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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.

SUBMITTER: Cargnin S

PROVIDER: S-EPMC7393166 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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

Cargnin Sarah S Galli Ubaldina U Shin Jae Il JI Terrazzino Salvatore S

Scientific reports 20200730 1

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 perfo ...[more]

PMID: 32732985

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Project description:Acute rejection (AR) after kidney transplant is one of the major obstacles to obtain ideal graft survival. Reliable molecular biomarkers for AR and renal allograft loss are lacking. This study was performed to identify novel long noncoding RNAs (lncRNAs) for diagnosing AR and predicting the risk of graft loss. The several microarray datasets with AR and nonrejection specimens of renal allograft downloaded from Gene Expression Omnibus database were analyzed to screen differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs). Univariate and multivariate Cox regression analyses were used to identify optimal prognosis-related DElncRNAs for constructing a risk score model. 39 common DElncRNAs and 185 common DEmRNAs were identified to construct a lncRNA-mRNA regulatory relationship network. DElncRNAs were revealed to regulate immune cell activation and proliferation. Then, 4 optimal DElncRNAs, ATP1A1-AS1, CTD-3080P12.3, EMX2OS, and LINC00645, were selected from 17 prognostic DElncRNAs to establish the 4-lncRNA risk score model. In the training set, the high-risk patients were more inclined to graft loss than the low-risk patients. Time-dependent receiver operating characteristics analysis revealed the model had good sensitivity and specificity in prediction of 1-, 2-, and 3-year graft survival after biopsy (AUC = 0.891, 0.836, and 0.733, respectively). The internal testing set verified the result well. Gene set enrichment analysis which expounded NOD-like receptor, the Toll-like receptor signaling pathways, and other else playing important role in immune response was enriched by the 4 lncRNAs. Allograft-infiltrating immune cells analysis elucidated the expression of 4 lncRNAs correlated with gamma delta T cells and eosinophils, etc. Our study identified 4 novel lncRNAs as potential biomarkers for AR of renal allograft and constructed a lncRNA-based model for predicting the risk of graft loss, which would provide new insights into mechanisms of AR.

Dataset Information

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

Publications

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

Similar Datasets

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