Genetics of urinary pepsinogen: a new hypothesis

A new genetic model is proposed to explain the inheritance of the urinary pepsinogen (PG1) polymorphism. Each main fraction, 3, 4 and 5, in the multibanded electrophoretic pattern, is determined by its own specific gene, B, C and D respectively. The intensity ratio of the fractions is principally determined by the number of gene copies. Accordingly, the PG1 phenotypes are determined by gene combinations, haplotypes, some of which may be identical to alleles in previous one locus models. Some critical families, not interpretable using previous genetic models, are presented to support the hypothesis. Preliminary population data from the Netherlands are described. The molecular background of this polymorphism and its relevance for gastric (pre)malignancy is discussed.