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

Pharmacogenomics. 2011 Aug;12(8):1119-26. doi: 10.2217/pgs.11.69. Epub 2011 Aug 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Area Under Curve
  • Blood Glucose / genetics*
  • Blood Glucose / physiology
  • Body Mass Index
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Gene Frequency
  • Genetic Variation
  • Germany / epidemiology
  • Glucose Tolerance Test
  • Homeostasis / genetics*
  • Homeostasis / physiology
  • Humans
  • Insulin / blood
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Sodium-Glucose Transporter 2 / genetics*


  • Blood Glucose
  • Insulin
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2