Review
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. May 29, 2020; 10(5): 90-103
Published online May 29, 2020. doi: 10.5500/wjt.v10.i5.90
Pharmacogenetics of immunosuppressant drugs: A new aspect for individualized therapy
Maurizio Salvadori, Aris Tsalouchos
Maurizio Salvadori, Department of Renal Transplantation, Careggi University Hospital, Florence 50139, Italy
Aris Tsalouchos, Nephrology and Dialysis Unit, Saints Cosmas and Damian Hospital, Pescia 51017, Italy
Author contributions: Salvadori M and Tsalouchos A contributed equally to the manuscript; Salvadori M designed the study, performed the last revision and provided answers to the reviewers; Tsalouchos A collected the data from the literature; Salvadori M and Tsalouchos A analyzed the collected data and wrote the manuscript.
Conflict-of-interest statement: Authors declare no conflicts of interest related to this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Maurizio Salvadori, MD, Professor, Department of Renal Transplantation, Careggi University Hospital, Viale Pieraccini 18, Florence 50139, Italy. maurizio.salvadori1@gmail.com
Received: January 10, 2020
Peer-review started: January 10, 2020
First decision: February 25, 2020
Revised: March 26, 2020
Accepted: April 23, 2020
Article in press: April 23, 2020
Published online: May 29, 2020
Processing time: 139 Days and 11.9 Hours
Abstract

In recent years, pharmacogenetics has emerged as an important tool for choosing the right immunosuppressant drug and its appropriate dose. Indeed, pharmacogenetics may exert its action on immunosuppressant drugs at three levels. Pharmacogenetics identifies and studies the genes involved in encoding the proteins involved in drug pharmacokinetics and in encoding the enzymes involved in drug degradation. Pharmacogenetics is also relevant in encoding the enzymes and proteins involved in codifying the transmembrane proteins involved in transmembrane passage favoring the absorption and intracellular action of several immunosuppressants. Pharmacogenetics concern the variability of genes encoding the proteins involved as immunosuppressant triggers in the pharmacodynamic pathways. Of course, not all genes have been discovered and studied, but some of them have been clearly examined and their relevance together with other factors such as age and race has been defined. Other genes on the basis of relevant studies have been proposed as good candidates for future studies. Unfortunately, to date, clear conclusions may be drawn only for those drugs that are metabolized by CYP3A5 and its genotyping before kidney, heart and lung transplantation is recommended. The conclusions of the studies on the recommended candidate genes, together with the development of omics techniques could in the future allow us to choose the right dose of the right immunosuppressant for the right patient.

Keywords: Immunosuppressant pharmacokinetics; Immunosuppressant pharmacodynamics; Immunosuppressant pharmacogenetics; Immunosuppressant pharmacogenomics; Transplantation; Immunosuppressant drugs

Core tip: The most common factors associated with drug response include age, sex, ancestry, concomitant drugs and liver or kidney diseases and drug pharmacogenetics. In general pharmacogenetics is the study of the variability of the response of a drug related to the complex gene arrays. More recently, the term pharmacogenomics has been introduced. This term in particular is related to omics studies. In recent years, pharmacogenetics that evaluates the drug response to genetic variations has emerged as an important tool for choosing the right therapeutic dose. According to the aim of the Precision Medicare Initiative, pharmacogenomics may contribute to providing the right drug at the right dose for the right patient.