Kocierz M, Siekiera U, Kolonko A, Karkoszka H, Chudek J, Cierpka L, Wiȩcek A
Department of Nephrology, Endocrinology and Metabolic Diseases, Medical University of Silesia, Katowice, Francuska, Poland.
Tissue Antigens. 2011 Apr;77(4):283-90. doi: 10.1111/j.1399-0039.2010.01623.x.
The influence of cytokine gene polymorphisms on transplanted kidney outcome is not well understood. The aim of this one-centre study was to analyse the association between tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-10, interferon-γ (IFN-γ) and transforming growth factor-β1 (TGF-β1) genotypes and the incidence of delayed graft function (DGF), acute rejection (AR) and 5-year kidney graft loss. Genotyping was performed in 199 subsequent kidney graft recipients from deceased donors without induction therapy based on polymerase chain reaction method using sequence-specific primers for TNF-α (-308A/G), IL-10 (-1082A/G, -819T/C and -592A/C), IL-6 (-174G/C), IFN-γ (+874T/A) and TGF-β1 (in codons 10T/C and 25G/C). Genotypes were grouped according to the strength of cytokine expression. During a 5-year follow-up period, 14 patients died with functioning graft and 33 developed graft failure. The analysed polymorphisms were not associated with the incidence of DGF. The frequency of early episodes of AR was significantly associated only with TGF-β1 genotype. There was an association between -174G/C IL-6 gene polymorphism and the death-censored kidney graft survival. The risk of graft loss during 5-year follow-up period was greater by 57% for GG or GC (higher IL-6 production) than for CC carriers. None of the other analysed polymorphisms significantly influenced both patients and kidney graft survival, also in the analysis of the subgroup with human leucocyte antigen-DR mismatch. -174G/C IL-6 genotype of the kidney graft recipient could modulate the rate of graft excretory function deterioration and the risk of graft loss by influencing their constitutional expression.
细胞因子基因多态性对移植肾预后的影响尚未完全明确。本单中心研究旨在分析肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、IL-10、干扰素-γ(IFN-γ)和转化生长因子-β1(TGF-β1)基因多态性与移植肾功能延迟恢复(DGF)、急性排斥反应(AR)发生率及5年移植肾失功之间的关联。对199例接受来自 deceased 供体肾移植且未接受诱导治疗的患者,采用基于聚合酶链反应的序列特异性引物法,对TNF-α(-308A/G)、IL-10(-1082A/G、-819T/C和-592A/C)、IL-6(-174G/C)、IFN-γ(+874T/A)和TGF-β1(密码子10T/C和25G/C)进行基因分型。根据细胞因子表达强度对基因型进行分组。在5年随访期内,14例患者移植肾功能正常时死亡,33例发生移植肾失功。分析的多态性与DGF发生率无关。AR早期发作频率仅与TGF-β1基因型显著相关。IL-6基因-174G/C多态性与死亡校正后的移植肾存活有关。在5年随访期内,GG或GC(IL-6产生较高)携带者移植肾失功风险比CC携带者高57%。在对人类白细胞抗原-DR错配亚组的分析中,其他分析的多态性均未对患者及移植肾存活产生显著影响。移植肾受体的IL-6基因-174G/C基因型可能通过影响其固有表达来调节移植肾排泄功能恶化速率及移植肾失功风险。