Genetic and evolutionary implications in peptic ulcer disease

Abstract

The evidence for a genetic component in peptic ulcer disease has been based on twin, family, and blood group studies. A polygenic model for the inheritance of peptic ulcers has been displaced by a genetic heterogeneity model based on several lines of evidence, some of the most powerful being recent work using subclinical markers. One marker in particular, an elevated level of serum pepsinogen I (PG I), a pepsin precursor produced by the gastric mucosa, secreted into the stomach lumen and also appearing in the bloodstream, has been found to be associated with a subgroup of duodenal ulcer patients. Segregation analysis of elevated serum PG I in duodenal ulcer sibships demonstrates familial aggregation consistent with autosomal dominant inheritance. Elevated PG I is also accompanied by gastric hyperacidity and presumably indicates those individuals with an increased mass of chief and parietal cells, and thus an increased capacity for peptic activity, an important element in the pathogenesis of ulcer disease. An evolutionary hypothesis based on selection for peptic activity and acidity is offered to explain several of the epidemiologic and genetic elements of this group of chronic diseases.