Literature DB >> 16179826

Association of transforming growth factor-beta1 single nucleotide polymorphism C-509T with allergy and immunological activities.

Jianfeng Meng1, Torpong Thongngarm, Mikio Nakajima, Naomi Yamashita, Ken Ohta, Christopher A Bates, Gary K Grunwald, Lanny J Rosenwasser.   

Abstract

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. (c) 2005 S. Karger AG, Basel

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Year:  2005        PMID: 16179826     DOI: 10.1159/000088437

Source DB:  PubMed          Journal:  Int Arch Allergy Immunol        ISSN: 1018-2438            Impact factor:   2.749


  7 in total

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