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胃蛋白酶原C(PGC)基因插入/缺失多态性与胃黏膜及血清中PGC蛋白表达的相关性

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

作者信息

Sun Li-Ping, Gong Yue-Hua, Dong Nan-Nan, Wang Lan, Yuan Yuan

机构信息

Cancer Research Institute, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning, China.

出版信息

Ai Zheng. 2009 May;28(5):487-92.

PMID:19624876
Abstract

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.

摘要

背景与目的

人胃蛋白酶原C(PGC)是一种在胃黏膜中合成的天冬氨酸蛋白酶。已发现位于第7外显子和第8外显子之间的PGC基因插入/缺失多态性与胃癌(GC)易感性相关。本研究旨在探讨PGC多态性与胃黏膜及血清中PGC蛋白表达之间的关系。

方法

采用聚合酶链反应(PCR)评估PGC插入/缺失多态性,随后对493例胃癌、萎缩性胃炎(AG)、胃糜烂溃疡(GEU)和浅表性胃炎(SG)患者进行直接DNA测序。采用免疫组织化学法检测胃黏膜中PGC蛋白表达。采用酶联免疫吸附测定(ELISA)法测定血清PGC水平。

结果

按照SG→GEU→AG→GC的顺序,PGC纯合子等位基因1的频率逐渐升高,在胃癌中高于浅表性胃炎(P = 0.018);而胃黏膜中PGC蛋白表达逐渐降低(P < 0.01),PGC强阳性率除SG与GEU外也逐渐降低(P < 0.05)。浅表性胃炎患者血清PGC水平显著低于胃溃疡(P = 0.000)和胃癌患者(P = 0.000)。PGC纯合子等位基因1的频率与胃黏膜中PGC蛋白表达呈负相关(r = -0.1085,P = 0.023)。从纯合子等位基因1到杂合子等位基因1,再到其他基因型,胃黏膜中PGC阳性率逐渐升高,纯合子等位基因1与其他基因型之间存在显著差异(P = 0.009);而仅在浅表性胃炎组中PGC强阳性率逐渐降低(P = 0.047)。

结论

PGC基因插入/缺失多态性与胃黏膜中PGC蛋白表达呈负相关,但与血清PGC水平无关。

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