title: Role of genetic variation in the human sodium-glucose cotransporter 2 gene (SGLT2) in glucose homeostasis.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Interdisciplinary Centre for Clinical Research, University of Leipzig, Leipzig, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Enigk
authors.forename: Jana
authors.initials: J
authors.lastname: Breitfeld
authors.forename: Dorit
authors.initials: D
authors.lastname: Schleinitz
authors.forename: Kerstin
authors.initials: K
authors.lastname: Dietrich
authors.forename: Jan
authors.initials: J
authors.lastname: Halbritter
authors.forename: Antje
authors.initials: A
authors.lastname: Fischer-Rosinsky
authors.forename: Beate
authors.initials: B
authors.lastname: Enigk
authors.forename: Ines
authors.initials: I
authors.lastname: Müller
authors.forename: Joachim
authors.initials: J
authors.lastname: Spranger
authors.forename: Andreas
authors.initials: A
authors.lastname: Pfeiffer
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.forename: Peter
authors.initials: P
authors.lastname: Kovacs
authors.forename: Anke
authors.initials: A
authors.lastname: Tönjes
mesh_terms: D000368:Aged; D019540:Area Under Curve; D001786:Blood Glucose / Q000235:genetics* / Q000502:physiology; D015992:Body Mass Index; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005858:Germany / Q000453:epidemiology; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D051297:Sodium-Glucose Transporter 2 / Q000235:genetics*
chemical_list: D001786:Blood Glucose; D007328:Insulin; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2