Combined effects of CYP3A5*1, POR*28, and CYP3A4*22 single nucleotide polymorphisms on early concentration-controlled tacrolimus exposure in de-novo renal recipients

Kuypers, Dirk; de Loor, Henriette; Naesens, Maarten; Coopmans, Tamara; de Jonge, Hylke

doi:10.1097/FPC.0000000000000095

Combined effects of CYP3A51, POR28, and CYP3A4*22 single nucleotide polymorphisms on early concentration-controlled tacrolimus exposure in de-novo renal recipients

Author:

Kuypers, Dirk

de Loor, Henriette ; Naesens, Maarten ; Coopmans, Tamara ; de Jonge, Hylke

Keywords:

Science & Technology, Life Sciences & Biomedicine, Biotechnology & Applied Microbiology, Genetics & Heredity, Pharmacology & Pharmacy, CYP3A4*22, CYP3A4, CYP3A5*1, CYP3A5, POR, kidney transplantation, POR*28, single nucleotide polymorphism, tacrolimus, trough concentrations, SOLID-ORGAN TRANSPLANTATION, INTERNATIONAL CONSENSUS GUIDELINES, P450 OXIDOREDUCTASE, DOSE REQUIREMENTS, CYP3A5 GENOTYPE, CALCINEURIN-INHIBITORS, IN-VIVO, PHARMACOKINETICS, PHARMACOGENETICS, VARIANTS, Adult, Aged, Cohort Studies, Cytochrome P-450 CYP3A, Cytochrome P-450 Enzyme System, Female, Graft Rejection, Humans, Kidney Transplantation, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Tacrolimus, 0604 Genetics, 1115 Pharmacology and Pharmaceutical Sciences, 3105 Genetics, 3214 Pharmacology and pharmaceutical sciences

Abstract:

In a cohort of 298 de-novo renal recipients treated with a standard tacrolimus loading dose of 0.2 mg/kg, the combined effects of the CYP3A5*1, POR*28, and CYP3A4*22 genotypes on early tacrolimus exposure (C0), dose requirements, and achievement of the therapeutic target, C0, were examined. The incidence of clinical events (e.g. acute rejection, diabetes mellitus) was compared between genotypes.