Pharmacogenomics of Type 2 Diabetes Mellitus

Abstract

Diabetes mellitus is a complex metabolic disorder with multiple factors associated with its causation, outcome and response to treatment. Several researchers are working on identifying the genetic and non-genetic factors that are implicated in disease causation as well as response to therapy. It has been found that, some of the genetic factors such as ABCC8 and KCNJ11 polymorphisms are associated with disease causation as well as outcome of therapy with specific drugs. Presence of multiple associative factors have led to the realization of a much complex network of pathways that are involved in diabetes mellitus. In this review we discuss the genetic factors involved in type 2 diabetes mellitus and in its response to treatment with different classes of drugs. The genetic factors include single nucleotide polymorphisms in genes coding for drug metabolizing enzymes (e.g., CYP2C9), drug transporters (e.g., OCT1, OCT 2, MATE1, MATE2), receptors and channels such as ABCC8, KCNJ11. The net effect of all genetic variations in each individual patient determines the outcome of therapy. To translate pharmacogenetics in to clinical practice, it is needed to have evidence on the net effect of genetic polymorphisms.