Association of transforming growth factor-beta1 single nucleotide polymorphism C-509T with allergy and immunological activities.
BACKGROUND
A single nucleotide polymorphism (SNP) C-509T within the tumor growth factor beta1 (TGFbeta1) gene has been associated with atopic asthma and asthma severity. To further understand the mechanisms involved, the association of C-509T with allergy, T-lymphocyte proliferation and plasma TGFbeta1 concentration has been explored in a case-control study with allergic and non-allergic subjects.


METHODS
The recruited subjects including allergic (n = 38) and nonallergic (n = 25) participants have been genotyped for C-509T using allele discrimination assay. Association of C-509T with allergy status was examined using logistic regression analysis in both dominant and recessive models. Association of C-509T with T-cell proliferation in control and antigen-stimulated peripheral blood mononuclear cells (PBMCs), plasma TGFbeta1 and total IgE level were tested by multiple regression analysis.


RESULTS
Individuals with homozygous mutant TT genotype showed a higher risk of allergy (TT: odds ratio = 5.099, 95% confidence limit: 1.355-19.190, p = 0.016) after covariates were adjusted. A trend to increased plasma TGFbeta1 in subjects with T allele has been discovered. In the meantime, the T allele is associated with lower T cell proliferation in controls and maximum response to above antigens. A low T-cell proliferation is correlated with higher plasma TGFbeta1 concentration (p < 0.01). The in vitro studies confirmed the suppressing effect of TGFbeta1 on T-cell proliferation at physiological range. A significant inhibitory effect on IL-4 production was also observed.


CONCLUSIONS
A C to T base change in TGFbeta1 SNP C-509T has been associated with a higher risk of allergy. The mechanisms are not clear. Elevated TGFbeta1 levels associated with the C-509T polymorphism might suppress immune activation as well as Th2 cytokine production.
Meng
Jianfeng
J
Division of Allergy and Clinical Immunology, Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Thongngarm
Torpong
T
Nakajima
Mikio
M
Yamashita
Naomi
N
Ohta
Ken
K
Bates
Christopher A
CA
Grunwald
Gary K
GK
Rosenwasser
Lanny J
LJ
D000483:Alleles; D016022:Case-Control Studies; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics* / Q000276:immunology; D007111:Immunity, Cellular / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000097:blood / Q000187:drug effects / Q000235:genetics*; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation
D016207:Cytokines; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1