骨桥蛋白基因多态性与胃癌易感性的关系

Relationship between osteopontin gene polymorphism and susceptibility to gastric cancer

目的探讨骨桥蛋白(OPN)基因多态性与胃癌易感性的相关性。方法采用聚合酶链式反应及基因测序的方法检测胃癌患者(200例)与健康对照者(200例)中OPN启动子(-66、-156、-443)的基因型分布。构建OPN-443位点野生型质粒以及突变型质粒,利用荧光素酶报告基因检测系统检测相对荧光强度。结果 OPN SNP-443 C/C突变型基因型在胃癌患者中Ⅳ期与Ⅰ(ⅠA+ⅠB)期、其他分期(ⅠA+ⅠB+Ⅱ+Ⅲ)间差异均有统计学意义(P<0.05),OPN SNP-443 T/C杂合子型基因型在Ⅳ期与其他分期(ⅠA+ⅠB+Ⅱ+Ⅲ)间差异有统计学意义(P<0.05)。与野生型报告基因质粒相比,胃癌MKN28细胞中突变型报告基因相对荧光素酶活性增加(P<0.05)。结论 OPN基因启动子区-433位点的变异可能与胃癌转移相关。

Objective To investigate the relationship between osteopontin（OPN） gene polymorphism and susceptibility to gastric cancer.Methods The distributions of OPN promoter（-66,-156,-443） genotypes in patients with gastric cancer（200 cases） and healthy people（200 cases） were detected by polymerase chain reaction restriction fragment length polymorphism and gene sequencing method.The wild-type and mutant plasmids of OPN-443 site were constructed and then the relative fluorescence intensity was measured by luciferase reporter gene assay.Results There was a significant difference in the mutant genotype of OPN SNP-443 C/C between stage Ⅳ and stage Ⅰ（ⅠA＋ⅠB）,other stage（ⅠA＋ⅠB＋Ⅱ＋Ⅲ） in patients with gastric cancer（P〈0.05）.And the heterozygote genotype of OPN SNP-443 T/C in stage Ⅳ was obviously different from that in other stage（ⅠA＋ⅠB＋Ⅱ＋Ⅲ）（P〈0.05）.Compared with wild-type plasmid,the relative luciferase activation of mutant report gene was increased in gastric cancer MKN28 cells（P〈0.05）.Conclusion The variation of OPN promoter region at 443 site may be associated with the metastasis of gastric cancer.