Impact of IL-6 and IL-10 Genotypes on Tacrolimus Dose Requirements in Kidney Transplant Recipients: Monte Carlo Analysis

Overview

Journal Pharmacogenomics

Specialties Genetics
Pharmacology

Date 2024 Jul 29

PMID 39069949

Authors

Nikola Stefanovic

Katarina Dankovic

Tatjana Cvetkovic

Stevan Vujic

Ivan Pavlovic

Tatjana Jevtovic-Stoimenov

Branka Mitic

Radmila Velickovic-Radovanovic

Affiliations

Soon will be listed here.

Abstract

IL-6 and IL-10 may affect the activity of cytochrome P450 (CYP) 3A enzymes involved in tacrolimus (Tac) metabolism. Moreover, the effect of IL-6 and IL-10 on Tac pharmacokinetics may differ with respect to the genetic variations in their genes. To examine the influence of IL-6 and IL-10 gene polymorphisms on Tac dose requirements and exposure over a 5-year period following kidney transplantation. Univariate and standard multivariate linear regression and Monte Carlo analysis were performed to investigate potential covariates influencing Tac dose-adjusted trough concentration (C/D) in various post-transplantation periods. IL-6 (-174G > C), IL-10 (-1082G > A, -819C > T and -592C > A) genotype, Tac daily dose, C, C/D and intrapatient variability data were collected from 113 patients. Multivariate regression analysis and accompanied Monte Carlo simulation underscore the importance of considering IL-6 -174G > C and IL-10 -1082G > A gene polymorphisms, alongside Tac metabolic phenotype and post-transplantation period, when tailoring Tac dosage regimen. This study provides valuable insights regarding the individualized adjustment of Tac treatment in various post-transplantation periods.

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