CTLA-4 rs231775 and risk of acute renal graft rejection: an updated meta-analysis with trial sequential analysis

Sarah Cargnin; Ubaldina Galli; Jae Il Shin; Salvatore Terrazzino

doi:10.1038/s41598-020-69849-4

CTLA-4 rs231775 and risk of acute renal graft rejection: an updated meta-analysis with trial sequential analysis

Sarah Cargnin, Ubaldina Galli, Jae Il Shin, Salvatore Terrazzino

Department of Pediatrics

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

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.

Original language	English
Article number	12850
Journal	Scientific reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-69849-4
Publication status	Published - 2020 Dec 1

Bibliographical note

Funding Information:
The authors thank Dr. William S. Oetting (Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN.) for his kind availability to provide genotype data. S.C. holds a temporary research fellowship (Bando Fondazione CRT, ID 393), supported by University of Piemonte Orientale, which is deeply acknowledged. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Publisher Copyright:
© 2020, The Author(s).

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10.1038/s41598-020-69849-4

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@article{b18d9b565e9b489b9653fd84391ea2b9,

title = "CTLA-4 rs231775 and risk of acute renal graft rejection: an updated meta-analysis with trial sequential analysis",

abstract = "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.",

author = "Sarah Cargnin and Ubaldina Galli and Shin, {Jae Il} and Salvatore Terrazzino",

note = "Funding Information: The authors thank Dr. William S. Oetting (Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN.) for his kind availability to provide genotype data. S.C. holds a temporary research fellowship (Bando Fondazione CRT, ID 393), supported by University of Piemonte Orientale, which is deeply acknowledged. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Publisher Copyright: {\textcopyright} 2020, The Author(s).",

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doi = "10.1038/s41598-020-69849-4",

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AU - Cargnin, Sarah

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AU - Shin, Jae Il

AU - Terrazzino, Salvatore

N1 - Funding Information: The authors thank Dr. William S. Oetting (Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN.) for his kind availability to provide genotype data. S.C. holds a temporary research fellowship (Bando Fondazione CRT, ID 393), supported by University of Piemonte Orientale, which is deeply acknowledged. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Publisher Copyright: © 2020, The Author(s).

PY - 2020/12/1

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N2 - 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.

AB - 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.

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CTLA-4 rs231775 and risk of acute renal graft rejection: an updated meta-analysis with trial sequential analysis

Abstract

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