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研究白细胞介素-23 受体(IL-23R)、白细胞介素-17(IL-17)、白细胞介素-21(IL-21)多态性与伊朗肝移植受者急性移植物排斥反应及血清白细胞介素-17、白细胞介素-21 水平的关系。

Study of the relationships between IL-23R, IL-17, IL-21 polymorphisms and serum level of IL-17, IL-21 with acute graft rejection in iranian liver transplant recipients.

机构信息

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

出版信息

Immunol Invest. 2014;43(1):69-85. doi: 10.3109/08820139.2013.826240.

DOI:10.3109/08820139.2013.826240
PMID:24313807
Abstract

Cytokines are important factors determining the outcome of transplantation. Since host ability in cytokine production may be affected by cytokine genes polymorphisms, the aim of the present study was to investigate the effect of IL-17, IL-23R and IL-21 gene polymorphisms in outcome of liver transplantation. A total of 200 liver transplant recipients were included in this study. IL-17 -197 A/G, IL-21+1472 G/T, IL-21 5250 C/T, and IL-23R C/A polymorphisms were evaluated by PCR-RFLP or ARMS-PCR methods. The serum levels of IL-17 and IL-21 in rejected and non-rejected groups were determined by ELISA method. The results showed that IL-23R AC carriers and C allele were significantly more frequent in patients with acute rejection than patients without rejection (p=0.01 and p=0.0005, respectively). After gender classification, IL-23R AA and AC carriers were significantly more frequent in female patients (p=0.01, p=0.01, respectively) and IL-23R AA and AC carriers and A allele were significantly more frequent in male patients (p=0.009, p=0.02, p=0.003, respectively). There is a significant association between CC genotype and C alleles of IL-23R and AR in the patients receiving allograft from living donor (p=0.0003 and p=0.0008, respectively). Also, IL-23R AA and AC genotypes and C alleles showed a significant association with rejection in patients receiving allograft from cadaver donor (p=0.001, p=0.002 and p=0.02). The mentioned results indicate that IL-23R AC carriers and C allele have predictive values for acute rejection. AC genotype and C allele of IL-23R is a genetic risk factor for development of acute rejection. Also, AA and AC genotype of IL-23R is a sex dependent genetic risk factor for development of acute rejection. But this subject needs to be studied in different population.

摘要

细胞因子是决定移植结局的重要因素。由于宿主细胞因子产生能力可能受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(IL-21)基因多态性对肝移植结局的影响。本研究共纳入 200 例肝移植受者。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/A 多态性。采用 ELISA 法检测排斥和非排斥组患者血清中 IL-17 和 IL-21 的水平。结果显示,急性排斥组患者 IL-23RAC 携带者和 C 等位基因频率明显高于无排斥组(p=0.01 和 p=0.0005)。经性别分类后,女性患者 IL-23RAA 和 AC 携带者频率明显高于无排斥组(p=0.01、p=0.01),男性患者 IL-23RAA 和 AC 携带者及 C 等位基因频率明显高于无排斥组(p=0.009、p=0.02、p=0.003)。活体供体移植患者中,CC 基因型和 IL-23RC 等位基因与 AR 显著相关(p=0.0003 和 p=0.0008)。此外,尸肾移植患者中,IL-23RAA 和 AC 基因型及 C 等位基因与排斥反应显著相关(p=0.001、p=0.002 和 p=0.02)。上述结果表明,IL-23RAC 携带者和 C 等位基因对急性排斥反应有预测价值。IL-23RAC 基因型和 C 等位基因是急性排斥反应发生的遗传危险因素。此外,IL-23RAA 和 AC 基因型是急性排斥反应发生的性别依赖性遗传危险因素。但这一课题需要在不同人群中进一步研究。

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