A plasminogen activator inhibitor-1 promoter polymorphism and idiopathic interstitial pneumonia. Academic Article uri icon

Overview

MeSH

  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Male
  • Middle Aged

MeSH Major

  • Lung Diseases, Interstitial
  • Plasminogen Activator Inhibitor 1
  • Polymorphism, Genetic
  • Promoter Regions, Genetic

abstract

  • The normal fibrinolytic activity within the alveolar space is suppressed in fibrotic lung diseases in part because of increased levels of plasminogen activator inhibitor-1 (PAI-1). Studies with animals have shown that inhibition of the plasminogen system by PAI-1 increases the generation of pulmonary fibrosis. To determine if a similar relationship occurs in human fibrotic lung diseases, we took advantage of a polymorphism (4G/5G) that occurs in the promoter region of the human PAI-1 gene and influences the expression of PAI-1. We hypothesized that the 4G/4G genotype, because of its association with higher levels of PAI-1, would occur in patients with idiopathic interstitial pneumonia more frequently than in a control population. PAI-1 promoter genotype was determined in 88 well-characterized patients with idiopathic interstitial pneumonia consisting of 62 patients with usual interstitial pneumonia and 26 with nonspecific interstitial pneumonia. DNA was extracted from paraffin-embedded biopsy tissue and the genotype identified by polymerase chain reaction and restriction endonuclease digestion. We found that the distribution of PAI-1 genotypes in the idiopathic interstitial pneumonia population was similar to that of a large control population. However, subgroup analysis showed that patients with nonspecific interstitial pneumonia were more likely than the control population to have the promoter genotype (4G/4G) that is associated with higher levels of PAI-1. A similar pattern in PAI-1 polymorphism was not seen in the usual interstitial pneumonia subgroup. The results of this study support the conclusion that PAl-1 expression influences the development of nonspecific interstitial pneumonia in a similar manner to what occurs in animal models of pulmonary fibrosis. Patients with usual interstitial pneumonia did not show the same relationship with PAl-1 genotype.

publication date

  • February 2003
  • January 2003

has subject area

  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Lung Diseases, Interstitial
  • Male
  • Middle Aged
  • Plasminogen Activator Inhibitor 1
  • Polymorphism, Genetic
  • Promoter Regions, Genetic

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1430380

PubMed ID

  • 12765340

Additional Document Info

start page

  • 52

end page

  • 56

volume

  • 9

number

  • 1-2