Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta-Analysis.
Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta-Analysis.
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DOI：
10.1002/cpt.567
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发表时间：
2017-06
影响因子：
6.7
通讯作者：
Pearson ER
中科院分区：
文献类型：
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作者：
Dujic T;Zhou K;Yee SW;van Leeuwen N;de Keyser CE;Javorský M;Goswami S;Zaharenko L;Hougaard Christensen MM;Out M;Tavendale R;Kubo M;Hedderson MM;van der Heijden AA;Klimčáková L;Pirags V;Kooy A;Brøsen K;Klovins J;Semiz S;Tkáč I;Stricker BH;Palmer C;'t Hart LM;Giacomini KM;Pearson ER
二甲双胍是治疗2型糖尿病（T2 D）的一线药物，其治疗反应具有高度可变性，部分原因可能是遗传因素。迄今为止，二甲双胍药物遗传学研究主要集中在二甲双胍转运蛋白基因变异的影响上，结果不一致。为了阐明这些变异体在T2 D患者二甲双胍血糖反应中的意义，我们在Metabolic Genetics Consortium（MetGen）的队列中进行了一项大规模Meta分析。在多达7，968名个体中分析了5种转运蛋白基因（有机阳离子转运蛋白[OCT]1，OCT 2，多药和毒素外排转运蛋白[MATE]1，MATE 2-K和OCTN 1）的9种候选多态性。在主要分析或探索性次要分析中，当根据可能的混杂基因型对患者进行分层或处方二甲双胍日剂量时，所有变体均未显示对二甲双胍应答的显著影响。我们的研究结果表明，候选转运蛋白基因变异对T2 D患者二甲双胍血糖反应的变异性几乎没有影响。
Therapeutic response to metformin, a first‐line drug for type 2 diabetes (T2D), is highly variable, in part likely due to genetic factors. To date, metformin pharmacogenetic studies have mainly focused on the impact of variants in metformin transporter genes, with inconsistent results. To clarify the significance of these variants in glycemic response to metformin in T2D, we performed a large‐scale meta‐analysis across the cohorts of the Metformin Genetics Consortium (MetGen). Nine candidate polymorphisms in five transporter genes (organic cation transporter [OCT]1, OCT2, multidrug and toxin extrusion transporter [MATE]1, MATE2‐K, and OCTN1) were analyzed in up to 7,968 individuals. None of the variants showed a significant effect on metformin response in the primary analysis, or in the exploratory secondary analyses, when patients were stratified according to possible confounding genotypes or prescribed a daily dose of metformin. Our results suggest that candidate transporter gene variants have little contribution to variability in glycemic response to metformin in T2D.