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移植肾受者细胞因子基因多态性与表达水平及其与移植物功能的联合分析。

Combined analysis of cytokine gene polymorphism and the level of expression with allograft function in kidney transplant recipients.

机构信息

Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Autoimmune Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Transpl Immunol. 2014 Jan;30(1):46-51. doi: 10.1016/j.trim.2013.09.006. Epub 2013 Nov 6.

Abstract

Cytokines are important factors determining the outcome of transplantation since host ability in cytokine production may be affected by cytokine gene polymorphisms. The aim of the present study was to investigate the effect of IL-17, IL-23R and IL-21 gene polymorphisms in the outcome of kidney transplantation. A total of 250 kidney transplant recipients were included in this study. Overall 70 recipients (28%) experienced an acute rejection. IL-17 197 A/G, IL-21+1472 G/T, IL-21 5250 C/T, and IL-23R C/T gene polymorphisms were evaluated by PCR-RFLP or ARMS-PCR methods. The serum levels of IL-17 and IL-21 were also checked by ELISA. IL-17 GG carriers and G allele were significantly more frequent in patients with acute rejection as compared to patients without any sign of rejection (P=0.045 and P=0.032, respectively). In addition after gender classification, IL-23R AA carriers and A allele were significantly more frequent in male patients who experienced an acute rejection as compared to non-rejected patients (P=0.03, P=0.011, respectively). The IL-17 serum levels have also shown significant differences between rejected and non-rejected groups (24.37±32.94 for AR and 8.6±9.9 for non-AR groups, respectively; P=0.035). The mentioned results indicate that IL-17GG genotype, G allele and its serum level have predictive values for acute rejection. GG genotype and G allele of IL-17 is a genetic risk factor for development of acute rejection. Also, AA genotype and A allele of IL-23R is a sex dependent genetic risk factor for the development of acute rejection, but this subject needs to be studied in a different population.

摘要

细胞因子是决定移植结局的重要因素,因为宿主产生细胞因子的能力可能受到细胞因子基因多态性的影响。本研究旨在探讨白细胞介素-17(IL-17)、白细胞介素-23 受体(IL-23R)和白细胞介素-21 基因多态性对肾移植结局的影响。本研究共纳入 250 例肾移植受者。共有 70 例(28%)受者发生急性排斥反应。采用 PCR-RFLP 或 ARMS-PCR 方法检测 IL-17 197A/G、IL-21+1472G/T、IL-215250C/T 和 IL-23RC/T 基因多态性。采用 ELISA 法检测血清 IL-17 和 IL-21 水平。与无排斥反应的患者相比,急性排斥反应患者的 IL-17 GG 携带者和 G 等位基因更为常见(P=0.045 和 P=0.032)。此外,在性别分类后,与未发生排斥反应的患者相比,急性排斥反应男性患者的 IL-23RAA 携带者和 A 等位基因更为常见(P=0.03,P=0.011)。与未发生排斥反应的患者相比,急性排斥反应患者的血清 IL-17 水平也存在显著差异(AR 组为 24.37±32.94,非 AR 组为 8.6±9.9,P=0.035)。上述结果表明,IL-17GG 基因型、G 等位基因及其血清水平对急性排斥反应具有预测价值。IL-17GG 基因型和 G 等位基因是急性排斥反应发生的遗传危险因素。此外,IL-23RAA 基因型和 A 等位基因是急性排斥反应发生的性别依赖性遗传危险因素,但这一问题需要在不同人群中进一步研究。

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