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

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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.

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Most cited references 44

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Author and article information

Contributors

Salvatore Terrazzino: salvatore.terrazzino@uniupo.it

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 30 July 2020

Publication date PMC-release: 30 July 2020

Publication date Collection: 2020

Volume: 10

Electronic Location Identifier: 12850

Affiliations

[1 ]ISNI 0000000121663741, GRID grid.16563.37, Department of Pharmaceutical Sciences and Interdepartmental Research Center of Pharmacogenetics and Pharmacogenomics (CRIFF), , University of Piemonte Orientale, ; Largo Donegani 2, 28100 Novara, Italy

[2 ]ISNI 0000000121663741, GRID grid.16563.37, Department of Pharmaceutical Sciences, , University of Piemonte Orientale, ; Novara, Italy

[3 ]ISNI 0000 0004 0470 5454, GRID grid.15444.30, Department of Pediatrics, , Yonsei University College of Medicine, ; Seoul, Republic of Korea

Article

Publisher ID: 69849

DOI: 10.1038/s41598-020-69849-4

PMC ID: 7393166

PubMed ID: 32732985

SO-VID: 9a6fbbfc-5469-4b58-b640-f9f924ea57e0

License:

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