title: Impact of PPARA and POR polymorphisms on tacrolimus pharmacokinetics and new-onset diabetes in kidney transplant recipients.
abstract: Recent efforts have been made to identify genetic markers of CYP3A4 enzymatic activity within genes encoding for regulatory elements. The aim of the current study was to investigate the impact of polymorphism of PPARA and POR genes on tacrolimus (TAC) dose-adjusted trough concentration and risk of new-onset diabetes after transplantation (NODAT). A total of 241 White kidney transplant patients were genotyped for three functional single nucleotide polymorphisms: rs1057868 (*28) in POR, rs4253728:G>A, and rs4823613:A>G in PPARA. No significant genotype-dependent differences in TAC dose-adjusted trough concentration were observed for either POR or PPARA variants. No significant differences in the incidence of NODAT were observed between patients stratified by PPARA and POR genotypes. The frequency of NODAT among PPARA rs4253728 AA homozygotes (42%) was higher compared with heterozygotes (22%) and GG homozygotes (19%), but the difference was not significant. Testing TAC-medicated renal transplant recipients for POR and PPARA variants seems to have limited clinical application.
authors.affiliation: aDepartment of Experimental and Clinical Pharmacology, Pomeranian Medical University bClinical Department of Nephrology and Dialysis, Marie Curie Regional Hospital, Szczecin, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Kurzawski
authors.forename: Damian
authors.initials: D
authors.lastname: Malinowski
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Dziewanowski
authors.forename: Marek
authors.initials: M
authors.lastname: Droździk
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D048909:Diabetes Complications / Q000209:etiology / Q000235:genetics*; D003920:Diabetes Mellitus / Q000235:genetics; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000235:genetics*; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D047493:PPAR alpha / Q000235:genetics*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D012307:Risk Factors; D016559:Tacrolimus / Q000493:pharmacokinetics*
chemical_list: D047493:PPAR alpha; D003577:Cytochrome P-450 Enzyme System; D016559:Tacrolimus