Transforming growth factor-beta1 gene polymorphisms are associated with disease progression in idiopathic pulmonary fibrosis

Am J Respir Crit Care Med. 2003 Aug 15;168(4):431-5. doi: 10.1164/rccm.200210-1165OC. Epub 2003 May 13.


Transforming growth factor-beta1 (TGF-beta1) is a cytokine that plays a key role in the development of idiopathic pulmonary fibrosis. There have been reports on the presence of two genetic polymorphisms in the DNA sequence encoding the leader sequence of the TGF-beta1 protein, located in codons 10 and 25. The objective of this study was to investigate the association between TGF-beta1 gene polymorphisms in codons 10 and 25 and the susceptibility to idiopathic pulmonary fibrosis and the progression of the disease. Compared with healthy control subjects (n = 140), patients with idiopathic pulmonary fibrosis (n = 128) showed no significant deviations in genotype or allele frequencies. One hundred and ten patients with idiopathic pulmonary fibrosis were followed up for 30.3 +/- 25 months. The presence of a proline allele at codon 10 was independently associated with a significant increase in alveolar arterial oxygen tension difference during follow-up, after controlling for the effect of treatment (coefficient = 0.59; 95% confidence intervals, 0.23 to 0.96; p = 0.002). These findings suggest that (1) TGF-beta1 gene polymorphisms in codons 10 and 25 do not predispose to the development of idiopathic pulmonary fibrosis; and (2) TGF-beta1 gene polymorphisms may affect disease progression in patients with idiopathic pulmonary fibrosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Base Sequence / genetics
  • Chi-Square Distribution
  • Codon / genetics
  • Confidence Intervals
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Gene Frequency / genetics
  • Genotype
  • Humans
  • Linear Models
  • Male
  • Oxygen / blood
  • Polymorphism, Genetic / genetics*
  • Proline / genetics
  • Pulmonary Alveoli / metabolism
  • Pulmonary Fibrosis / drug therapy
  • Pulmonary Fibrosis / genetics*
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta1


  • Codon
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Proline
  • Oxygen