DefinePK

Abstract

Role of genetic factors in the pathogenesis of ulcer has been suggested earlier1. The genetic markers used in the past were ABO blood groups2, secretor and non-secretor st3, HLA typing4 and serum pepsinogen5. Of these, total serum pepsinogen is a better marker of ulcer disease and as reported earlier6, higher values were found among patients with peptic ulcer disease.
Human pepsinogens belong to the group of aspartic proteases and are characterized into two main groups, pepsinogen A and pepsinogen C7. Pepsinogens are inactive forms of pepsins, the Proteolytic enzyme in gastric juice, synthesized in the chief cells of the oxyntic gland area and in. some cells of the pyroric gland area. The peptic cells of the stomach secrete pepsinogen directly into the circulation from which it is removed by the kidneys and excreted as uropepsin8,9.
Analysis of serum pepsinogen is quite re­producible and the individual value fairly constant from day to day has littFe variation in relation to time of day6. The concentrations tends to rise with increasing age upto sixty years10  above which the level declines probably due to increas­ing incidence of atrophic gastritis11 Serum pepsinogen increases in most individuals after betazole12 and pentagastrin stimulation13  In hypersecretory states such as peptic ulcer disease the level increases whereas after total gastrectomy or pernicious anaemia, the concentration declines6.
In duodenal ulcer, elevated concentration appears to be inherited as an autosomal dominant trait. Individuals with this trait have a frequency of duodenal ulcer eight times greater than the general population.14’Serum pepsinogen correlates positively with the level of pepsin in the gastric lumen and contributes to the pathogenesis of an ulcer while the genetically transmitted high levels of serum pepsinogen indicates the presence of an ulcer diathesis15
Serum pepsinogen levels among patients with duodenal ulcer show a bimodal distribution,16 suggesting that the duodenal ulcer patients could be separated into two populations, on the basis of serum pepsinogen level. Duodenal ulcer with hyperpepsinogenaemia may be con­sidered as ‘primary duodenal ulcer’ while an ulcer with normal level be considered as ‘secon­dary duodenal ulcer’. Patients manifesting hyper­pepsinogenaemia require further investigation in the family to indentify siblings and progeny carrying the trait and thus at higher risk15 Studies among the first degree relatives of patients with duodenal ulcer show that an elevated serum pepsinogen level1 is not only associated with duodenal ulcer but also inherited as an autosomal dominant trait. In these studies hyperpepsino­genaemia was found in about 50% of the offspring of family members with elevated serum level and in none of the offspring of normopepsinogenaemic family members. Clinical duodenal ulcer disease was encountered only in relatives with elevated serum pepsinogen level’. Duodenal ulcer patient with normopepsinogenaemia may safely be con­sidered to be suffering from nongenetic or ‘secondary duodenal ulcer’ and these ulcers are the result of neuroendocrinological or environmental factors which are also known to cause ulcer disease15
Thus an elevated pepsinogen level may prove to be a valuable subclinical marker of duodenal ulcer disease.