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

BACKGROUND/AIMS: Tumor necrosis factor alpha (TNF-alpha) encoded by TNFA is a key mediator in inflammation, a precursor condition for peptic ulceration. Promoter polymorphisms of TNFA that influence its transcriptional activity and TNF-alpha production are known. TNFA-308G>A (rs1800629) and TNFA-1031T>C (rs1799964), which are responsible for increased TNFA transcription, could influence the risk of peptic ulceration. This study aimed to investigate these polymorphisms and to evaluate their association with peptic ulcer disease and Helicobacter pylori infection in the Polish population. METHODS: Gastric mucosa specimens obtained from 177 Polish peptic ulcer patients were used to conduct rapid urease tests and to assess the investigated polymorphisms by polymerase chain reaction-restriction fragment length polymorphism. Genotyping data were compared with the results obtained from healthy individuals of Polish origin. RESULTS: There were no significant differences in genotype and allele frequency of the investigated polymorphisms between peptic ulcer patients and healthy individuals. No associations between the frequencies of particular genotypes and alleles for both single-nucleotide polymorphisms (SNPs) and the presence of H. pylori infection in peptic ulcer patients and in subgroups of men and women with peptic ulcer disease were found. CONCLUSIONS: The investigated SNPs are not risk factors for either peptic ulcer or H. pylori infection development in the Polish population. The results require verification in a larger cohort.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; European Continental Ancestry Group/genetics ; Female ; Gastric Mucosa/*metabolism/microbiology ; Genetic Predisposition to Disease ; Genotype ; Helicobacter Infections/complications/*genetics ; Helicobacter pylori ; Humans ; Male ; Middle Aged ; Peptic Ulcer/complications/*genetics ; Poland ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; *Promoter Regions, Genetic ; Tumor Necrosis Factor-alpha/*genetics ; Young Adult