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细胞因子基因多态性对肾移植长期预后的影响。

Influence of cytokine genes polymorphisms on long-term outcome in renal transplantation.

作者信息

Breulmann Bärbel, Bantis Christos, Siekierka Magdalena, Blume Cornelia, Aker Sendogan, Kuhr Nicola, Grabensee Bernd, Ivens Katrin

机构信息

Department of Nephrology, Heinrich-Heine-University, Düsseldorf, Germany.

出版信息

Clin Transplant. 2007 Sep-Oct;21(5):615-21. doi: 10.1111/j.1399-0012.2007.00697.x.

DOI:10.1111/j.1399-0012.2007.00697.x
PMID:17845635
Abstract

BACKGROUND

Recently, polymorphisms of cytokine genes have been associated with modified gene expression and increased cytokine production. We evaluated the influence of interleukin-10 (IL-10) gene G-1082A, tumour necrosis factor alpha (TNFalpha) gene G-308A and IL-6 gene G-174C polymorphisms on the rejection rate, renal function and long-term outcome in renal transplantation.

PATIENTS AND METHODS

We studied n = 224 consecutive patients, who underwent renal transplantation at our centre from 1998 to 2001 (cadaveric: n = 175, living related: n = 49) followed up for 4.9 +/- 2.0 yr and n = 100 healthy volunteers. IL-10 gene G-1082A, TNFalpha gene G-308A and IL-6 gene G-174C polymorphisms were determined by polymerase chain reaction (PCR) amplification.

RESULTS

The genotype distribution of the investigated polymorphisms was similar in patients and controls (ns). The age of donor and the recipient, the number of HLA mismatches and cold and warm ischemic time did not differ among patients with different genotypes (ns). No association between cytokine polymorphisms and the incidence of acute rejection episodes was detected (ns). The cytokine genotypes did not correlate with serum creatinine or creatinine clearance at any time during follow up (ns). Furthermore, there was no significant difference in the genotype frequencies among patients experiencing graft failure (ns). Patients with different cytokine gene polymorphisms showed similar outcomes in the Kaplan-Meier analysis of graft survival (ns). Finally, cytokine polymorphisms had no influence on the acute rejection rate or graft outcome also in the subgroup of HLA-DR mismatched grafts (ns).

CONCLUSION

Our results suggest that IL-10 gene G-1082A, TNFalpha gene G-308A and IL-6 gene G-174C polymorphisms are no major risk factors in renal transplantation.

摘要

背景

最近,细胞因子基因多态性与基因表达改变及细胞因子产生增加有关。我们评估了白细胞介素-10(IL-10)基因G-1082A、肿瘤坏死因子α(TNFα)基因G-308A和IL-6基因G-174C多态性对肾移植排斥率、肾功能及长期预后的影响。

患者与方法

我们研究了1998年至2001年在本中心接受肾移植的连续224例患者(尸体肾移植:175例,亲属活体肾移植:49例),随访4.9±2.0年,并纳入100名健康志愿者。通过聚合酶链反应(PCR)扩增来确定IL-10基因G-1082A、TNFα基因G-308A和IL-6基因G-174C多态性。

结果

患者和对照组中所研究多态性的基因型分布相似(无统计学差异)。不同基因型患者的供体和受体年龄、HLA错配数以及冷、热缺血时间无差异(无统计学差异)。未检测到细胞因子多态性与急性排斥反应发生率之间存在关联(无统计学差异)。在随访期间的任何时间,细胞因子基因型与血清肌酐或肌酐清除率均无相关性(无统计学差异)。此外,移植失败患者的基因型频率无显著差异(无统计学差异)。在移植存活的Kaplan-Meier分析中,不同细胞因子基因多态性的患者显示出相似的预后(无统计学差异)。最后,在HLA-DR错配移植亚组中,细胞因子多态性对急性排斥率或移植预后也无影响(无统计学差异)。

结论

我们的结果表明,IL-10基因G-1082A、TNFα基因G-308A和IL-6基因G-174C多态性不是肾移植的主要危险因素。

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