CTLA-4基因多态性与膀胱尿路上皮癌遗传易感性及预后的相关性分析

Association of CTLA-4 gene polymorphisms with the genetic susceptibility and prognosis of patients with Bladder urothelial carcinoma

目的探讨细胞毒性T淋巴细胞相关抗原-4(CTLA-4)基因的多态性与膀胱尿路上皮癌(BUC)患者预后之间的相关性。方法选取新乡市中心医院2019年2月至2020年10月收治的256例BUC患者作为研究组,另选同期250例健康体检者作为对照组,采用PCR-限制性片段长度多态法对rs5742909(-318C/T)、rs231775(+49A/G)、rs4553808(-1661A/G)位点进行基因分型,比较两组的一般资料、CTLA-4基因型、等位基因的分布情况。所有患者均接受手术治疗,术后随访3年,根据结果将患者分为预后良好组(n=166)和预后不良组(n=86),比较两组的等位基因以及基因型的分布,用Kaplan-Meier法分析CTLA-4基因多态性与患者预后的相关性。结果两组在性别、年龄、BMI、吸烟史、饮酒史方面的差异无统计学意义(P>0.05);研究组rs231775(+49A/G)和rs4553808(-1661A/G)位点GG基因型与G等位基因的频率均显著高于对照组(P<0.05),rs5742909位点的基因型和等位基因频率差异无统计学意义(P>0.05)。在252例完成随访者中,预后不良86例,良好166例,预后良好组CTLA-4基因rs231775(+49A/G)位点和rs4553808(-1661A/G)位点GG基因型以及G等位基因的频率显著低于预后不良组(P<0.05),Kaplan-Meier生存曲线分析显示rs231775(+49A/G)位点和rs4553808(-1661A/G)位点GG基因型患者生存期显著短于AA+AG基因型(Log Rank 2=13.654、9.974,P<0.001)。结论CTLA-4基因rs231775位点、rs4553808位点的多态性均与BUC的遗传易感性及不良预后相关,其GG基因型可能增加感染以及不良预后的风险。

ObjectiveTo assess the association of cytotoxic T lymphocyte-associated antigen-4(CTLA-4)gene polymorphisms with the prognosis of patients with Bladder urothelial carcinoma(BUC).MethodsFrom February 2019 to October 2020,256 BUS patients treated at the Xinxiang Central Hospital were selected as the study group,whilst 250 healthy individuals were selected as the control group.Genotypes of rs5742909(-318C/T),rs231775(+49A/G)and rs4553808(-1661A/G)were determined by PCR-restriction fragment length polymorphism assay.The frequencies of genotypes and alleles of the CTLA-4 gene were compared between the two groups.All patients had undergone surgical treatment and were followed up for 3 years and divided into good prognosis group(n=166)and poor prognosis group(n=86)based on the status of disease.The distribution of alleles and genotypes were compared,and Kaplan-Meier analysis was used to assess the association of genetic polymorphisms with the prognosis.ResultsNo significant difference was found in the gender,age,BMI,smoking history and alcohol use between the two groups(P>0.05).The frequencies of GG genotype and G allele for the rs231775(+49A/G)and rs4553808(-1661A/G)loci were significantly higher in the study group compared with the control group(P<0.05),whilst no statistical difference was found in the genotypic and allelic frequency for the rs5742909 locus between the two groups(P>0.05).Among the 252 subjects who had completed follow-up,86 had poor prognosis and 166 had good prognosis.The frequencies of GG genotype and G allele at the rs231775(+49A/G)and rs4553808(-1661A/G)loci were significantly lower in the good prognosis group compared with the poor prognosis group(P<0.05).Kaplan-Meier survival curve analysis showed that the survival time of patients with GG genotype for the rs231775(+49A/G)and rs4553808(-1661A/G)loci was significantly shorter than patients with AA or AG genotypes(Log Rank 2=13.654,9.974,P<0.001).ConclusionThe polymorphisms of the rs231775 and rs4553808 loci of the CTLA-4 gene are associated with genetic susceptibility and poor prognosis for BUC,and a higher GG genotypic frequency may increase the risk for infection and poor prognosis of the patients.