A systematic review and meta-analysis recite the efficacy of Tacrolimus treatment in renal transplant patients in association with genetic variants of CYP3A5 gene.

Tacrolimus is an immunosuppressant with a narrow therapeutic index and pharmacokinetic variability. This variability may be attributed to genetic variants in gene associated with Tacrolimus metabolism. Studies focusing on genetic variants in the gene associated with Tacrolimus metabolism have been published, a meta-analysis of these published articles may provide a direction that can change the future research and clinical management of renal transplant patients. In this systematic review and meta-analysis, we have reviewed and analyzed the studies and clinical trials conducted to determine the association between genetic variants of and Tacrolimus metabolism from the PubMed database and clinical trials (www.clinicaltrials.gov). This meta-analysis also assessed the correlation of genotype (rs776746) with concentration/dose (C/D) of Tacrolimus in renal transplant patients. The 59 published articles on genetic association of the on Tacrolimus doses were reviewed for this systematic review. Meta-analysis showed that the Tacrolimus C/D ratio is significantly lower in the expressor group as compared with non-expressor in Asian, European as well as in mixed populations at any post-transplant period (P<0.0001). Our study further confirmed that the variant (rs776746) is clinically relevant for the dose determination of Tacrolimus. Variations in Tacrolimus C/D have been found to be significantly linked to the patient's genetic variant (rs776746). The addition of other genetic variants involved in the pharmacokinetic of Tacrolimus may determine efficient regimen for drug dose. Our meta-analysis confirmed that the genetic variant (rs776746) analysis is relevant in personalizing the Tacrolimus dose determination in renal transplant patients.