***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVES To study the prevalence and clinical significance of polymorphisms in the CYP3A5 and MDR1 genes in liver transplant patients and their donors ; to determine the relative importance of genes from the donor and the recipient ; to assess the relationship of polymorphisms with the variability of concentration/dose of tacrolimus for optimization and individualization regimens . MATERIAL S AND METHODS This prospect i ve study included 53 liver transplant recipients who received tacrolimus de novo .  CYP3A5 and MDR1 gene polymorphisms were identified in the donors and recipients using polymerase chain reaction . We collected indicator variables of graft function and the patient for 3 months after the transplantation : days 0 , 1 , 3 , 7 , 14 , 30 , 60 , and 90 . RESULTS The frequencies of CYP3A5 polymorphisms were : 90.6 % ( G/G ) , 9.4 % ( G/A ) and 0 % ( A/C ) in donors and 88.7 % ( G/G ) , 11.3 % ( G/A ) , and 0 % ( A/A ) in recipients . For the MDR1 gene , they were : 26.4 % ( C/C ) , 50.9 % ( C/T ) , and 22.6 % ( T/T ) in donors and 17.0 % ( C/C ) , 71.7 % ( C/T ) , and 11.3 % ( T/T ) in recipients . In the early days after transplant , G/A recipients from G/A donors did not reach the minimum drug levels . Between days 30 and 60 , G/G recipients from G/A donors required higher tacrolimus doses . G/G recipients ( CYP3A5 ) from C/T donors ( MDR1 ) had a lower frequency of renal dysfunction , the same rejection rate , and a higher rate of diabetes than the other groups . CONCLUSIONS For CYP3A5 , the presence of the A allele appeared to be related to greater requirements for tacrolimus in the early days after transplantation . Pharmacogenetics combined with pharmacodynamics may be a useful tool to adjust the concentration of tacrolimus depending on the absorption by the individual patient Objective Patients expressing the tacrolimus-metabolizing enzyme , cytochrome P450 ( CYP ) 3A5 , require more tacrolimus to reach target concentrations . We studied the influence of the CYP3A5 * 3 allele , which results in the absence of CYP3A5 protein , on tacrolimus dose and exposure , as well as the incidence of  biopsy-proven acute rejection ( BPAR ) after renal transplantation . Methods A total of 136 patients participating in a prospect i ve , r and omized-controlled clinical trial with the primary aim of comparing the efficacy of a fixed-dose versus a concentration-controlled mycophenolate mofetil immunosuppressive regimen  , were genotyped for CYP3A5 * 3 . The patients described herein , participated in a pharmacogenetic sub study and were all treated with mycophenolate mofetil , corticosteroids and tacrolimus . Tacrolimus predose concentrations ( C0 ) were measured on day 3 and 10 , and month 1 , 3 , 6 and 12 . Results Compared with CYP3A5 * 3/*3 individuals ( n=110 ) , patients carrying at least one CYP3A5 * 1 ( wild-type ) allele ( CYP3A5 expressers ; n=26 ) had a lower  tacrolimus C0 on day 3 only ( 16.6 versus 12.3 ng/ml , respectively ) , whereas dose-corrected tacrolimus C0 were significantly lower in the latter group at all time points . After day 3 , the overall daily tacrolimus dose was 68 % higher in CYP3A5 expressers ( P<0.001 ) . The incidence of BPAR was comparable between CYP3A5 expressers and nonexpressers ( 8 versus 16 % , respectively ; P=0.36 ) . Conclusion We conclude that patients expressing CYP3A5 need more tacrolimus to reach target concentrations and have a lower tacrolimus exposure shortly after transplantation . This delay in reaching target concentrations , however , did not result in an increased incidence of early BPAR and therefore , genotyping for CYP3A5 is unlikely to improve short-term transplantation outcome 
    Output:
    
The meta- analysis showed the C/D ratio to be significantly higher in recipients with nonexpresser donor variants at all time points .
In recipients , the variant did not influence the C/D ratio .
CONCLUSION The presence of the CYP3A5 6986A > G polymorphism in the donor affects  tacrolimus pharmacokinetics in the recipient , although only the evidence available for the first month after transplantation was of adequate quality for demonstrating a significant difference .