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- Title
Are SGLT2 polymorphisms linked to diabetes mellitus and cardiovascular disease? Prospective study and meta-analysis.
- Authors
Drexel, Heinz; Leiherer, Andreas; Saely, Christoph H.; Brandtner, Eva Maria; Geiger, Kathrin; Vonbank, Alexander; Fraunberger, Peter; Muendlein, Axel
- Abstract
Inhibition of the sodium glucose co-transporter 2 (SGLT2) reduces cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus (T2DM) with atherosclerotic cardiovascular disease. So far, a link between common genetic variations of the SGLT2 encoding gene SLC5A2 and glucose homeostasis as well as cardiovascular disease has not been established. This study, therefore, aimed to investigate SLC5A2 SNPs in relation to type 2 diabetes and coronary artery disease (CAD) and prospectively the incidence of cardiovascular events. We genotyped the SLC5A2 tagging single nucleotide polymorphisms (SNPs) rs9934336, rs3813008, and rs3116150 ina total of 1684 high risk cardiovascular patients undergoing coronary angiography, including 400 patients with T2DM. Additionally, we performed a meta-analysis combining results from the present study and the literature. Variant rs9934336 was significantly associated with decreased HbAlc (p=0.023). Further, rs9934336 was significantly inversely associated with the presence ofT2DM in univariate (OR=0.82 [0.68-0.99]; p=0.037) as well as in multivariate analysis (OR=0.79 [0.65-0.97]; p=0.023). The association between rs9934336 and T2DM was confirmed in ameta-analysis including results from two previous observations which by themselves had failed to show a significant association of the polymorphism with T2DM (OR=0.86 [0.78-0.95]; p=0.004). Polymorphisms rs3813008 and rs3116150 were neither associated with glycemic parameters nor with T2DM. None of the SNPs tested was significantly associated with the baseline presence of CAD or the incidence of cardiovascular events. We conclude that genetic variation within the SLC5A2 gene locus is significantly related to the manifestation ofT2DM.
- Subjects
DIABETES; CARDIOVASCULAR diseases; TYPE 2 diabetes; SINGLE nucleotide polymorphisms; LOCUS (Genetics); LONGITUDINAL method
- Publication
Bioscience Reports, 2019, Vol 39, Issue 8, p1
- ISSN
0144-8463
- Publication type
Article
- DOI
10.1042/BSR20190299