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PPAR Research
Volume 2015, Article ID 415149, 10 pages
http://dx.doi.org/10.1155/2015/415149
Review Article

Pharmacogenomics of Drug Response in Type 2 Diabetes: Toward the Definition of Tailored Therapies?

1Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”, National Research Council, Via Pietro Castellino 111, 80131 Naples, Italy
2DiST, Department of Science and Technology, “Parthenope” University of Naples, Centro Direzionale, Isola C4, 80143 Naples, Italy

Received 3 March 2015; Accepted 24 May 2015

Academic Editor: Todd Leff

Copyright © 2015 Carla Pollastro et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Type 2 diabetes is one of the major causes of mortality with rapidly increasing prevalence. Pharmacological treatment is the first recommended approach after failure in lifestyle changes. However, a significant number of patients shows—or develops along time and disease progression—drug resistance. In addition, not all type 2 diabetic patients have the same responsiveness to drug treatment. Despite the presence of nongenetic factors (hepatic, renal, and intestinal), most of such variability is due to genetic causes. Pharmacogenomics studies have described association between single nucleotide variations and drug resistance, even though there are still conflicting results. To date, the most reliable approach to investigate allelic variants is Next-Generation Sequencing that allows the simultaneous analysis, on a genome-wide scale, of nucleotide variants and gene expression. Here, we review the relationship between drug responsiveness and polymorphisms in genes involved in drug metabolism (CYP2C9) and insulin signaling (ABCC8, KCNJ11, and PPARG). We also highlight the advancements in sequencing technologies that to date enable researchers to perform comprehensive pharmacogenomics studies. The identification of allelic variants associated with drug resistance will constitute a solid basis to establish tailored therapeutic approaches in the treatment of type 2 diabetes.