Influence of common polymorphisms in the SLC5A2 gene on metabolic traits in subjects at increased risk of diabetes and on response to empagliflozin treatment in patients with diabetes

Abstract

Common genetic variants in the SLC5A2 gene neither affects diabetes-related metabolic traits nor have a clinically relevant impact on response to treatment with the SGLT2 inhibitor empagliflozin.

Common variation in the sodium/glucose cotransporter 2 gene SLC5A2 does neither affect fasting nor glucose-suppressed plasma glucagon concentrations

“…Therefore, we analysed whether common genetic variation in the human SGLT2 gene SLC5A2 associates with fasting and glucose-suppressed circulating glucagon concentrations. We analysed the four tagging SNPs that were recently tested in a larger study population (N = 2,229) from our TÜF study for association with glycemic traits, insulin sensitivity, insulin secretion, blood pressure, and glomerular filtration [9]. In this earlier study, we found nominal associations of SNP rs3116150 with fasting glycemia, glucose excursions during the 5-point OGTT (AUC glucose), and systolic blood pressure [9].…”

“…We analysed the four tagging SNPs that were recently tested in a larger study population (N = 2,229) from our TÜF study for association with glycemic traits, insulin sensitivity, insulin secretion, blood pressure, and glomerular filtration [9]. In this earlier study, we found nominal associations of SNP rs3116150 with fasting glycemia, glucose excursions during the 5-point OGTT (AUC glucose), and systolic blood pressure [9]. Three of our four SNPs (rs3116150, rs3813008, rs9934336) were also studied by Enigk et al .…”

“…All study participants were assessed for medical history, smoking status, and alcohol consumption habits, and underwent physical examination, routine blood tests, and oral glucose tolerance tests (OGTTs). In this at-risk population, 2,229 subjects who (i) donated DNA, (ii) had complete 5-point OGTT data sets, and (iii) had documented absence of medication modulating glucose tolerance, insulin sensitivity, or insulin secretion were successfully genotyped for SLC5A2 variants in the course of a recent investigation [9]. From this well phenotyped and genotyped group, a study population of 375 subjects was selected on the basis of available plasma glucagon measurements.…”

“…Selection of the tagging SNPs and their genotyping were recently described in detail [9]. In brief, the four common SLC5A2 SNPs, i.e., rs9924771 G/A and rs9934336 G/A in intron 1 and rs3813008 G/A and rs3116150 G/A in intron 5, were identified as tagging SNPs by in silico analysis of publicly available linkage disequilibrium data from the 1000 Genomes Project (CEU population).…”

“…Prompted by this novel role of SGLT2 in the regulation of glucagon release, we tested whether recently reported common genetic variation in the human SGLT2 gene SLC5A2 [9] is associated with circulating glucagon concentrations during a 5-point oral glucose tolerance test (OGTT) in subjects at risk for type-2 diabetes.…”