Citores M J, Baños I, Noblejas A, Rosado S, Castejon R, Cuervas-Mons V
Laboratorio de Medicina Interna, Servicio de Medicina Interna, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain.
Transplant Proc. 2011 Jul-Aug;43(6):2224-6. doi: 10.1016/j.transproceed.2011.05.011.
Liver transplantation activates the innate immune system by toll-like receptors (TLRs), potentially leading to allograft rejection and graft failure. The aim of this study was to evaluate the possible association of different single nucleotide polymorphisms (SNPs) in several TLR genes with the incidence of acute graft rejection in liver transplant recipients for hepatitis C virus (HCV)-related cirrhosis. This is a single-center study of 100 adult patients who received a first whole only liver graft from deceased donors at our institution between 1988 and 2009 for cirrhosis due to HCV infection. We examined 10 SNPs in the TLR1 (S6021), TLR2 (R753Q), TLR3 (L412F), TLR4 (D299G and T399I), TLR5 (R392X), TLR6 (S249P), TLR7 (Q11L), and TLR9 (-1237T/C and -1486C/T) genes. Genotyping was carried out with the LightSNiP typing assay (TIB-MolBiol, Berlin, Germany) by analyzing the melting curves with the LightCycler 480 system (Roche Applied Science, Mannheim, Germany). Recipient allelic and genotypic distributions for each SNP were compared among patients with and without acute rejection within the first 3 months after transplantation. We found the homozygous mutant TT genotype for TLR3 L412F was associated with a lower rate of acute rejection when compared with the homozygous wild-type genotype [odds ratio (OR) = 0.1, 95% confidence interval (95% CI) = 0.01-0.86; P = .017], and showed a trend toward a lower graft rejection rate when compared with patients carrying one or two C alleles (OR = 0.15, 95% CI = 0.02-1.2, P = .05). No other associations with acute rejection rates were found for any other SNP evaluated. This preliminary study suggests an important role for SNP TLR3 L412F in acute rejection in liver transplant patients for HCV-related cirrhosis. Nevertheless, these findings must be prospectively validated in other cohorts of patients as well as in patients after liver transplantation for other etiologies than HCV.
肝移植通过Toll样受体（TLR）激活先天免疫系统，这可能导致同种异体移植排斥反应和移植失败。本研究的目的是评估几种TLR基因中不同单核苷酸多态性（SNP）与丙型肝炎病毒（HCV）相关肝硬化肝移植受者急性移植排斥反应发生率之间的可能关联。这是一项单中心研究，研究对象为100例成年患者，他们于1988年至2009年间在我们机构接受了首例来自已故供体的全肝移植，用于治疗因HCV感染导致的肝硬化。我们检测了TLR1（S6021）、TLR2（R753Q）、TLR3（L412F）、TLR4（D299G和T399I）、TLR5（R392X）、TLR6（S249P）、TLR7（Q11L）以及TLR9（-1237T/C和-1486C/T）基因中的10个SNP。使用LightSNiP分型检测法（德国柏林的TIB-MolBiol公司），通过罗氏应用科学公司（德国曼海姆）的LightCycler 480系统分析熔解曲线进行基因分型。比较移植后前3个月内发生和未发生急性排斥反应的患者中每个SNP的受体等位基因和基因型分布。我们发现，与纯合野生型基因型相比，TLR3 L412F的纯合突变TT基因型与较低的急性排斥反应发生率相关[比值比（OR）=0.1，95%置信区间（95%CI）=0.01-0.86；P=0.017]，并且与携带一个或两个C等位基因的患者相比，显示出较低的移植排斥反应率趋势（OR=0.15，95%CI=0.02-1.2，P=0.05）。对于评估的任何其他SNP，均未发现与急性排斥反应率有其他关联。这项初步研究表明，SNP TLR3 L412F在HCV相关肝硬化肝移植患者的急性排斥反应中起重要作用。然而，这些发现必须在其他患者队列以及非HCV病因的肝移植患者中进行前瞻性验证。
