''Familial hyperpepsinogenemia'' and Helicobacter pylori infection

OBJECTIVE: Pepsinogen 1 (PG1) is a proenzyme precursor to pepsin, a proteas e secreted by the gastric chief cell. PG1 levels correlate with maximal gas tric acid output. In 1979, Rotter ct al, reported two pedigrees in which el evated PG1 levels and duodenal ulcers were prevalent. They proposed autosom al dominant inheritance of elevated PG1 and suggested that it was a risk fa ctor for duodenal ulcer disease. In 1982, Helicobacter pylori (Hp) was disc overed and was shown to be an important factor in peptic ulcer disease. Hp infection is also associated with increased PGI levels. We tested serum fro m one of the original pedigrees for Hp antibodies to determine whether Hp i nfection could explain the ulcers and elevated PG1 levels. METHODS: ELISA tests were performed using the urease fraction of a crushed Hp extract. Banked serum from one of the original families was thawed and t ested. RESULTS: Of the subjects, 90% (nine of 10) with elevated PG1 were seroposit ive for Hp, compared to only 31% (17 of 55) of those with normal PG1 levels (p < 0.001). The mean PG1 level was higher in the seropositive (94.1 +/- 1 3.3 ng/ml) than the seronegative subjects (54.8 +/- 3.6, p < 0.05). Three o f the four subjects with ulcers were Hpseropositive. The prevalence of Hp-s eropositivity and elevated PG1 declined in parallel in each successive gene ration. When neither parent was seropositive, children were seronegative. CONCLUSIONS: The etiology of elevated PG1 levels in this pedigree is more L ikely due to Helicobacter pylori infection than to a genetic predisposition . (C) 2000 by Am. Cell. of Gastroenterology.