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[CTLA-4基因多态性与膀胱尿路上皮癌患者遗传易感性及预后的相关性]

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

作者信息

Li Junpeng, Zhang Lin, Xie Haifeng, Ge Yukun, Wang Lei

机构信息

Department of Urology, Xinxiang Central Hospital, Xinxiang, Henan 453000, China.

出版信息

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2024 Aug 10;41(8):988-993. doi: 10.3760/cma.j.cn511374-20240118-00053.

Abstract

OBJECTIVE

To assess the association of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene polymorphisms with the prognosis of patients with Bladder urothelial carcinoma (BUC).

METHODS

From 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.

RESULTS

No 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).

CONCLUSION

The 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.

摘要

目的

评估细胞毒性T淋巴细胞相关抗原4(CTLA-4)基因多态性与膀胱尿路上皮癌(BUC)患者预后的相关性。

方法

选取2019年2月至2020年10月在新乡市中心医院接受治疗的256例BUC患者作为研究组,同时选取250例健康个体作为对照组。采用聚合酶链反应-限制性片段长度多态性分析方法测定rs5742909(-318C/T)、rs231775(+49A/G)和rs4553808(-1661A/G)的基因型。比较两组CTLA-4基因的基因型和等位基因频率。所有患者均接受了手术治疗,并进行了3年的随访,根据疾病状况分为预后良好组(n = 166)和预后不良组(n = 86)。比较等位基因和基因型的分布,并采用Kaplan-Meier分析评估基因多态性与预后的相关性。

结果

两组在性别、年龄、BMI、吸烟史和饮酒方面无显著差异(P > 0.05)。与对照组相比,研究组中rs231775(+49A/G)和rs4553808(-1661A/G)位点的GG基因型和G等位基因频率显著更高(P < 0.05),而两组间rs5742909位点的基因型和等位基因频率无统计学差异(P > 0.05)。在完成随访的252例受试者中,86例预后不良,166例预后良好。与预后不良组相比,预后良好组中rs231775(+49A/G)和rs4553808(-1661A/G)位点的GG基因型和G等位基因频率显著更低(P < 0.05)。Kaplan-Meier生存曲线分析显示,rs231775(+49A/G)和rs4553808(-1661A/G)位点GG基因型患者的生存时间显著短于AA或AG基因型患者(Log Rank 2 = 13.654,9.974,P < 0.001)。

结论

CTLA-4基因的rs231775和rs4553808位点多态性与BUC的遗传易感性和预后不良相关,较高的GG基因型频率可能增加患者感染风险和预后不良。

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