A plasminogen activator inhibitor-1 promoter polymorphism and idiopathic interstitial pneumonia

Kevin K. Kim, Kevin R. Flaherty, Qi Long, Noboru Hattori, Thomas H. Sisson, Thomas V. Colby, William D. Travis, Fernando J. Martinez, Susan Murray, Richard H. Simon

Research output: Contribution to journalArticle

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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 PAI-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 PAI-1 genotype.

Original languageEnglish (US)
Pages (from-to)52-56
Number of pages5
JournalMolecular Medicine
Volume9
Issue number1-2
StatePublished - Jan 2003

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Idiopathic Interstitial Pneumonias
Plasminogen Activator Inhibitor 1
Genotype
Idiopathic Pulmonary Fibrosis
Interstitial Lung Diseases
Pulmonary Fibrosis
Population
Lung Diseases
Plasminogen
DNA Restriction Enzymes
Genetic Promoter Regions
Paraffin
Digestion

ASJC Scopus subject areas

  • Genetics

Cite this

Kim, K. K., Flaherty, K. R., Long, Q., Hattori, N., Sisson, T. H., Colby, T. V., ... Simon, R. H. (2003). A plasminogen activator inhibitor-1 promoter polymorphism and idiopathic interstitial pneumonia. Molecular Medicine, 9(1-2), 52-56.

A plasminogen activator inhibitor-1 promoter polymorphism and idiopathic interstitial pneumonia. / Kim, Kevin K.; Flaherty, Kevin R.; Long, Qi; Hattori, Noboru; Sisson, Thomas H.; Colby, Thomas V.; Travis, William D.; Martinez, Fernando J.; Murray, Susan; Simon, Richard H.

In: Molecular Medicine, Vol. 9, No. 1-2, 01.2003, p. 52-56.

Research output: Contribution to journalArticle

Kim, KK, Flaherty, KR, Long, Q, Hattori, N, Sisson, TH, Colby, TV, Travis, WD, Martinez, FJ, Murray, S & Simon, RH 2003, 'A plasminogen activator inhibitor-1 promoter polymorphism and idiopathic interstitial pneumonia', Molecular Medicine, vol. 9, no. 1-2, pp. 52-56.
Kim KK, Flaherty KR, Long Q, Hattori N, Sisson TH, Colby TV et al. A plasminogen activator inhibitor-1 promoter polymorphism and idiopathic interstitial pneumonia. Molecular Medicine. 2003 Jan;9(1-2):52-56.
Kim, Kevin K. ; Flaherty, Kevin R. ; Long, Qi ; Hattori, Noboru ; Sisson, Thomas H. ; Colby, Thomas V. ; Travis, William D. ; Martinez, Fernando J. ; Murray, Susan ; Simon, Richard H. / A plasminogen activator inhibitor-1 promoter polymorphism and idiopathic interstitial pneumonia. In: Molecular Medicine. 2003 ; Vol. 9, No. 1-2. pp. 52-56.
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