Impact of Polymorphisms of TLR4/CD14 and TLR3 on Acute Rejection in Kidney Transplantation
Impact of Polymorphisms of TLR4/CD14 and TLR3 on Acute Rejection in Kidney Transplantation
复制标题
DOI：
10.1097/tp.0b013e3181b2f34a
复制
发表时间：
2009-09-15
期刊：
影响因子：
6.2
通讯作者：
Ahn, Curie
中科院分区：
文献类型：
--
作者：
Hwang, Young-Hwan;Ro, Han;Ahn, Curie
背景器官移植本身不可避免地通过Toll样受体（TLR）激活先天免疫系统，可能导致同种异体移植排斥和移植失败。我们评估了TLR 4/CD 14和TLR 3多态性与活体肾移植后急性排斥反应的可能关系。使用1996年1月至2006年7月期间216对成人活体供肾移植的供受体DNA样本对TLR 4 - 1607 T/C（rs 10759932）、-2026 A/G（rs 1927914）、CD 14 - 159 C/T（rs 2569190）和TLR 3 rs3775290、rs3775291和rs3775296进行基因分型。采用双荧光素酶报告基因分析方法，检测TLR 4基因启动子区单核苷酸多态性（SNPs）的功能意义。216例成人肾移植患者中，42例（19.4%）在1年内发生急性排斥反应。受体和供体TLR 4 rs 10759932的基因型分布在对照组（无排斥）和急性排斥组之间差异显著。对于受体rs 10759932，TC+CC基因型相对于TT基因型的调整优势比为0.25（95%置信区间，0.11-0.57; P=0.001）。当受体或供体中存在rs 10759932 CC基因型时，未发生急性排斥反应（Fisher精确检验，P=0.023）。rs 10759932 C等位基因的存在与较高的无排斥生存率相关（对数秩检验，P=0.0053）。然而，野生型和变体TLR 4启动子之间的转录活性没有差异。与TLR 4相比，TLR 3和CD 14的单核苷酸多态性对急性排斥反应无影响。这些结果表明TLR 4在肾移植急性排斥反应的发病机制中的重要性。
Background. Organ transplantation itself inevitably activates the innate immune system by toll-like receptors (TLRs), potentially leading to allograft rejection and graft failure. We evaluated the possible association between the TLR4/CD14 and TLR3 polymorphisms of donor-recipient pairs, and acute rejection after living donor kidney transplantation.Methods. TLR4 - 1607T/C (rs10759932), -2026A/G (rs1927914); CD14-159C/T (rs2569190); and TLR3 rs3775290, rs3775291, and rs3775296 were genotyped using DNA samples from 216 donor-recipient pairs of adult living donor kidney transplantation between January 1996 and July 2006. Dual luciferase reporter assay was performed to determine the functional significance of promoter single-nucleotide polymorphisms (SNPs) of TLR4.Results. Acute rejection occurred in 42 recipients (19.4%) of 216 adult transplant patients within I year. The genotype distributions of both recipient and donor TLR4 rs10759932 differed significantly between the control (no rejection) and acute rejection groups. For recipient rs10759932, the adjusted odds ratio for the TC+CC over TT genotype was 0.25 (95% confidence interval, 0.11-0.57; P=0.001). When the rs10759932 CC genotype was present in the recipient or donor, no episode of acute rejection occurred (Fisher's exact test, P=0.023). The presence of the rs10759932 C allele was associated with higher rejection-free survival rates (log-rank test, P=0.0053). However, there was no difference in transcriptional activity between wild-type and variant promoters of TLR4. In contrast to TLR4, SNPs of TLR3 or CD14 had no influence on acute rejection.Conclusion. These findings suggest the importance of TLR4 in the pathogenesis of acute rejection in kidney transplantation.