SGLT2: a potential target for the pharmacogenetics of Type 2 diabetes?

The kidney has attracted the attention of diabetologists as an organ involved in the regulation of glucose homeostasis not only by gluconeogenesis, but also by renal glucose excretion. Sodium-glucose cotransporters (SGLTs), particularly SGLT2, are responsible for reabsorption of up to 99% of the filtered glucose. SGLT2 is coded by the SLC5A2 gene, which maps on chromosome 16. Pharmacological reduction of tubular glucose reabsorption results in improved glycemic control in Type 2 diabetic patients. Since the SGLTs reabsorb most of the filtered glucose (90%), it is not surprising that mutations in SLC5A2 cause familial renal glucosuria. A recent study pointed out a possible role of common genetic variation in SLC5A2 in the control of glucose homeostasis. SLC5A2 polymorphisms might therefore represent potential candidates for pharmacogenomic studies targeting the impact of these variants on the efficacy of antidiabetic treatment that is based on inhibition of SGLT2 activity.