Why study drug response pharmacogenetics?
Variability in drug response, with respect to efficacy, tolerability, and safety, is a major issue for most drugs. Diabetes, like other complex diseases, is the product of many genes interacting with environmental factors. These interactions affect many pathways and even whole signaling networks in ways that cause disease. The promise of personalized medicine is that this complexity can be teased apart to refine the definition of disease, identify disease subtypes, and ultimately define biomarkers capable of discriminating between the patients most likely to benefit from a specific treatment and those unlikely to respond or likely to experience adverse events. One approach to this problem is to undertake pharmacogenetic studies to identify DNA variations in specific genes that are associated with response to treatment (Figure 1A). There have been many successes using this straightforward genetic approach, particularly with respect to genes that encode drug-metabolizing enzymes such as
