Association of Transforming Growth Factor-β1 Single Nucleotide Polymorphism C-509T with Allergy and Immunological Activities

Abstract

Listen

Translate article

Background: A single nucleotide polymorphism (SNP) C-509T within the tumor growth factor β1 (TGFβ1) 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 TGFβ1 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 TGFβ1 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 TGFβ1 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 TGFβ1 concentration (p < 0.01). The in vitro studies confirmed the suppressing effect of TGFβ1 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 TGFβ1 SNP C-509T has been associated with a higher risk of allergy. The mechanisms are not clear. Elevated TGFβ1 levels associated with the C-509T polymorphism might suppress immune activation as well as Th2 cytokine production.