title: A plasminogen activator inhibitor-1 promoter polymorphism and idiopathic interstitial pneumonia.
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.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI 48109-0642, USA.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Kim
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Flaherty
authors.forename: Qi
authors.initials: Q
authors.lastname: Long
authors.forename: Noboru
authors.initials: N
authors.lastname: Hattori
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Sisson
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Colby
authors.forename: William D
authors.initials: WD
authors.lastname: Travis
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Martinez
authors.forename: Susan
authors.initials: S
authors.lastname: Murray
authors.forename: Richard H
authors.initials: RH
authors.lastname: Simon
mesh_terms: D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D017395:Plasminogen Activator Inhibitor 1