Tissue plasminogen activator and plasminogen activator inhibitor type 1 gene polymorphism in patients with gastric ulcer complicated with bleeding.
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.
Kim
Hong-Soo
HS
Department of Internal Medicine, Soonchunhyang University, Chunan Hospital, 23-20 Bongmyungdong, Chonan 330-100, Korea.
Hwang
Kyu-Yoon
KY
Chung
Il-Kwon
IK
Park
Sang-Heum
SH
Lee
Moon-Ho
MH
Kim
Sun-Joo
SJ
Hong
Sae-Yong
SY
D000328:Adult; D000368:Aged; D020087:Alu Elements / Q000235:genetics; D004252:DNA Mutational Analysis; D004381:Duodenal Ulcer / Q000150:complications / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D010438:Peptic Ulcer Hemorrhage / Q000209:etiology / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012008:Recurrence; D017384:Sequence Deletion; D013276:Stomach Ulcer / Q000150:complications / Q000235:genetics*; D010959:Tissue Plasminogen Activator / Q000235:genetics*
D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator