Pharmacogenomics and pharmacogenetics of thiazolidinediones: role in diabetes and cardiovascular risk factors. (December 2014)

• Record Type: Journal Article
• Authors: Della-Morte, David; Palmirotta, Raffaele; Rehni, Ashish K; Pastore, Donatella; Capuani, Barbara; Pacifici, Francesca; De Marchis, Maria Laura; Dave, Kunjan R; Bellia, Alfonso; Fogliame, Giuseppe; Ferroni, Patrizia; Donadel, Giulia; Cacciatore, Francesco; Abete, Pasquale; Dong, Chuanhui; Pileggi, Antonello; Roselli, Mario; Ricordi, Camillo; Sbraccia, Paolo; Guadagni, Fiorella; Rundek, Tatjana; Lauro, Davide
• Is Part Of: Pharmacogenomics. Volume 15:Number 16(2014)
• Page Start: 2063
• Page End: 2082
• Publication Date: 2014-12
• Subjects: cardiovascular disease -- diabetes -- pharmacogenetics -- pharmacogenomics -- single nucleotide polymorphisms -- thiazolidinediones -- vascular risk factors; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs.14.162
• Languages: English
• ISSNs: 1462-2416

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.