Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Mol Biol Rep. 2011 Oct;38(7):4437-43. doi: 10.1007/s11033-010-0572-6. Epub 2010 Dec 4.
Liver transplantation is one of the most important therapies for end-stage liver diseases and is associated with major problems including infections and acute rejection. The outcome of transplantation can be determined by immune responses as a key role in response to the graft. Inflammatory and anti-inflammatory mediators especially cytokines influence the graft microenvironment. Th1 and Th2 immune responses in contrast to regulatory responses cause acute rejection or help graft survival. In this study, we evaluated the gene polymorphisms of IL-6 G-174C, TGF-β T + 869C, IL-4 C-590T, and IFN-γ T + 874A cytokines in liver transplant patients. ARMS-PCR method was used to characterize IL-6 G-174C, TGF-β T + 869C and IFN-γ T + 874A polymorphisms and PCR-RFLP using AvaII restriction enzyme was done for IL-4 C-590T characterization in 70 liver transplant patients. Acute rejection episodes were diagnosed according to standard criteria. The analysis of the results showed that IL-6-174 GG genotype ( P = 0.009, OR = 4.333, 95% CI = 1.043-18.000), IL-6-174G allele (P = 0.011, OR = 5.273, 95% CI = 1.454-19.127) was more frequent and IFN-γ +874 TT genotype was less frequent (P = 0.043, OR = 0.143, 95% CI = 0.0118-1.190) in acute rejection than in non-rejection patients. TGF-β T + 869C and IL-4 C-590T frequencies were not significantly different (P > 0.05). According to the results, it can be conclude that IL-6 G-174C and IFN-γ T + 874A gene polymorphisms have predictive values for acute rejection after liver transplantation. High producer genotype of IL-6 is a genetic risk factor and IFN-γ is a protective factor for acute rejection development.
肝移植是治疗终末期肝病的最重要疗法之一，与包括感染和急性排斥反应在内的重大问题相关。移植的结果可以通过免疫反应来确定，因为免疫反应在对移植物的反应中起着关键作用。炎症和抗炎介质，特别是细胞因子，影响移植物的微环境。Th1 和 Th2 免疫反应与调节反应相反，导致急性排斥反应或有助于移植物存活。在这项研究中，我们评估了白细胞介素 6 G-174C、转化生长因子-β T+869C、白细胞介素 4 C-590T 和干扰素-γ T+874A 细胞因子在肝移植患者中的基因多态性。采用 ARMS-PCR 方法对白细胞介素 6 G-174C、转化生长因子-β T+869C 和干扰素-γ T+874A 多态性进行特征分析，采用 AvaII 限制性内切酶的 PCR-RFLP 法对白细胞介素 4 C-590T 进行特征分析，对 70 例肝移植患者进行分析。根据标准标准诊断急性排斥反应。结果分析表明，白细胞介素 6-174 GG 基因型（P=0.009，OR=4.333，95%CI=1.043-18.000）、白细胞介素 6-174G 等位基因（P=0.011，OR=5.273，95%CI=1.454-19.127）在急性排斥反应患者中更为常见，干扰素-γ+874 TT 基因型（P=0.043，OR=0.143，95%CI=0.0118-1.190）较少。转化生长因子-β T+869C 和白细胞介素 4 C-590T 的频率无显著差异（P>0.05）。根据结果可以得出结论，白细胞介素 6 G-174C 和干扰素-γ T+874A 基因多态性对肝移植后急性排斥反应有预测价值。高产生基因型的白细胞介素 6 是遗传风险因素，而干扰素-γ 是急性排斥反应发展的保护因素。
