Genetics of pepsinogen I

Abstract

A study of 948 Norwegians including 118 matings with 429 children provided evidence that the Pg I group of pepsinogens must be coded for by more than one gene locus. At the Pg5 locus the alleles Pg5N, Pg5F and Pg5S with frequencies 0.644, 0.059 and 0.004, each code for a single electrophoretic isozyme band responsible for Pg phenotypes Pg 5, intense Pg (4) and Pg 5S, and a null-allele Pg5o with frequency 0.293. The Pg 2, Pg 3 and weak Pg 4 bands are not coded for by alleles at the Pg5 locus and differ from the Pg5 gene products in the oligopeptides split off by pepsinogen-pepsin conversion. The Pg5 alleles differ from each other in the pepsin-coding part of the gene. Intensity variations of Pg 5 have no simple genetic explanation.

New detection method for uropepsinogen (PGA) using isoelectric focusing and immunoblotting techniques

“…PGA isozymogen was clearly separated and detected on the gel by a new combination technique utilizing both IEF and subsequent immunoblotting with the PGA-specific antibody. This technique provided higher resolution for PGA isozymogen analyses than those based on either ordinary electrophoresis on agar or polyacrylamide gels and those following detection of proteolytic activity of the isozymogen after acid activation, reported by other investigators [3][4][5][6]. Therefore, the present method facilitates a much clearer degree of discrimination between PGA phenotypes, and thus is greatly advantageous for the genetic study of PGA.…”

“…Genetic models of PGA have been proposed by several investigators [3][4][5][6][7], who have used all the proteolytic properties of acid-activated PGA for the detection of the isozymogens on agar or polyacrylamide gels. However, immunologic detection of PGA isozymogen is more important for genetic analysis, since the term, PGA, is immunochemically based on the pepsinogen grouping.…”

Human pepsinogen A (PGA): an informative gene complex located at 11q13

“…Human pepsinogen has been known to be a complicated protein polymorphism for almost 20 years (Samloff and Townes 1970a, b). It was clear from studies conducted prior to the advent of molecular probes that genetic variation was a major determinant of the observed protein heterogeneity (Samloff and Townes 1970a, b;Weitkamp and Townes 1975;Taggart et al 1979;Korsnes and Gedde-Dahl 1980;Frants et al 1984). Recent molecular studies with cDNA probes have provided evidence that pepsinogen haplotypes containing different combinations of genes are the major contributing factor in the observed protein heterogeneity (Taggart et al 1985Zelle et al 1985;Evers et al 1987;Bebelman et al 1989).…”

Variable numbers of pepsinogen genes are located in the centromeric region of human chromosome 11 and determine the high-frequency electrophoretic polymorphism.

“…Individuals homozygous for the alternative allele, pgb, did not exhibit Pg 5 activity (designated phenotype B). In addition to the absence of Pg 5, variations in the intensity of the other PGA isozymogens were subsequently reported by several investigators (3)(4)(5). Recent studies of several rare PG I variants in the Dutch population have provided evidence for the existence of multiple genes for PG I (7).…”

“…These electrophoretically distinguishable pepsin precursors exhibit extensive intensity variation of the individual isozymogens Pg 5, Pg 4, Pg 3, and Pg 2. Initial family studies of urinary pepsinogen phenotypes were unable to determine whether the polymorphic variation of the individual isozymogens resulted from multigenic or allelic variation (2)(3)(4)(5). A major difficulty for the genetic and biochemical characterization of these closely related proteins has been the inability to detect a defined molecular difference among them beyond that observed by electrophoresis.…”