Impact of inducible co-stimulator gene polymorphisms on acute rejection in renal transplant recipients: An updated systematic review and meta-analysis

Abstract Background Acute rejection (AR) is an adverse predictor of long-term allograft survival. Previous studies have suggested that single-nucleotide polymorphisms in inducible co-stimulators may be associated with AR in kidney transplantation. Methods We searched for studies using PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in the dominant and recessive genetic models and the co-dominant and allele models. Results We observed significant associations between CTLA-4 + 49A/G, − 1147 C/T, − 1661 A/G, − 1722 T/C, CD28 IVS3 + 17 T/C polymorphisms and AR in kidney transplantation (+ 49A/G: OR: 0.79, 95% CI: 0.63–0.98; P  = 0.034; − 1147 C/T: OR: 0.19, 95% CI: 0.077, 0.48; P  = 0.081; − 1661 A/G: OR: 0.059, 95% CI: 0.042, 0.084; P  = 0.00; − 1722 T/C: OR: 0.32, 95% CI: 0.11, 0.97; P  = 0.044; CD28 IVS3 + 17 T/C: OR: 1.47, 95% CI: 1.04, 2.09; P  = 0.03). No significant associations between PDCD1, PTPN22 and CD86 polymorphisms and AR risk were identified. Conclusion + 49 G/A, − 1147 C/T, − 1661 A/G and − 1722 T/C polymorphisms in CTLA-4 and CD28 IVS3 + 17 T/C polymorphisms may be associated with the risk of AR occurrence in kidney transplantation. Further large, well-designed studies are urgently needed.