Genetic Polymorphism of Transforming Growth Factor β1 and Tumor Necrosis Factor α Is Associated With Asthma and Modulates the Severity of Asthma

BACKGROUND: The role of transforming growth factor beta 1 (TGF-beta 1) and tumor necrosis factor a (TNF-alpha) in asthma is unclear. The aim of this study was to assess the relationships among polymorphisms, clinical phenotypes, and the serum levels of TGF-beta 1 and TNF-alpha. METHODS: Polymorphisms of promoter of TGF-beta 1 (C-509T locus) and TNF-alpha (G-308 A locus; rs 1800629) in 217 asthmatic patients and 110 healthy controls were evaluated. Pulmonary function, total immunoglobulin E (IgE), specific IgE antibodies, total eosinophil counts, TGF-beta 1, and TNF-alpha were assessed. RESULTS: The genetic polymorphisms of TGF-beta 1 promoter and TNF-alpha were significantly associated with asthma. Subjects with more severe asthma had higher serum levels of TGF-beta 1 and TNF-alpha. In asthmatic subjects the TGF-beta 1 of atopic subjects was higher than those without atopy. All studied subjects (asthma plus control) were divided into 4 groups by mean value of TGF-beta 1 or TNF-alpha. The high values of TGF-beta 1 or TNF-alpha were defined by higher than the mean values of the studied subjects of TGF-beta 1 (392.42 pg/mL) and TNF-alpha (55.86 pg/mL). The FEV1 of the group with high TGF-beta 1 plus low TNF-alpha was lower than that in the group with low TGF-beta 1 plus low TNF-alpha. The lowest FET1 was in the group with high TNF-alpha and high TGF-beta 1. CONCLUSIONS: The genetic polymorphisms of TGF-beta 1 and TNF-alpha are associated with asthma. TGF-beta 1 modulates atopy. Both TGF-beta 1 and TNF-alpha modulate clinical severity and airway obstruction, in an additive manner.