Genetic polymorphism of transforming growth factor β1 and tumor necrosis factor α is associated with asthma and modulates the severity of asthma

Respir Care. 2013 Aug;58(8):1343-50. doi: 10.4187/respcare.02187. Epub 2013 Mar 6.

Abstract

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.

Keywords: asthma; phenotype; transforming growth factor β1; tumor necrosis factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Airway Obstruction / genetics
  • Asthma / genetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic
  • Polymorphism, Restriction Fragment Length
  • Severity of Illness Index
  • Transforming Growth Factor beta1 / blood
  • Transforming Growth Factor beta1 / genetics*
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / genetics*
  • Young Adult

Substances

  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha