Lu Kim C, Jaramillo Andrés, Lecha Rachel L, Schuessler Richard B, Aloush Aviva, Trulock Elbert P, Mendeloff Eric N, Huddleston Charles B, Alexander Patterson G, Mohanakumar T
Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Transplantation. 2002 Nov 15;74(9):1297-302. doi: 10.1097/00007890-200211150-00017.
A number of genetic polymorphisms have been shown to regulate the production and secretion of tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, interferon (IFN)-gamma, interleukin (IL)-6, and IL-10. Several of these genetic polymorphisms have been shown to be associated with either acute or chronic rejection of kidney, liver, and heart allografts and with development of allograft fibrosis after lung transplantation. The aim of this study was to assess the effect of these genetic polymorphisms on the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation.
Genetic polymorphisms were detected by means of polymerase chain reaction in 93 lung allograft recipients for functional polymorphisms in the TNF-alpha (-308), TGF-beta1 (+869 and +915), IL-6 (-174), IFN-gamma (+874), and IL-10 (-1082, -819, and -592) genes. Then, a correlation between BOS development and the presence of these cytokine genotypes was determined using Kaplan-Meier actuarial analysis.
A significant correlation was detected between the presence of high-expression polymorphisms of the IL-6 and IFN-gamma genes and BOS development after lung transplantation (P =0.045 and 0.039, respectively). Also, patients with high-expression polymorphisms in both genes developed BOS significantly earlier than patients with low-expression polymorphisms in one or both genes, suggesting a synergistic effect of the alleles during BOS pathogenesis (P =0.016). No correlation was detected between polymorphisms of the TNF-alpha, TGF-beta1, and IL-10 genes and development of BOS after lung transplantation.
The presence of high-expression polymorphisms at position -174 of the IL-6 gene and position +874 of the IFN-gamma gene significantly increases the risk for BOS development after lung transplantation.
多项基因多态性已被证实可调节肿瘤坏死因子（TNF）-α、转化生长因子（TGF）-β1、干扰素（IFN）-γ、白细胞介素（IL）-6和IL-10的产生与分泌。其中一些基因多态性已被证明与肾、肝和心脏同种异体移植的急性或慢性排斥反应以及肺移植后同种异体移植纤维化的发生有关。本研究的目的是评估这些基因多态性对肺移植后闭塞性细支气管炎综合征（BOS）发生的影响。
采用聚合酶链反应检测93例肺移植受者TNF-α（-308）、TGF-β1（+869和+915）、IL-6（-174）、IFN-γ（+874）和IL-10（-1082、-819和-592）基因的功能多态性。然后，使用Kaplan-Meier精算分析确定BOS发生与这些细胞因子基因型存在之间的相关性。
检测到IL-6和IFN-γ基因的高表达多态性与肺移植后BOS发生之间存在显著相关性（分别为P =0.045和0.039）。此外，两个基因均具有高表达多态性的患者发生BOS的时间明显早于一个或两个基因具有低表达多态性的患者，提示等位基因在BOS发病机制中具有协同作用（P =0.016）。未检测到TNF-α、TGF-β1和IL-10基因多态性与肺移植后BOS发生之间的相关性。
IL-6基因-174位点和IFN-γ基因+874位点存在高表达多态性显著增加肺移植后发生BOS的风险。
