细胞程序性死亡-配体1基因启动子区rs10815225多态性与结直肠癌的关联研究

Association of rs10815225 polymorphism in the promoter region of programmed cell death ligand 1 gene with colorectal cancer

目的探讨位于细胞程序性死亡-配体1(PD-L1)基因启动子区的rs10815225多态性与结直肠癌的相关性。方法直接测序法分析215例结直肠癌患者和236例体检健康者rs10815225多态性,定量PCR检测65例结直肠癌组织中PD-L1 mRNA的表达变化。结果与GG基因型相比,CG基因型显著降低了结直肠癌的发病风险(OR=0.48,95%CI 0.28~0.83,P=0.01)。双荧光素酶报告基因结果显示,与rs10815225G等位基因相比,rs10815225C对应的荧光素酶活性显著降低(P<0.05)。基因型—表型结果显示,携带rs10815225CG基因型结直肠癌患者中PD-L1 mRNA表达明显低于GG基因型携带者(P<0.05)。结论PD-L1基因启动子区rs10815225CG基因型可能通过降低基因转录活性和PD-L1 mRNA表达,从而降低中国汉族人群结直肠癌的发病风险。

Objective To investigate the relationship between rs10815225 polymorphism in the promoter region of programmed cell death ligand 1(PD-L1)gene and colorectal cancer.Methods The rs10815225 polymorphism was analyzed in 215 colorectal cancer patients and 236 healthy people by direct sequencing,and the expression of PD-L1 mRNA in 65 colorectal cancer tissues was detected by quantitative PCR.Results Compared with GG genotype,CG genotype significantly reduced the risk of colorectal cancer(OR=0.48,95%CI 0.28-0.83,P=0.01).The results of double luciferase reporter gene showed that the luciferase activity of rs10815225c was significantly lower than that of rs10815225g(P<0.05).The results of genotype phenotype showed that the expression of PD-L1 mRNA in colorectal cancer patients with rs10815225cg genotype was significantly lower than that in patients with GG genotype(P<0.05).Conclusion The rs10815225CG genotype in the promoter region of PD-L1 gene may reduce the risk of colorectal cancer in Chinese Han population by reducing gene transcription activity and PD-L1 mRNA expression.