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
OBJECTIVE: Inhibition of the renal sodium-glucose cotransporter 2 (SGLT2) is a novel concept in the therapy of diabetes mellitus. In this study, we first assessed whether common single nucleotide polymorphisms (SNPs) in the SGLT2-encoding gene SLC5A2 affect diabetes-related metabolic traits in subjects at risk for type 2 diabetes and, second, whether these have pharmacogenetic relevance by interfering with the response to empagliflozin treatment in patients with type 2 diabetes.
PATIENTS AND METHODS: Samples from a metabolically well-phenotyped cross-sectional study population (total N=2600) at increased risk for type 2 diabetes and pooled pharmacogenetic samples from patients from four phase III trials of empagliflozin (in total: 603 receiving empagliflozin, 305 receiving placebo) were genotyped for five common SNPs (minor allele frequencies ≥5%) present in the SLC5A2 gene locus.
RESULTS: In the cross-sectional study, none of the SLC5A2 SNPs significantly influenced metabolic traits such as body fat, insulin sensitivity/resistance, insulin release, HbA1c, plasma glucose, or systolic blood pressure when multiple testing was taken into account (all P≥0.0083). Further, no relevant effect on response to treatment with empagliflozin on HbA1c, fasting glucose, weight, or systolic blood pressure was observed for the SNPs tested in the pharmacogenetic study.
CONCLUSION: Common genetic variants in the SLC5A2 gene neither affects diabetes-related metabolic traits nor have a…
How strong is the evidence?
Evidence Hub reads this as a cross-sectional, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause. Reported size: 2,600 participants or records.
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