Genetic variation in the organic cation transporter 1 is associated with metformin response in patients with diabetes mellitus
Genetic variation in the organic cation transporter 1 is associated with metformin response in patients with diabetes mellitus
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DOI：
10.1038/tpj.2009.15
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发表时间：
2009-08-01
影响因子：
2.8
通讯作者：
Stricker, B. H. C.
中科院分区：
文献类型：
--
作者：
Becker, M. L.;Visser, L. E.;Stricker, B. H. C.
由SLC 22 A1基因编码的有机阳离子转运蛋白1负责肝细胞中抗高血糖药物二甲双胍的摄取。我们评估了SLC 22 A1基因的遗传变异是否与二甲双胍的降糖作用相关。确定了鹿特丹研究中的二甲双胍使用者，其HbA 1 c测量值可用。分析SLC 22 A1基因11个标记单核苷酸多态性与HbA 1c水平变化之间的关联。本研究样本中共纳入102例二甲双胍使用者。除rs622342 A > C多态性外，未观察到二甲双胍反应的显著差异。对于rs622342处的每个次要C等位基因，HbA 1c水平降低0.28%（95% CI 0.09-0.47，P = 0.005）。Bonferroni校正后，P值为0.050。总之，SLC 22 A1基因rs622342的遗传变异与二甲双胍在糖尿病患者中的降糖作用相关。药物基因组学杂志（2009）9，242-247; doi：10.1038/tpj.2009.15; 2009年4月21日在线发表
The organic cation transporter 1, encoded by the SLC22A1 gene, is responsible for the uptake of the anti-hyperglycaemic drug, metformin, in the hepatocyte. We assessed whether a genetic variation in the SLC22A1 gene is associated with the glucose-lowering effect of metformin. Incident metformin users in the Rotterdam Study, whose HbA1c measurements were available, were identified. Associations between 11 tagging single nucleotide polymorphisms in the SLC22A1 gene and change in the HbA1c level were analyzed. A total of 102 incident metformin users were included in this study sample. Except for the rs622342 A > C polymorphism, no significant differences in metformin response were observed. For each minor C allele at rs622342, the reduction in HbA1c levels was 0.28% less (95% CI 0.09-0.47, P = 0.005). After Bonferroni correction, the P-value was 0.050. To conclude, genetic variation at rs622342 in the SLC22A1 gene was associated with the glucose-lowering effect of metformin in patients with diabetes mellitus. The Pharmacogenomics Journal (2009) 9, 242-247; doi: 10.1038/tpj.2009.15; published online 21 April 2009