Are SGLT2 polymorphisms linked to diabetes mellitus and cardiovascular disease? Prospective study and meta-analysis
Are SGLT2 polymorphisms linked to diabetes mellitus and cardiovascular disease? Prospective study and meta-analysis
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DOI：
10.1042/bsr20190299
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发表时间：
2019-08-07
影响因子：
4
通讯作者：
Muendlein, Axel
中科院分区：
文献类型：
--
作者：
Drexel, Heinz;Leiherer, Andreas;Muendlein, Axel
抑制钠葡萄糖协同转运蛋白2（SGLT 2）可降低2型糖尿病（T2 DM）伴动脉粥样硬化心血管疾病患者的心血管发病率和死亡率。到目前为止，SGLT 2编码基因SLC 5A 2的常见遗传变异与葡萄糖稳态以及心血管疾病之间的联系尚未建立。因此，本研究旨在探讨SLC 5A 2单核苷酸多态性（SNPs）与2型糖尿病和冠状动脉疾病（CAD）的关系，并前瞻性地研究心血管事件的发生率。我们对1684例接受冠状动脉造影术的高危心血管患者（包括400例T2 DM患者）的SLC 5A 2标签SNP rs 9934336、rs3813008和rs3116150进行了基因分型。此外，我们进行了荟萃分析，结合本研究和文献的结果。变异rs 9934336与HbA 1c降低显著相关（P = 0.023）。此外，rs 9934336在单变量（OR = 0.82 [0.68-0.99]; P = 0.037）和多变量分析（OR = 0.79 [0.65-0.97]; P = 0.023）中与T2 DM的存在显著负相关。rs 9934336与T2 DM之间的关联在荟萃分析中得到证实，该分析包括先前两次观察的结果，这两次观察本身未能显示多态性与T2 DM的显著关联（OR = 0.86 [0.78-0.95]; P = 0.004）。多态性rs3813008和rs3116150与血糖参数和T2 DM均不相关。所检测的SNPs均与基线CAD存在或心血管事件的发生率无显著相关。我们的结论是，SLC 5A 2基因座内的遗传变异是显着相关的T2 DM的表现。
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. The present study, therefore, aimed to investigate SLC5A2 single nucleotide polymorphisms (SNPs) in relation to type 2 diabetes and coronary artery disease (CAD) and prospectively the incidence of cardiovascular events. We genotyped the SLC5A2 tagging SNPs rs9934336, rs3813008, and rs3116150 in a 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 HbA1c (P = 0.023). Further, rs9934336 was significantly inversely associated with the presence of T2DM 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 a meta-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 associated neither 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 of T2DM.