Department of Nephrology, Hennepin County Medical Center, University of Minnesota, Minneapolis, MN, USA.
Transplantation. 2010 Dec 27;90(12):1401-8. doi: 10.1097/TP.0b013e3182000085.
Acute rejection (AR) is associated with worse renal allograft outcomes. Therefore, this study investigated single-nucleotide polymorphisms (SNPs) to identify genetic variants associated with AR, accounting for center variation, in a multicenter, prospective, observation study.
We enrolled patients from six transplant centers, five in the United States and one in Canada. A total of 2724 SNPs were genotyped. We accounted for center variation in AR rates by stratifying by transplant center and using novel knowledge discovery methods.
There was significant center variation in AR rates across the six transplant sites (P<0.0001). Accounting for this difference and clinical factors independently associated with AR, we identified 15 novel SNPs associated with AR with stratification by transplant center (P<0.05). We also identified 15 novel SNPs associated with severity of tubulitis scores, after adjusting for transplant center and other clinical factors independently associated with severity of tubulitis (P<0.05). There was some overlap with one SNP associated with AR and also associated with severity of tubulitis, among the top 15 SNPs.
Center-to-center variation is a major challenge to genomic studies focused on AR. The SNPs associated with AR and severity of tubulitis in this study will need to be validated in independent cohort of kidney transplant recipients.
急性排斥反应（AR）与肾移植预后不良有关。因此，本研究通过多中心前瞻性观察研究，调查了单核苷酸多态性（SNP），以确定与 AR 相关的遗传变异，并考虑到中心的变异性。
我们从六个移植中心招募了患者，其中五个在美国，一个在加拿大。共对 2724 个 SNP 进行了基因分型。我们通过分层移植中心并使用新的知识发现方法来考虑 AR 率中的中心变异性。
六个移植地点的 AR 率存在显著的中心变异性（P<0.0001）。考虑到这种差异以及与 AR 独立相关的临床因素，我们确定了 15 个与 AR 相关的新的 SNP，这些 SNP 与移植中心分层有关（P<0.05）。我们还确定了 15 个与肾小管炎严重程度评分相关的新的 SNP，在调整与肾小管炎严重程度独立相关的移植中心和其他临床因素后（P<0.05）。在与 AR 相关的前 15 个 SNP 中，有一个与肾小管炎严重程度相关的 SNP 存在重叠。
以 AR 为重点的基因组研究的中心间差异是一个主要挑战。本研究中与 AR 和肾小管炎严重程度相关的 SNP 需要在独立的肾移植受者队列中进行验证。
