ASSOCIATION BETWEEN GENETIC-POLYMORPHISM OF THE PEPSINOGEN-C GENE ANDGASTRIC BODY ULCER - THE GENETIC PREDISPOSITION IS NOT ASSOCIATED WITH HELICOBACTER-PYLORI INFECTION

Background and aims-The genetic trait plays a part in the pathogenesis of peptic ulcer disease. To identify a DNA marker for peptic ulcer di sease, the association between the restriction fragment length polymor phism (RFLP) of the pepsinogen C (PGC) gene and peptic ulcer disease w as investigated. Patients and methods-One hundred and seventy seven un related controls, 75 patients with gastric ulcer, and 70 with duodenal ulcer were studied. PGC-RFLP was analysed by polymerase chain reactio n (PCR), and the association between PGC-RFLP and peptic ulcer disease was examined. The relation between the genetic association of PGC pol ymorphism 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 ulc er than in controls (chi(2) = 9.92, p < 0.005). Genotypes containing a llele 4 were significantly more frequent in patients with gastric body ulcer than in controls and patients with gastric angular or antral ul cer. The relative risk of gastric body ulcer associated with the prese nce of allele 4, compared with its absence, was 4.63 and was statistic ally significant (chi(2) = 14.84, p < 0.005). There were no significan t differences in the allelic frequencies between H pylori positive and H pylori negative groups in controls, patients with gastric body ulce r, 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 control s. Conclusions-These results suggest that there is a significant assoc iation between this genetic polymorphism at the PGC gene locus and gas tric body ulcer. There are differences in the genetic aetiology betwee n gastric body ulcer and gastric angular or antral ulcer. PGC-RFLP may be used as a genetic marker for a genetic predisposition to gastric b ody ulcer; this genetic predisposition is not associated with H pylori infection.