OBJECTIVE: Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) has been shown to transmit an inhibitory signal to T cells, which is a therapeutic target for acute rejection of kidney transplantation, and CTLA4 polymorphisms have also been considered as a potential risk factor. However, major studies have not yielded significant results. Thus, we conducted a meta-analysis of existing studies to boost their statistical power to clarify any associations between CTLA4 gene polymorphisms and acute rejection of kidney transplantation. METHODS: We searched for studies using PubMed, Embase and Academic Source Premier databases and checked the reference lists of all included studies for other relevant studies. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by both dominant and recessive genetic models. RESULTS: For CTLA4 +49A/G polymorphism, we found a marginally significant p value for A vs. G (OR=0.805, 95% CI, 0.677-0.957, p=0.014). No significant association between the -318C/T polymorphism and acute rejection risk was observed. CONCLUSION: The results suggest that the CTLA4 gene +49A/G polymorphism may be a possible genetic susceptibility locus for acute rejection. The results of the present meta-analysis may be limited by a number of factors including inadequate total sample size and poor statistics, and should be interpreted with caution. Further confirmation in large and well-designed studies are needed.
OBJECTIVE:Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) has been shown to transmit an inhibitory signal to T cells, which is a therapeutic target for acute rejection of kidney transplantation, and CTLA4 polymorphisms have also been considered as a potential risk factor. However, major studies have not yielded significant results. Thus, we conducted a meta-analysis of existing studies to boost their statistical power to clarify any associations between CTLA4 gene polymorphisms and acute rejection of kidney transplantation. METHODS: We searched for studies using PubMed, Embase and Academic Source Premier databases and checked the reference lists of all included studies for other relevant studies. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by both dominant and recessive genetic models. RESULTS: For CTLA4+49A/G polymorphism, we found a marginally significant p value for A vs. G (OR=0.805, 95% CI, 0.677-0.957, p=0.014). No significant association between the -318C/T polymorphism and acute rejection risk was observed. CONCLUSION: The results suggest that the CTLA4 gene +49A/G polymorphism may be a possible genetic susceptibility locus for acute rejection. The results of the present meta-analysis may be limited by a number of factors including inadequate total sample size and poor statistics, and should be interpreted with caution. Further confirmation in large and well-designed studies are needed.
Authors: William S Oetting; David P Schladt; Casey R Dorr; Baolin Wu; Weihua Guan; Rory P Remmel; David Iklé; Roslyn B Mannon; Arthur J Matas; Ajay K Israni; Pamala A Jacobson Journal: Transplantation Date: 2019-08 Impact factor: 4.939