New challenges and promises in solid organ transplantation pharmacogenetics: the genetic variability of proteins involved in the pharmacodynamics of immunosuppressive drugs

Pharmacogenomics. 2016 Feb;17(3):277-96. doi: 10.2217/pgs.15.169. Epub 2016 Jan 22.

Abstract

Interindividual variability in immunosuppressive drug responses might be partly explained by genetic variants in proteins involved in the immune response or associated with IS pharmacodynamics. On a general basis, the pharmacogenetics of drug target proteins is less known and understood than that of proteins involved in drug disposition pathways. The aim of this review is to facilitate research related to the pharmacodynamics of the main immunosuppressive drugs used in solid organ transplantation. We elaborated a quality of evidence grading system based on a literature review and identified 'highly recommended', 'recommended' or 'potential' candidates for further research. It is likely that a number of additional rare variants might further explain drug response phenotypes in transplantation, and particularly the most severe ones. The advent of next-generation sequencing will help to identify those variants.

Keywords: calcineurin; gene polymorphism; inosine monophosphate dehydrogenase; mammalian target of Rapamycin; personalized medicine; pharmacology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Calcineurin Inhibitors / pharmacology*
  • Cyclosporine / pharmacology
  • Everolimus / pharmacology
  • Genetic Loci*
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Mycophenolic Acid / pharmacology
  • Organ Transplantation*
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide*
  • Proteins / genetics*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • Tacrolimus / pharmacology

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Proteins
  • Cyclosporine
  • Everolimus
  • TOR Serine-Threonine Kinases
  • Mycophenolic Acid
  • Tacrolimus