Tissue plasminogen activator and plasminogen activator inhibitor type 1 gene polymorphism in patients with gastric ulcer complicated with bleeding

J Korean Med Sci. 2003 Feb;18(1):58-64. doi: 10.3346/jkms.2003.18.1.58.

Abstract

Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) may be involved in the pathogenesis of peptic ulcers through suppression of fibrinolysis. This study was designed to investigate associations of t-PA and PAI-1 genes with clinical features of the patients with bleeding gastric ulcers. Eighty-four patients with peptic ulcers and 100 controls were studied between January 1998 and April 2000. We used polymerase chain reaction and endonuclease digestion to genotype for 4G/5G polymorphism in the promoter region of the PAI-1 gene and the Alurepeat insertion/deletion (I/D) polymorphism in intron h of the t-PA gene. Various clinical features, including lesion site, bleeding event, recurrence of ulcer, and rebleeding, were assessed using a multiple logistic regression model. The genotype distributions of both the t-PA and PAI-1 genes did not differ between the patient and control groups. The occurrence of the I/D or D/D genotype of t-PA was significantly higher in cases of duodenal ulcer (adjusted OR=4.39, 95% CI=1.12-17.21). When a dominant effect (i.e., 4G/4G or 4G/5G versus 5G/5G) of the 4G allele was assumed, the PAI-1 4G/4G genotype was independently associated with rebleeding after hemostasis (adjusted OR=5.07, 95% CI=1.03-24.87). Our data suggest that t-PA gene polymorphism is associated with duodenal ulcers, and that the PAI-1 gene may be a risk factor leading to recurrent bleeding after initial hemostasis.

MeSH terms

  • Adult
  • Aged
  • Alu Elements / genetics
  • DNA Mutational Analysis
  • Duodenal Ulcer / complications
  • Duodenal Ulcer / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mutagenesis, Insertional
  • Peptic Ulcer Hemorrhage / etiology
  • Peptic Ulcer Hemorrhage / genetics*
  • Plasminogen Activator Inhibitor 1 / genetics*
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic / genetics
  • Recurrence
  • Sequence Deletion
  • Stomach Ulcer / complications
  • Stomach Ulcer / genetics*
  • Tissue Plasminogen Activator / genetics*

Substances

  • Plasminogen Activator Inhibitor 1
  • Tissue Plasminogen Activator