Role of genetic variation in the human sodium-glucose cotransporter 2 gene (SGLT2) in glucose homeostasis.

AIMS

Mutations in the sodium-glucose cotransporter 2 (SGLT2), as well as treatment with SGLT2 inhibitors result in reduced fasting glucose levels, HbA(1c) and BMI. We therefore investigated the effects of common genetic variation in SGLT2 on human Type 2 diabetes and related traits.

MATERIALS & METHODS: Four HapMap tagging SNPs covering the common genetic variation in SGLT2 (r² > 0.8 and minor allele frequency > 0.01) were genotyped for subsequent association studies on BMI, Type 2 diabetes and related metabolic traits in 1013 Sorbs (Germany). An independent cohort from Berlin (n = 2042) was taken for replication.

RESULTS

The rs9934336 G-allele was nominally associated with increased 30-min plasma glucose, 120-min insulin concentrations and AUC120min(glucose) during oral glucose tolerance test in 907 nondiabetic Sorbs (p < 0.05). In the combined analysis including the Sorbs and the Berlin cohort, rs9934336 was nominally associated with 120-min insulin concentrations (adjusted p < 0.05) in nondiabetic subjects (n = 2590).

CONCLUSION

Our data suggest a role of SGLT2 genetic variation in the regulation of glucose homeostasis and promote pharmacogenomic studies to clarify the efficacy of antidiabetic treatment by SGLT2 inhibitors.