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RESEARCH PRODUCT

Meta-analysis and systematic review of the effect of the donor and recipient CYP3A5 6986A>G genotype on tacrolimus dose requirements in liver transplantation

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Objective A meta-analysis was carried out of publishedstudies on the effect of the CYP3A5 6986A>Gpolymorphism in liver donors and transplant recipientson tacrolimus pharmacokinetics.Methods Cohort studies that evaluated the relationshipbetween the CYP3A5 polymorphism in liver donors andtransplant recipients and tacrolimus, trough bloodconcentration normalized for the daily dose (C) perkilogram body weight (D) (C/D, ng/ml/mg/kg/day) up to1 year after transplantation, were included. Data were notrestricted by patient age or the language or journal ofpublication. A literature search was conducted using theCochrane Library, MEDLINE, EMBASE, and grey literature,and articles published up to 24 April 2013 were selected.Data were pooled (random-effects model), and the resultswere expressed as the mean difference of thecorresponding C/D ratios and 95% confidence intervals.Results Six studies involving donor genotypes (254patients) and four involving recipient genotypes (180patients) were ultimately included. The meta-analysisshowed the C/D ratio to be significantly higher inrecipients with nonexpresser donor variants at alltime points. In recipients, the variant did not influencethe C/D ratio.Conclusion The presence of the CYP3A5 6986A>Gpolymorphism in the donor affects tacrolimuspharmacokinetics in the recipient, although onlythe evidence available for the first month aftertransplantation was of adequate quality for demonstratinga significant difference. The evidence provided hereshows no effect of the recipient genotype; however,the quality of the evidence was low, thereby precludingthe drawing of firm conclusions. Pharmacogenetics andGenomics 23:509–517