Seoul National University Kidney Research Institute, Seoul, Korea.
PLoS One. 2011 Feb 3;6(2):e16710. doi: 10.1371/journal.pone.0016710.
Genetic interaction between donor and recipient may dictate the impending responses after transplantation. In this study, we evaluated the role of the genetic predispositions of stromal-derived factor-1 (SDF1) [rs1801157 (G>A)] and CXC receptor 4 (CXCR4) [rs2228014 (C>T)] on renal allograft outcomes. A total of 335 pairs of recipients and donors were enrolled. Biopsy-proven acute rejection (BPAR) and long-term graft survival were traced. Despite similar allele frequencies between donors and recipients, minor allele of SDF1 rs1801157 (GA+AA) from donor, not from recipients, has a protective effect on the development of BPAR compared to wild type donor (GG) (P = 0.005). Adjustment for multiple covariates did not affect this result (odds ratio 0.39, 95% C.I 0.20-0.76, P = 0.006). CXCR4 rs2228014 polymorphisms from donor or recipient did not affect the incidence of acute rejection. SDF1 was differentially expressed in renal tubular epithelium with acute rejection according to genetic variations of donor rs1801157 showing higher expressions in the grafts from GG donors. Contrary to the development of BPAR, the presence of minor allele rs1801157 A, especially homozygocity, predisposed poor graft survival (P = 0.001). This association was significant after adjusting for several risk factors (hazard ratio 3.01; 95% C.I = 1.19-7.60; P = 0.020). The allelic variation of recipients, however, was not associated with graft loss. A donor-derived genetic polymorphism of SDF1 has influenced the graft outcome. Thus, the genetic predisposition of donor should be carefully considered in transplantation.
供体和受体之间的遗传相互作用可能决定移植后的潜在反应。在这项研究中,我们评估了基质衍生因子-1(SDF1)[rs1801157(G>A)]和 CXC 受体 4(CXCR4)[rs2228014(C>T)]的遗传倾向对肾移植结果的影响。共纳入 335 对供受者。追踪活检证实的急性排斥反应(BPAR)和长期移植物存活情况。尽管供体和受者之间的等位基因频率相似,但与野生型供体(GG)相比,供体 SDF1 rs1801157(GA+AA)的次要等位基因(GA+AA)对 BPAR 的发生具有保护作用(P=0.005)。调整多个协变量后,该结果仍然成立(比值比 0.39,95%置信区间 0.20-0.76,P=0.006)。供体或受者的 CXCR4 rs2228014 多态性均不影响急性排斥反应的发生。根据供体 rs1801157 的遗传变异,SDF1 在肾小管上皮细胞中表达不同,具有 GG 供体的移植物中表达较高。与 BPAR 的发生相反,SDF1 rs1801157 的次要等位基因 A 尤其是纯合性,易导致移植物存活不良(P=0.001)。在调整了几个危险因素后,这种关联仍然具有统计学意义(风险比 3.01;95%置信区间=1.19-7.60;P=0.020)。然而,受者的等位基因变异与移植物丢失无关。SDF1 的供体遗传多态性影响了移植物的结果。因此,在移植中应仔细考虑供体的遗传倾向。