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Influence of CYP3A5 6986A > G and ABCB1 3435C > T Polymorphisms on Adverse Events Associated With Tacrolimus in Jordanian Pediatric Renal Transplant Patients
Author(s) -
Sy Sherwin K.B.,
Singh Rajendra P.,
Shilbayeh Sireen,
Zmeili Rawan,
Conrado Daniela,
Derendorf Hartmut
Publication year - 2013
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.22
Subject(s) - tacrolimus , medicine , cyp3a5 , adverse effect , single nucleotide polymorphism , genotype , gastroenterology , hazard ratio , transplantation , confidence interval , biology , genetics , gene
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.