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FOXP3 基因变异影响肾移植患者移植物的存活。

Genetic variants of FOXP3 influence graft survival in kidney transplant patients.

机构信息

Department of Internal Medicine, Transplantation Laboratory, Erasmus University Medical Center, Rotterdam, The Netherlands.

出版信息

Hum Immunol. 2013 Jun;74(6):751-7. doi: 10.1016/j.humimm.2013.02.008. Epub 2013 Feb 28.

Abstract

FOXP3(+) regulatory T cells (Treg) play a role in controlling alloreactivity. It has been shown that short (GT)n dinucleotide repeats (≤(GT)15; S) in the promoter region of the FOXP3 gene enhance the promoter activity when compared to long (GT)n repeats (≥(GT)16; L). The present study retrospectively investigated the influence of this (GT)n FOXP3 gene polymorphism on renal allograft survival. A total of 599 consecutive first-time kidney transplant patients (median follow-up time 7.7 years) were subdivided according to their FOXP3 genotype into the S-genotype group (SG) and the L-genotype group (LG). The SG was superior to the LG in both general graft survival censored for death (logrank test, p=0.013) and graft survival following acute rejection (p=0.021). Multivariate analysis defined the (GT)n FOXP3 dinucleotide repeat polymorphism as an independent factor and confirmed an advantage for the SG in renal allograft survival (HR=0.67, 95% CI 0.48-0.94, p=0.02). This gene association study identified a beneficial effect of FOXP3 genetic variants on graft survival in kidney transplant patients.

摘要

FOXP3(+)调节性 T 细胞 (Treg) 在控制同种异体反应中发挥作用。已经表明,FOXP3 基因启动子区域中的短 (GT)n 二核苷酸重复序列 (≤(GT)15; S) 与长 (GT)n 重复序列 (≥(GT)16; L) 相比,增强了启动子活性。本研究回顾性调查了这种 (GT)n FOXP3 基因多态性对肾移植存活的影响。将 599 例连续首次接受肾移植的患者(中位随访时间 7.7 年)根据 FOXP3 基因型分为 S 基因型组 (SG) 和 L 基因型组 (LG)。SG 在排除死亡的一般移植物存活率 (对数秩检验,p=0.013) 和急性排斥后移植物存活率 (p=0.021) 方面均优于 LG。多变量分析将 (GT)n FOXP3 二核苷酸重复多态性定义为独立因素,并证实 SG 在肾移植存活率方面具有优势 (HR=0.67,95%CI 0.48-0.94,p=0.02)。这项基因关联研究确定了 FOXP3 遗传变异对肾移植患者移植物存活的有益影响。

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