Pharmacogenomics and pharmacogenetics of thiazolidinediones: role in diabetes and cardiovascular risk factors

Author:

Della-Morte David123,Palmirotta Raffaele3,Rehni Ashish K2,Pastore Donatella1,Capuani Barbara1,Pacifici Francesca1,De Marchis Maria Laura3,Dave Kunjan R2,Bellia Alfonso1,Fogliame Giuseppe4,Ferroni Patrizia3,Donadel Giulia1,Cacciatore Francesco5,Abete Pasquale6,Dong Chuanhui2,Pileggi Antonello7,Roselli Mario1,Ricordi Camillo7,Sbraccia Paolo14,Guadagni Fiorella3,Rundek Tatjana2,Lauro Davide14

Affiliation:

1. Department of Systems Medicine, School of Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy

2. Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA

3. Interinstitutional Multidisciplinary Biobank (BioBIM), Biomarker Discovery & Advanced Technologies (BioDAT), IRCCS San Raffaele Pisana, Rome, Italy

4. Division of Internal Medicine, Tor Vergata Foundation Hospital, Rome, Italy

5. IRCCS Salvatore Maugeri, Telese Terme (BN), Italy

6. Department of Clinical Medicine, Cardiovascular Science & Immunology, Cattedra di Geriatria, University of Naples Federico II, Naples, Italy

7. Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA

Abstract

The most important goal in the treatment of patients with diabetes is to prevent the risk of cardiovascular disease (CVD), the first cause of mortality in these subjects. Thiazolidinediones (TZDs), a class of antidiabetic drugs, act as insulin sensitizers increasing insulin-dependent glucose disposal and reducing hepatic glucose output. TZDs including pioglitazone, rosiglitazone and troglitazone, by activating PPAR-γ have shown pleiotropic effects in reducing vascular risk factors and atherosclerosis. However, troglitazone was removed from the market due to its hepatoxicity, and rosiglitazone and pioglitazone both have particular warnings due to being associated with heart diseases. Specific genetic variations in genes involved in the pathways regulated by TDZs have demonstrated to modify the variability in treatment with these drugs, especially in their side effects. Therefore, pharmacogenomics and pharmacogenetics are an important tool in further understand intersubject variability per se but also to assess the therapeutic potential of such variability in drug individualization and therapeutic optimization.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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