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白细胞介素17A和白细胞介素17F基因多态性对肾移植后长期肾移植功能及恢复透析的影响。

Influence of the IL17A and IL17F gene polymorphisms on the long-term kidney allograft function and return to dialysis after kidney transplantation.

作者信息

Romanowski Maciej, Kłoda Karolina, Osękowska Bogumiła, Domański Leszek, Pawlik Andrzej, Safranow Krzysztof, Ciechanowski Kazimierz

机构信息

Clinical Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Szczecin, Poland.

Department of Physiology, Pomeranian Medical University, Szczecin, Poland.

出版信息

Clin Transplant. 2015 Dec;29(12):1187-94. doi: 10.1111/ctr.12649. Epub 2015 Nov 3.

Abstract

The immune response after allogenic transplantation is a complex phenomenon involving cytokines, chemokines, and other mediators of inflammation. The aim of this study was to evaluate the influence of the IL17A and IL17F gene polymorphisms on long-term kidney allograft function, graft function loss/return to dialysis, and mortality after kidney transplantation. This study enrolled 269 Caucasian deceased donor renal transplant recipients. The rs2275913:G>A (-197G>A) polymorphism within the IL17A gene promoter and rs2397084:T>C (Glu126Gly), rs11465553:G>A (Val155Ile), and rs763780:T>C (His167Arg) polymorphisms within the IL17F gene were genotyped. Creatinine concentrations 12, 24, 36, 48, and 60 months after transplantation were significantly higher in recipients with the rs2275913:A>G IL17A GG genotype (GG vs. GA + AA: p = 0.03, p = 0.004, p = 0.006, p = 0.03, p = 0.04, respectively). Moreover, the GG genotype was statistically significantly associated with increased risk of delayed graft function. This association remained significant in multivariate regression analysis adjusted for recipients' age and sex. In the case of the rs11465553, IL17F univariate Cox regression analysis showed statistically significant association of GA genotype with higher risk of graft loss/return to dialysis (GA vs. GG: HR = 2.795, 95%CI = 1.031-7.579, p = 0.04). The results of our study suggest that the GG genotype of the rs2275913 IL17A gene promoter polymorphism is associated with significantly impaired long-term kidney allograft function, whereas the GA genotype of the rs11465553 IL17F gene polymorphism may be associated with a significantly higher risk of graft function loss and return to dialysis after kidney transplantation.

摘要

同种异体移植后的免疫反应是一种复杂的现象,涉及细胞因子、趋化因子和其他炎症介质。本研究的目的是评估白细胞介素17A(IL17A)和白细胞介素17F(IL17F)基因多态性对肾移植长期功能、移植功能丧失/恢复透析以及肾移植后死亡率的影响。本研究纳入了269名白种人已故供体肾移植受者。对IL17A基因启动子内的rs2275913:G>A(-197G>A)多态性以及IL17F基因内的rs2397084:T>C(Glu126Gly)、rs11465553:G>A(Val155Ile)和rs763780:T>C(His167Arg)多态性进行基因分型。移植后12、24、36、48和60个月时,rs2275913:A>G IL17A GG基因型受者的肌酐浓度显著更高(GG与GA + AA相比:p分别为0.03、0.004、0.006、0.03、0.04)。此外,GG基因型与移植肾功能延迟恢复的风险增加在统计学上显著相关。在根据受者年龄和性别进行调整的多变量回归分析中,这种关联仍然显著。就rs11465553而言,IL17F单变量Cox回归分析显示,GA基因型与移植肾丧失/恢复透析的较高风险在统计学上显著相关(GA与GG相比:风险比[HR]=2.795,95%置信区间[CI]=1.031 - 7.579,p = 0.04)。我们的研究结果表明,rs2275913 IL17A基因启动子多态性的GG基因型与长期肾移植功能显著受损相关,而rs11465553 IL17F基因多态性的GA基因型可能与肾移植后移植肾功能丧失和恢复透析的显著更高风险相关。

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