Association between genetic polymorphism of the pepsinogen C gene and gastric body ulcer: the genetic predisposition is not associated with Helicobacter pylori infection

Abstract

Background and aims-The genetic trait plays a part in the pathogenesis of peptic ulcer disease. To identify a DNA marker for peptic ulcer disease, the association between the restriction fragment length polymorphism (RFLP) of the pepsinogen C (PGC) gene and peptic ulcer disease was investigated. Patients and methods-One hundred and seventy seven unrelated controls, 75 patients with gastric ulcer, and 70 with duodenal ulcer were studied. PGC-RFLP was analysed by polymerase chain reaction (PCR), and the association between PGC-RFLP and peptic ulcer disease was examined. The relation between the genetic association of PGC polymorphism with peptic ulcer and Helicobacter pylori infection was also examined. Results-Four alleles, 480 (allele 1), 450 (allele 2), 400 (allele 3), and 310 bp (allele 4), were detected by PCR. The frequency of allele 4 was significantly higher in patients with gastric body ulcer than in controls ( 2 =9.92, p<0.005). Genotypes containing allele 4 were significantly more frequent in patients with gastric body ulcer than in controls and patients with gastric angular or antral ulcer. The relative risk of gastric body ulcer associated with the presence of allele 4, compared with its absence, was 4.63 and was statistically significant ( 2 =14.84, p<0.005). There were no significant diVerences in the allelic frequencies between H pylori positive and H pylori negative groups in controls, patients with gastric body ulcer, or patients with gastric angular or antral ulcer. Both in H pylori negative and H pylori positive cases, there was an increased frequency of allele 4 in patients with gastric body ulcer compared with controls. Conclusions-These results suggest that there is a significant association between this genetic polymorphism at the PGC gene locus and gastric body ulcer. There are diVerences in the genetic aetiology between gastric body ulcer and gastric angular or antral ulcer. PGC-RFLP may be used as a genetic marker for a genetic predisposition to gastric body ulcer; this genetic predisposition is not associated with H pylori infection. (Gut 1997; 41: 469-474)

Pepsinogen-II 100 bp ins/del gene polymorphism and its elevated circulating levels are associated with gastric cancer, particularly with Helicobacter pylori infection and intestinal metaplasia

“…The results of a Chinese study (57.1-61.0 %) and a Portuguese study (72.4 %) were similar to our observation [7]. However, another Asian study (Japanese: 46.3 %) showed discordance with our findings [6,36]. We also found that carriage of allele 1 (310 bp, the shorter allele) was infrequent among patients with GC compared to HC.…”

“…We observed that allele 1 carriage was infrequent among patients with GC who were seropositive for H. pylori. However, a previous Japanese casecontrol study showed no differences in allelic frequency of PG-II polymorphisms among patients with gastric body ulcer in the presence and absence of H. pylori infection [36]. H. pylori colonizes in the stomach mucosa and increases the risk of GC, being closely related to the level of serum PGs.…”

Biomarkers in Patients with Gastric Inflammation: A Systematic Review

“…Moreover, it should be noted that 20 out of 21 studies demonstrated the reduced level of serum gastrin by H. pylori eradication therapy, suggesting improvement of inflammation in the corpus (table 2) [18, 19, 21, 22,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49]. The level of somatostatin and the number of D cells have been reported to increase after therapy [38, 45,][50], although this requires biopsy specimens for the estimation.…”

Risk factors leading to peptic ulcer disease: systematic review in literature

“…50 Some research results suggest that there is a significant association between genetic polymorphism at the PGR-RFLP gene locus and gastric body ulcer. 51 Genetic play an important role in ulcer pathogenesis. The concordance for peptic ulcer in identical twins is approximately 50%, and the lifetime prevalence of developing ulcer in first degree relatives of ulcer patients is about three-fold greater than in the general population.…”