Influence of CYP3A5 6986A > G and ABCB1 3435C > T Polymorphisms on Adverse Events Associated With Tacrolimus in Jordanian Pediatric Renal Transplant Patients.
The aim of the study is to investigate the influence of ABCB1(3435) and CYP3A5(6986) polymorphisms, tacrolimus troughs and clinical factors on the time of adverse events associated with tacrolimus in pediatric kidney transplant patients. Clinical data, adverse events, tacrolimus troughs, corresponding doses, ABCB1 3435C > T and CYP3A5 6986A > G genotypes were collected from 38 pediatric kidney transplant patients in a retrospective study for over 2 years post-transplant. We used a marginal Cox proportional hazard model to evaluate the influence of clinical factors and single nucleotide polymorphisms (SNPs) on tacrolimus-associated adverse events. CYP3A5 genotype, the Bayesian predicted tacrolimus concentrations, hematocrit and mean corpuscular volume are significant risk factors of adverse events over a 2-year-period. CYP3A5*1 genotype was associated with 36% relative risk of CYP3A5*3/*3 genotype. In the 9-month period, the additional factor, ABCB1 3435TT genotype, was shown to be associated with 38% relative risk of the CC and CT genotypes. For graft loss, acute and chronic rejection, only tacrolimus concentration and hematocrit, but not CYP3A5 or ABCB1 polymorphisms, are important factors influencing their occurrences.
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Sherwin K B
SK
Sy
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Rajendra P
RP
Singh
Pediatric Department, King Hussain Medical Center, Amman, Jordan.|Clinical Pharmacy Department, Pharmacy College, Princess Nora University, Riyadh, Saudi Arabia.
Sireen
S
Shilbayeh
ICU Clinical Pharmacy Services, King Saud Medical City, Riyadh, Saudi Arabia.
Rawan
R
Zmeili
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Daniela
D
Conrado
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Hartmut
H
Derendorf
ABCB1; CYP3A5; adverse events; p-glycoprotein; risk factors; tacrolimus