Yu Xiaobo, Wei Bajin, Dai Yifan, Zhang Min, Wu Jian, Xu Xiao, Jiang Guoping, Zheng Shusen, Zhou Lin
Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
PLoS One. 2014 Apr 30;9(4):e94426. doi: 10.1371/journal.pone.0094426. eCollection 2014.
Although liver transplantation is one of the most efficient curative therapies of end stage liver diseases, recipients may suffer liver graft loss opst-operation. IRF-5, a member of Interferon Regulatory Factors, functions as a key regulator in TLR4 cascade, and is capable of inducing inflammatory cytokines. Although TLR4 has been proved to contribute to acute allograft rejection, including after liver transplantation, the correlation between IRF5 gene and acute rejection has not been elucidated yet.
The study enrolled a total of 289 recipients, including 39 females and 250 males, and 39 recipients developed acute allograft rejection within 6 months post-transplantation. The allograft rejections were diagnosed by liver biopsies. Genome DNA of recipients was extracted from pre-operative peripheral blood. Genotyping of IRF-5, including rs3757385, rs752637 and rs11761199, was performed, followed by SNP frequency and Hardy-Weinberg equilibrium analysis.
The genetic polymorphism of rs3757385 was found associated with acute rejection. G/G homozygous individuals were at higher risk of acute rejection, with a P value of 0.042 (OR = 2.34 (1.07-5.10)).
IRF5, which transcriptionally activates inflammatory cytokines, is genetically associated with acute rejection and might function as a risk factor for acute rejection of liver transplantations.
尽管肝移植是终末期肝病最有效的治疗方法之一，但受者术后可能会出现肝移植失败。干扰素调节因子（IRF）-5是干扰素调节因子家族的一员，在Toll样受体4（TLR4）信号通路中起关键调节作用，能够诱导炎性细胞因子。尽管TLR4已被证明与急性移植排斥反应有关，包括肝移植后，但IRF5基因与急性排斥反应之间的相关性尚未阐明。
本研究共纳入289例受者，其中女性39例，男性250例，39例受者在移植后6个月内发生急性移植排斥反应。通过肝活检诊断移植排斥反应。从术前外周血中提取受者的基因组DNA。对IRF-5进行基因分型，包括rs3757385、rs752637和rs11761199，随后进行单核苷酸多态性（SNP）频率和哈迪-温伯格平衡分析。
发现rs3757385的基因多态性与急性排斥反应有关。G/G纯合个体发生急性排斥反应的风险较高，P值为0.042（比值比[OR]=2.34[1.07-5.10]）。
转录激活炎性细胞因子的IRF5在基因上与急性排斥反应有关，可能是肝移植急性排斥反应的一个危险因素。
