Effect of pregnane X receptor polymorphisms on tacrolimus blood concentrations and the resulting adverse reactions in kidney transplantation recipients

Abstract

ABSTRACT.We investigated the effect of pregnane X receptor (PXR) polymorphisms on tacrolimus (FK506) blood trough concentrations and the associated adverse reactions in kidney transplantation recipients (KTRs). Polymerase chain reaction (PCR)-restriction fragment length polymorphism was used to detect the genotypes of single nucleotide polymorphism loci in 336 KTRs. The PXR six-base deletion mutation was classified using specific allele PCR, and the FK506 blood trough concentration in the KTRs was measured by chemiluminescent microparticle immunoassay. There were significant differences in adverse reactions resulting from FK506 in age, weight, body mass index (BMI) and treatment course (P < 0.05). Logistical regression 2 Z.P. Wang et al. Genetics and Molecular Research 15 (3): gmr.15038464 revealed that the FK506 treatment course and BMI were risk factors for hyperlipidemia, and the risk of hyperlipidemia increased 27.534 times when the BMI was less than 18.5. Moreover, age was also a risk factor leading to hyperglycemia. FK506 blood trough concentration and C 0 /D value had an impact on adverse reactions induced by hyperglycemia. The KTRs' PXR rs3842689, rs6785049, and rs1523127 mutation frequencies were 26.07, 11.79, and 16.07%, respectively. There was no statistically significant difference in the mutation frequency of each locus between the control group and the adverse reaction groups. Therefore, rs3842689, 7635G>A (rs6785049), and 24381C>A (rs1523127) PXR polymorphisms have no obvious impact on FK506; furthermore, the PXR rs3842689 wild-type homozygous WW genotype is a risk factor of FK506 and results in gastrointestinal reactions.

Effect of CYP3A4, CYP3A5, and ABCB1 Polymorphisms on Intravenous Tacrolimus Exposure and Adverse Events in Adult Allogeneic Stem Cell Transplant Patients

“…Although the primary role of tacrolimus in this setting is to prevent GVHD, we were unable to accurately depict the impact of pharmacogenetics or drug exposure on incidence of GVHD because patients received other immunosuppressants such as cyclophosphamide or mycophenolate mofetil post-transplant. Additionally, other genetic polymorphisms (eg, PXR, POR, as well as others) [18,[36][37][38] are not accounted for in this study, which could possibly explain some of the observed variability in i.v. tacrolimus exposure among this patient population.…”

Genotype‐Guided Model for Prediction of Tacrolimus Initial Dosing After Lung Transplantation

“…Candidate single nucleotide polymorphisms (SNPs) were mainly selected from previously reported literature, which may potentially affect tacrolimus pharmacokinetics in solid‐organ transplantation. All SNPs and their respective genes analyzed in this study are listed in Table S1 5,8,16–30 . For genotyping, briefly, a 0.5‐mL blood sample was collected and genomic DNA was extracted from ethylenediaminetetraacetic acid‐anticoagulated peripheral blood samples using a commercially available DNA purification kit (EasyPure Blood Genomic DNA Kit, Transgene Biotech).…”

“…All SNPs and their respective genes analyzed in this study are listed in Table S1. 5,8,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] For genotyping, briefly, a 0.5-mL blood sample was collected and genomic DNA was extracted from ethylenediaminetetraacetic acid-anticoagulated peripheral blood samples using a commercially available DNA purification kit (EasyPure Blood Genomic DNA Kit, Transgene Biotech). All samples with a call rate greater than 95% were genotyped using an Infinium Asian Screening Array-China Health Industry Alliance Bead chip (Illumina, Inc.) according to the Illumina Infinium HTS chip standard operating procedures.…”

CYP and SXR gene polymorphisms influence in opposite ways acute rejection rate in pediatric patients with renal transplant

“…It has been reported that SXR A7635G, an intronic single nucleotide polymorphism (SNP), is able to increase tacrolimus clearance [24,25]. On the other hand, studies in kidney transplant recipients showed no effect of this SNP on tacrolimus blood concentration [26,27].…”