Human pepsinogens: A review of clinical and genetic aspects

In recent years clinical interest in the study of the proteolytic enzymes of the stomach has greatly increased. Human pepsinogens belong to the group of aspartic proteases and are categorized into two main groups: Pepsinogen A (PGA = PG I) and Pepsinogen C (PGC = PG II). Genetic models have been proposed to explain the inheritance of PGA, and a recent multigene model may be of value. PGA phenotypes in urine and gastric mucosa have been determined in healthy volunteers as well as in patients with different gastric disorders. An increased frequency of the ‘intense Pg5’ phenotype seems to be associated with gastric cancer and pre-malignant conditions, such as atrophic gastritis. Reliable radio-immunoassay and enzyme-linked immunosorbent assay techniques have facilitated the study of serum levels of PGA and PGC in different patient groups; in particular, duodenal ulcer patients (high PGA levels) and patients with atrophic gastritis and/or gastric cancer (low PGA levels). The ratio serum PGA/PGC may be introduced for clinical application, being the most convenient non-invasive marker for the detection of fundic atrophy. While the chromosome localization of pepsinogen has been established, further research is likely to concentrate on the structure and organization of the pepsinogen genes at the DNA-level, as well as on the development of new isozyme specific monoclonal antibodies.