Out Mattijs, Becker Matthijs L, van Schaik Ron H, Lehert Philippe, Stehouwer Coen D, Kooy Adriaan
Department of Internal Medicine, Bethesda Hospital Hoogeveen - Care Group Treant, Hoogeveen, The Netherlands.
Bethesda Diabetes Research Center Hoogeveen, Hoogeveen, The Netherlands.
Pharmacogenomics. 2018 Jun 1;19(8):715-726. doi: 10.2217/pgs-2018-0010. Epub 2018 May 23.
To determine the influence of polymorphisms on the effects of metformin on HbA1c, daily dose of insulin and metformin plasma concentration. Methods: In a post hoc analysis of a 4.3 year placebo-controlled randomized trial with 390 patients with Type 2 diabetes already on insulin, we analyzed the influence of polymorphisms in genes coding for ATM and the transporters OCT1 and MATE1. Outcome measures were a combined HbA1c + daily dose of insulin Z score and metformin plasma concentrations.
rs11212617 (ATM) was associated with an improved Z score and a lower metformin plasma concentration. In addition, the major allele of rs2289669 (MATE1) was also associated with an improved Z score.
The ATM SNP rs11212617 significantly affected the effect of metformin and metformin plasma concentration. Further research is needed to determine the clinical importance of these findings, in particular the effects on metformin plasma concentration.
确定基因多态性对二甲双胍降低糖化血红蛋白（HbA1c）水平、减少胰岛素每日用量及二甲双胍血药浓度的影响。方法：在一项为期4.3年的安慰剂对照随机试验的事后分析中，纳入390例已接受胰岛素治疗的2型糖尿病患者，分析编码共济失调毛细血管扩张症突变基因（ATM）以及转运体有机阳离子转运体1（OCT1）和多药及毒素外排蛋白1（MATE1）的基因多态性的影响。观察指标为糖化血红蛋白与胰岛素每日用量的联合Z评分以及二甲双胍血药浓度。结果：rs11212617（ATM）与Z评分改善及二甲双胍血药浓度降低相关。此外，rs2289669（MATE1）的主要等位基因也与Z评分改善相关。结论：ATM基因单核苷酸多态性（SNP）rs11212617显著影响二甲双胍的疗效及血药浓度。需要进一步研究以确定这些发现的临床意义，尤其是对二甲双胍血药浓度的影响。
