Pharmacogenetics of posttransplant diabetes mellitus

Pharmacogenomics J. 2017 Jun;17(3):209-221. doi: 10.1038/tpj.2017.1. Epub 2017 Mar 28.

Abstract

Many factors (physiological, pathological, environmental or genetic) are associated with variability in drug effect. Most patients respond to a standard treatment but the drug may be ineffective or toxic. In this review, we focused on genetic markers of posttransplant diabetes mellitus (PTDM) after renal transplantation, a frequent complication of immunosuppressive therapy and important risk factor of graft loss and mortality. An initial literature search identified 100 publications and among them 32 association studies were retrieved under 'Pharmacogenetics and PTDM'. Thirty-five variants in 25 genes with an impact on insulin secretion, disposition or effect were significantly associated with PTDM. The population studied, immunosuppressive regimen, follow-up, PTDM diagnostic and genetic variations tested were highly variable between studies. Although pharmacogenetic biomarkers are key tools of great promise for preventing toxicities and improving event-free survival rates, replication studies are required to select validated biomarkers linked to the occurrence of PTDM and select appropriate immusuppressive treatment to improve renal graft and patient outcome.

Publication types

  • Review

MeSH terms

  • Blood Glucose / metabolism
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / chemically induced
  • Diabetes Mellitus / genetics*
  • Genetic Predisposition to Disease
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Secretion
  • Kidney Transplantation / adverse effects*
  • Mutation*
  • Odds Ratio
  • Pharmacogenetics*
  • Pharmacogenomic Testing
  • Pharmacogenomic Variants*
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome

Substances

  • Blood Glucose
  • Immunosuppressive Agents
  • Insulin