Background and objective: Human pepsinogen C (PGC) is an aspartic protease synthesized in gastric mucosa. PGC gene insertion/deletion polymorphism, which is located between exon 7 and 8, has been found to associate with gastric cancer (GC) susceptibility. This study was to investigate the relationship between PGC polymorphism with protein expression of PGC in gastric mucosa and serum.
Methods: PGC insertion/deletion polymorphism was evaluated by PCR, followed by direct DNA sequencing in 493 cases of GC, atrophic gastritis (AG), gastric erosion ulcer (GEU) and superficial gastritis (SG). PGC protein expression in gastric mucosa was measured by immunohistochemistry. The serum PGC level was determined by enzyme-linked immunosorbent assay (ELISA).
Results: In accordance with the following order SG-->GEU-->GA-->GC, the frequency of PGC homozygous allele 1 was gradually increased, which was higher in GC than in SG (P=0.018); while the protein expression of PGC in gastric mucosa was gradually decreased (P<0.01), along with a gradual decrease in the strong positive rate of PGC (P<0.05) except for SG vs. GEU. The serum level of PGC was significantly lower in SG than in GU(P=0.000) and GC(P=0.000). The frequency of PGC homozygous allele 1 was negatively correlated to PGC protein expression in gastric mucosa (r=-0.1085, P=0.023). From homozygous allele 1 to heterozygous allele 1, and to other genotypes, the PGC positive rate was gradually increased in gastric mucosa, with significant differences between homozygous allele 1 and other genotypes (P=0.009); while the strong-positive rate of PGC was gradually decreased only in SG group (P=0.047).
Conclusion: PGC gene insertion/deletion polymorphism is negatively related to PGC protein expression in gastric mucosa, but is not related to the serum PGC level.