Transforming growth factor-β1 and tumor necrosis factor-α are associated with clinical severity and airflow limitation of COPD in an additive manner

Lung. 2014 Feb;192(1):95-102. doi: 10.1007/s00408-013-9520-2. Epub 2013 Oct 24.

Abstract

Background: The role of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) in chronic obstructive pulmonary disease (COPD) is controversial. The purpose of this study was to assess the relationships among polymorphisms, clinical phenotypes, and the serum levels of TNF-α and TGF-β1.

Methods: Polymorphisms of promoters of TNF-α (rs 361525 and rs 1800629) and TGF-β1 (rs 1800469) in 110 COPD patients, 110 nonsmoker health controls without COPD, and 34 smokers were evaluated. Pulmonary functions, chest computed tomography, TGF-β1, and TNF-α were assessed.

Results: The genetic polymorphism of TNF-α (rs 361525) was associated with COPD. More severe COPD patients had higher serum levels of TNF-α and TGF-β1; moreover, serum levels of TGF-β1of mild COPD patients were higher than normal controls. All of the studied subjects were divided into four groups by the 95th percentile value of control as cutoff serum value of TGF-β1 (224.35 ρg/ml) or TNF-α (17.56 ρg/ml) to define the high value of TGF-β1 or TNF-α, which are higher than those cutoff of values (>224.35 or 17.56 ρg/ml). The FEV1 of the group with high TGF-β1 + low TNF-α or low TGF-β1 + high TNF-α or high TNF-α + high TGF-β1 was lower than the group with low TGF-β1 + low TNF-α group. Moreover, the lowest value of FEV1 was in the group with high TNF-α + high TGF-β1.

Conclusions: The genetic polymorphism of the TNF-α is associated with COPD. Both TGF-β1 and TNF-α modulate clinical severity and airflow limitation in an additive manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Forced Expiratory Volume
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Humans
  • Lung / diagnostic imaging
  • Lung / physiopathology*
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic
  • Predictive Value of Tests
  • Promoter Regions, Genetic
  • Pulmonary Disease, Chronic Obstructive / blood
  • Pulmonary Disease, Chronic Obstructive / diagnosis*
  • Pulmonary Disease, Chronic Obstructive / diagnostic imaging
  • Pulmonary Disease, Chronic Obstructive / genetics
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Respiratory Function Tests
  • Risk Factors
  • Severity of Illness Index
  • Tomography, X-Ray Computed
  • Transforming Growth Factor beta1* / blood
  • Transforming Growth Factor beta1* / genetics
  • Tumor Necrosis Factor-alpha* / blood
  • Tumor Necrosis Factor-alpha* / genetics
  • Vital Capacity

Substances

  • Genetic Markers
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha