Duodenal Ulcer, Hyperpepsinogenemic I

Human gastric mucosa contains 2 immunochemically distinct types of pepsinogens, I and II. Only pepsinogen I (PG I) is derived exclusively from the chief cells in the oxyntic glands of the gastric body and fundus. The level of PG I in the serum, as determined by radioimmunoassay, correlates with gastric secretory capacity, serves as a marker for the ulcer diathesis, and demonstrates heterogeneity, i.e., a bimodal distribution, in large groups of duodenal ulcer patients. Rotter et al. (1979) found autosomal dominant transmission of elevated serum PG I level in 2 large families with a prominent history of duodenal ulcer. An elevated PG I level identified genetically susceptible but clinically normal persons. About half of sibships with 2 or more cases of duodenal ulcer were found to segregate for high serum PG I. Rotter et al. (1982) did a variance component analysis of the distribution of serum pepsinogen I levels in normal individuals, using a maximum-likelihood method on entire pedigrees. The results indicated a broad heritability of 91%, with some 74% being attributed to a dominance component. The authors felt that pepsinogen I level in normals is principally determined by the action of major genes, as also seems to be the case for duodenal ulcer patients and their families. At least 2 other dominantly inherited syndromes have peptic ulcer as a feature, MEA I with Zollinger-Ellison syndrome (131100) and tremor, nystagmus, and duodenal ulcer (190310).

Helicobacter pylori has more recently become recognized as the predominant cause of peptic ulcer disease. The Lewis blood group antigen, Le(b) (111100), is the epithelial receptor for Helicobacter pylori (Boren et al., 1993). See 600263 for evidence for genetic susceptibility to Helicobacter pylori infection.