Meta-analysis shows no association of CYP3A5*3 variant with acute renal rejection in kidney-transplant patients receiving tacrolimus-based immunotherapy

Abstract

Life expectancy of kidney-transplanted patients is very low due to many causes, but allograft rejection is the central issue in organ transplantation. Immunosuppressive agents such as tacrolimus can solve this problem by inhibiting calcineurin. Tacrolimus has a very low therapeutic index and showed extensive intra-patient and inter-patient variability. The current meta-analysis is investigating the association between CYP3A5*3 (rs776746) variant and acute renal rejection (ARR) in tacrolimus treated population. To retrieve data, papers published on this subject were collected from PubMed, Google Scholar and Embase databases. Odds ratios (ORs) at 95% confidence intervals (CIs) were estimated to evaluate the association between CYP3A5*3 variant and risk of ARR. The pooled OR and CIs were calculated using random effect model. Heterogeneity was determined through Cochrane Q test and I-square statistic. Between-study heterogeneity was assessed through sensitivity analysis. Funnel plots and Egger’s test were performed to check publication bias. This meta-analysis included 27 papers comprising 790 ARR and 2981 no rejection subjects. No association between CYP3A5*3 and ARR risk was found in overall (Dominant model OR=1.25; 95% CI 0.96-1.64; P=0.097; I-square: 42%) or in subgroup ethnicities such as Asian (Dominant model OR=1.20; 95% CI 0.79- 1.85; P=0.302; I-square: 53.4%) and Caucasian (Dominant model OR=1.15; 95% CI 0.89-1.47; P=0.282; I-square: 33.7%) populations. There was no significant publication bias found in this meta-analysis. Based on current meta-analysis it can be concluded that there is no association between CYP3A5*3 variant and ARR in kidney-transplanted patients receiving tacrolimus-based immunotherapy

Keywords: Tacrolimus, CYP3A5, rs776746, acute renal rejection, meta-analysis