Department of Pharmaceutical Sciences and Interdepartmental Research Center of Pharmacogenetics and Pharmacogenomics (CRIFF), University of Piemonte Orientale, Largo Donegani 2, 28100, Novara, Italy.
Department of Pharmaceutical Sciences, University of Piemonte Orientale, Novara, Italy.
Sci Rep. 2020 Jul 30;10(1):12850. doi: 10.1038/s41598-020-69849-4.
Contrasting results exist on the association between CTLA-4 rs231775 and acute rejection in kidney transplant recipients. We herein conducted an updated systematic review with meta-analysis and trial sequential analysis (TSA) to clarify this relationship and to establish whether the current evidence is sufficient to draw firm conclusions. In addition, noteworthiness of significant pooled odds ratios (ORs) was estimated by false positive report probability (FPRP). A comprehensive search was performed through PubMed, Web of Knowledge, Cochrane Library and Open Grey up to October 2019. Fifteen independent cohorts, including a total of 5,401 kidney transplant recipients, were identified through the systematic review. Overall, no association was detected with the allelic (OR 1.07, 95% CI 0.88-1.30, P = 0.49), dominant (OR 0.94, 95% CI 0.73-1.22, P = 0.66) or the recessive (OR 1.18, 95% CI 0.97-1.43, P = 0.096) model of CTLA-4 rs231775. In each genetic model, the cumulative Z-curve in TSA crossed the futility boundary and entered the futility area. In addition, none of the significant genetic comparisons detected in the subsequent and sensitivity analyses or in previously reported meta-analyses were found to be noteworthy by FPRP. In conclusion, this study provides strong evidence that CTLA-4 rs231775 is not a clinically-relevant genetic risk determinant of acute rejection after renal transplantation.
CTLA-4 rs231775 与肾移植受者急性排斥反应之间的相关性存在相互矛盾的结果。本研究进行了更新的系统评价和荟萃分析及试验序贯分析（TSA），以阐明这种关系，并确定目前的证据是否足以得出明确的结论。此外，还通过虚假阳性报告概率（FPRP）估计了显著汇总优势比（OR）的重要性。通过PubMed、Web of Knowledge、Cochrane Library 和 Open Grey 进行了全面检索，检索时间截至 2019 年 10 月。通过系统评价确定了 15 个独立队列，共包括 5401 例肾移植受者。总体而言，未检测到 CTLA-4 rs231775 的等位基因（OR 1.07，95%CI 0.88-1.30，P=0.49）、显性（OR 0.94，95%CI 0.73-1.22，P=0.66）或隐性（OR 1.18，95%CI 0.97-1.43，P=0.096）模型与急性排斥反应相关。在每种遗传模型中，TSA 的累积 Z 曲线穿过无效边界并进入无效区域。此外，在随后的和敏感性分析或先前报道的荟萃分析中未发现任何显著的遗传比较通过 FPRP 被认为是重要的。总之，这项研究提供了强有力的证据表明，CTLA-4 rs231775 不是肾移植后急性排斥反应的一个具有临床相关性的遗传风险决定因素。
