胃癌患者CTLA-4启动子及外显子区域基因多态性的研究

Polymorphism of CTLA-4 and Helicobacter pylori infection on gastric cancer genesis

目的:探讨细胞毒性T淋巴细胞相关抗原4(CTLA-4)基因外显子49位点及启动子1661位点单核苷酸多态性(SNP)、幽门螺杆菌(Hp)感染与青岛地区人群胃癌的发病率的关系。方法:采用聚合酶链反应-限制性片段长度多态分析(PCR-RFLP)检测来自青岛地区人群胃癌患者、萎缩性胃炎及对照组患者中位CTLA-4+49A/G及-1661A/G基因多态性的分布,Hp检测采用病理学诊断。结果:1)胃癌组外显子49位AG及GG基因型频率显著高于对照组(P均<0.05),携带AG及GG基因型者罹患胃癌的风险分别增加至2.63倍及5.69倍。启动子1661位AG+GG基因型频率显著高于对照组(P=0.01),携带AG+GG基因型的个体罹患胃癌的风险增加到2.63倍。2)CTLA-4+49A/G:与AA/Hp阴性者相比,AG/Hp阴性、GG/Hp阴性、AG/Hp阳性及GG/Hp阳性人群罹患胃癌的风险都显著增加,其中GG/Hp阳性者增加至9.56倍(P=0.000)。3)CTLA-4-1661A/G:以AA基因型并Hp阴性者为对照,AG+GG/Hp阴性、AA/Hp阳性、AG+GG/Hp阳性个体罹患胃癌的风险增加,其中AG+GG基因型并Hp阳性个体的患病风险显著增高,为对照组的4.04倍(P=0.008)。结论:CTAL-4+49A/G及-1661A/G基因多态性与胃癌的遗传易感性相关。

Objective： To analyze the relationship between extron 49 site and promoter 1661 in CTLA-4 gene polvmorphism and infection of Helicobacter in Qingdao area and susceptibility to gastric cancer genesis. Methods： Polymerase chain restriction fragment length polymorphism and direct sequencing were performed to analyze the genotype of the A/G polymorphism in 49 site and 1661 site region, and Hp was detected by pathological diagnosis. Results： 1）The frequency of AG and GG genotype in 49 site were higher in the gastric cancer group compared to the control group （P〈0.05）. The frequency of AG＋GG genotype in 1661 site was higher in the gastric cancer group compared to the control group（P=0.01 ）, moreover, individuals with the CTLA-4-1661AG＋GG genotype rose to 2.63 fold risk for gastric cancer. 2）in 49 site, Compared with CTLA-4 the AA genotype and the H. pylori negative individuals, there was an increased risk of developing gastric cancer for those carrying GG genotype and H. priori positive individuals ,with 9.56 fold risk. 3）In 1661 site, Compared with CTLA-4 the AA genotype and the H. pylori negative individuals,there was an increased risk of developing gastric cancer for those carrying AG＋GG genotype and H. pylori positive individuals, with 4.04 fold risk. Conclusion： There was a relationship between CTLA-4＋49 A/G and 1661 A/G polymorphism and susceptibility to gastric cancer.