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 β1 (TGF-β1) and tumor necrosis factor α (TNF-α) in asthma is unclear. The aim of this study was to assess the relationships among polymorphisms, clinical phenotypes, and the serum levels of TGF-β1 and TNF-α. METHODS Polymorphisms of promoter of TGF-β1 (C-509T locus) and TNF-α (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-β1, and TNF-α were assessed. RESULTS The genetic polymorphisms of TGF-β1 promoter and TNF-α were significantly associated with asthma. Subjects with more severe asthma had higher serum levels of TGF-β1 and TNF-α. In asthmatic subjects the TGF-β1 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-β1 or TNF-α. The high values of TGF-β1 or TNF-α were defined by higher than the mean values of the studied subjects of TGF-β1 (392.42 pg/mL) and TNF-α (55.86 pg/mL). The FEV1 of the group with high TGF-β1 plus low TNF-α was lower than that in the group with low TGF-β1 plus low TNF-α. The lowest FEV1 was in the group with high TNF-α and high TGF-β1. CONCLUSIONS The genetic polymorphisms of TGF-β1 and TNF-α are associated with asthma. TGF-β1 modulates atopy. Both TGF-β1 and TNF-α modulate clinical severity and airway obstruction, in an additive manner.