Rojas L1,2, Herrero MJ2, Bosó V2, Poveda JL2, Megías-Vericat JE2, Aliño SF2,3,4. 1Departmento de Medicina Interna, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile. 2Pharmacogenetic Unit. Drug Clinical Area. Hospital Universitari i Politècnic La Fe e Instituto de Investigación Sanitaria La Fe. Valencia. Spain. 3Clinical Pharmacology Unit. Drug Clinical Area, Hospital Universitari i Politècnic La Fe. Valencia. Spain. 4Department of Pharmacology. Faculty of Medicine. Universidad de Valencia. Spain.
Objective: Evaluate the impact of polymorphism of CYP3A5 6895A>G genotypes of donors and recipients on rates of chronic nephropathy (CN) in adults liver transplant recipients treated with tacrolimus. Methods: We included patients who were showed follow-up time at least three years post-transplantation. CN were diagnosed based on clinical criteria. For contrast the genotypes with the outcomes, we built two groups according to the ability to synthesize functional proteins: Expresser: CYP3A5*1. Non-expresser: CYP3A5 *3/*3. We performed multivariable regression to assess the contribution of others clinical variables. Results: 77 recipients and theirs donors were included. Allele frequencies were as follows: CYP3A5 genotypes, the *1/*1, *1/*3, and *3/*3 genotypes were detected in 4, 12, and 61 of donors, and 3, 10 and 64 of recipients, respectively. The incidence of CN was affected by the CYP3A5*1 allele in donors [*1/*1 and *1/*3 vs *3/*3: 37,5% vs 11%, p = 0,01; OR 4,2, 95% CI 1,02 to 19,8]. This effect is higher in recipients with CYP3A5 genotypes non expresser (50% vs 11%, p < 0,01; OR 8,2, 95% CI 1,34 to 45,6). We found increase of risk of nephropathy events by genes both polymorphisms of CYP3A5 in recipients and donors. Conclusion: CYP3A5*3/*3 genotype of donors provide more susceptible for developing CN associated with tacrolimus. This efects is more pronounced in recipients non exressers CYP3A5. It could be the result of toxic action of tacrolimus metabolites in renal tissue secondary a higher concentrations and metabolims of this drug.