Validation of single nucleotide polymorphisms associated with acute rejection in kidney transplant recipients using a large multi-center cohort.
Validation of single nucleotide polymorphisms associated with acute rejection in kidney transplant recipients using a large multi-center cohort.
复制标题
使用大型多中心队列验证与肾移植受者急性排斥相关的单核苷酸多态性。
DOI：
10.1111/j.1432-2277.2011.01359.x
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
DeKAFInvestigators
中科院分区：
文献类型：
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作者：
Oetting,WilliamS;Schladt,DavidP;Leduc,RobertE;Jacobson,PamalaA;Guan,Weihua;Matas,ArthurJ;Israni,Ajay;DeKAFInvestigators
已经有许多报告提出遗传变异（通常以单核苷酸多态性（SNP）的形式）与急性排斥反应（AR）之间存在统计学显著相关性。不幸的是，有其他出版物报告，当对不同队列的接受者进行相同SNP分析时，与AR缺乏相关性。本报告的目的是试图在我们自己的肾移植受者队列中复制这些已发表的发现。我们分析了23种遗传变异，以前报道与AR有显著关联，使用了969名临床明确定义的肾移植受者的队列。在凝血因子V基因中，只有一个SNP rs6025（Leiden突变）显示出显著相关性，在种族调整分析中aP值为0.011，在多变量分析中aP值为0.0003。使用多变量分析，IMPDH 2中的另一个SNP rs11706052给出了0.044的适度P值，当考虑多重检验时，该值不显著。我们的研究结果表明，仔细验证先前报道的与AR的关联是必要的，除了候选基因研究之外的其他策略可以帮助识别与AR相关的致病遗传变异。
There have been numerous reports proposing a statistically significant association between a genetic variant, usually in the form of a single nucleotide polymorphism (SNP), and acute rejection (AR). Unfortunately, there are additional publications reporting a lack of association with AR when a different cohort of recipients was analyzed for the same SNP. The objective of this report was to attempt replication of these published finding in our own kidney allograft recipient cohort. We analyzed 23 genetic variants, previously reported to have a significant association with AR, using a cohort of 969 clinically well‐defined kidney transplant recipients. Only one SNP, rs6025 (Leiden mutation), within the coagulation factor V gene, showed a significant association with aP‐value of 0.011 in a race‐adjusted analysis and aP‐value of 0.0003 in multiple variable analysis. An additional SNP, rs11706052 in IMPDH2, gave a modestP‐value of 0.044 using multiple variable analysis, which is not significant when multiple testing is taken into consideration. Our results suggest that careful validation of previously reported associations with AR is necessary, and different strategies other than candidate gene studies can help to identify causative genetic variants associated with AR.