PGC基因插入/缺失多态对胃粘膜及血清PGC蛋白表达的影响

Correlation of pepsinogen C (PGC) gene insertion / deletion polymorphism to PGC protein expression in gastric mucosa and serum

背景与目的:胃蛋白酶原C(pepsinogen C,PGC)是胃粘膜特异性功能酶的前体,PGC基因插入/缺失多态与胃癌易感性相关。本研究旨在探讨PGC基因多态与PGC蛋白表达的关系。方法:常规酚-氯仿法提取浅表性胃炎(superficial gastritis,SG)、胃糜烂溃疡(gastric ulcer,GEU)、萎缩性胃炎(atrophic gastritis,AG)及胃癌(gastric cancer,GC)患者共493例血凝块基因组DNA。PCR法扩增PGC基因7～8外显子间的100bp插入/缺失片段,检测PGC基因多态型,多态片段用测序证实。免疫组织化学方法检测胃粘膜PGC蛋白表达水平。ELISA法检测血清PGC蛋白含量。结果:从SG→GEU→GA→GC:PGC等位基因1纯合型分布频率逐渐升高,GC组显著高于SG组(P=0.018);胃粘膜PGC蛋白阳性率依次显著降低(均P<0.01),强阳性率逐渐降低,除SG组与GEU组外,其余各组间差异均有统计学意义(P<0.05);血清PGC蛋白含量GEU组和GC组显著高于SG组(P=0.000,P=0.000)。PGC基因1纯合型与胃粘膜PGC蛋白表达强度呈负相关(r=-0.1085,P=0.023),与PGC血清含量无相关性(P=0.435)。从等位基因1纯合型→等位基因1杂合型→其它型:PGC阳性率逐渐升高,等位基因1纯合型组与其它型之间的差异有统计学意义(P=0.009);SG组PGC等位基因1纯合型的PGC强阳性率低于其它型组(P=0.047)。结论:PGC基因多态与胃粘膜PGC蛋白表达呈负相关,与血清PGC含量无相关性。

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 immunohistochemitry. 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.