 94862T >A was found to be significantly associated with the risk of childhood atopic asthma (P=0.00041). The -109-->ACAA ins promoter variant was also associated with the risk of childhood atopic asthma (P=0.0037). TGF-beta(2) expression was observed in both the normal and asthmatic bronchial epithelium, and both real-time PCR and an ELISA showed a significant basal and TGF-beta(1)-induced TGF-beta(2) expression in the bronchial epithelial cell line BEAS2B. Furthermore, the promoter variant -109-->ACAA ins increased the TGF-beta(2) promoter-reporter activity in BEAS2B cells.


CONCLUSIONS
Our data suggest that TGF-beta(2) may therefore be involved in the development of childhood atopic asthma by means of functional genetic polymorphism. The polymorphisms in TGF-beta(2) may become important information for asthma susceptibility in children.
Hatsushika
K
K
Department of Immunology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Hirota
T
T
Harada
M
M
Sakashita
M
M
Kanzaki
M
M
Takano
S
S
Doi
S
S
Fujita
K
K
Enomoto
T
T
Ebisawa
M
M
Yoshihara
S
S
Sagara
H
H
Fukuda
T
T
Masuyama
K
K
Katoh
R
R
Matsumoto
K
K
Saito
H
H
Ogawa
H
H
Tamari
M
M
Nakao
A
A
D020413:3' Untranslated Regions / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People; D001249:Asthma / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D053781:Transforming Growth Factor beta2 / Q000096:biosynthesis / Q000235:genetics*
D020413:3' Untranslated Regions; D053781:Transforming Growth Factor beta2