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受体和供体白细胞介素-10、肿瘤坏死因子α和干扰素γ基因分型对急性肾移植排斥反应发生率的影响。

Influence of recipient and donor IL-10, TNFA and INFG genotypes on the incidence of acute renal allograft rejection.

作者信息

Azarpira Negar, Aghdai Mahdokht H, Raisjalali Ghanbar A, Darai Masumeh, Tarahi Moham J

机构信息

Organ Transplant Research Center, Nemazi Hospital, Shiraz University of Medical Sciences, Zand Street, 7193711351, Shiraz, Iran.

出版信息

Mol Biol Rep. 2009 Jul;36(6):1621-6. doi: 10.1007/s11033-008-9361-x. Epub 2008 Sep 16.

Abstract

OBJECTIVE

Transplantation of renal grafts is an established treatment for renal failure in a variety of medical conditions. Acute allograft rejection remains an important cause of morbidity after kidney transplantation, and has been shown to be a crucial determinant of long-term graft function. Although rejection is mediated by recipient lymphocytes, both donor and recipient factors contribute to the local environment that influences the severity of rejection response. Because cytokines are the main components of immune responses, we evaluate single nucleotide polymorphisms (SNP) of several cytokine genes that may influence the production of a given cytokine and therefore the features of immune reactions.

MATERIAL AND METHODS

The aim of this study was to determine the impact of the cytokine gene polymorphism of pro and anti-inflammatory cytokines on the development of acute allograft rejection, which could be used in pretransplant patient assessment. Three SNPs including IL-10 (-1082 G/A), TNFA (-308 G/A), and INFG (+874 T/A) were analyzed in 46 patients with acute allograft rejection, 54 patients with stable graft function and their kidney donors by PCR-ARMS method.

RESULTS

We are unable to find statistically significant association between any of the studies polymorphisms and clinical outcomes.

CONCLUSION

We have found no evidence to suggest that either recipient or donor cytokines polymorphisms determine the incidence of acute rejection after renal transplantation. Our observation, however, is based on few cases, and this may mask a possible favorable effect. It is recommended that several functionally related genes should be tested in similar studies, since this approach has a higher chance to detect genetic risk factors than the screening of single genetic variants.

摘要

目的

肾移植是治疗多种医学病症所致肾衰竭的既定疗法。急性移植肾排斥反应仍是肾移植后发病的重要原因,且已被证明是长期移植肾功能的关键决定因素。尽管排斥反应由受体淋巴细胞介导,但供体和受体因素均会影响局部环境,进而影响排斥反应的严重程度。由于细胞因子是免疫反应的主要成分,我们评估了几种细胞因子基因的单核苷酸多态性(SNP),这些多态性可能影响特定细胞因子的产生,从而影响免疫反应的特征。

材料与方法

本研究旨在确定促炎和抗炎细胞因子基因多态性对急性移植肾排斥反应发生发展的影响,这可用于移植前患者评估。采用聚合酶链反应-扩增阻滞突变系统(PCR-ARMS)方法,对46例急性移植肾排斥反应患者、54例移植肾功能稳定的患者及其肾供体进行了白细胞介素-10(IL-10,-1082 G/A)、肿瘤坏死因子α(TNFA,-308 G/A)和干扰素γ(INFG,+874 T/A)3种单核苷酸多态性分析。

结果

我们未能发现任何研究的多态性与临床结果之间存在统计学显著关联。

结论

我们没有发现证据表明受体或供体细胞因子多态性决定肾移植后急性排斥反应的发生率。然而,我们的观察基于少数病例,这可能掩盖了可能存在的有利影响。建议在类似研究中检测几个功能相关基因,因为这种方法比筛选单个基因变异更有机会检测到遗传风险因素。

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