Xiao Di, Guo Yu, Li Xi, Yin Ji-Ye, Zheng Wei, Qiu Xin-Wen, Xiao Ling, Liu Rang-Ru, Wang Sai-Ying, Gong Wei-Jing, Zhou Hong-Hao, Liu Zhao-Qian
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology, Central South University and Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, China; Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang 421001, China.
Changsha Medical University Teaching Hospital, The People's Hospital of Liuyang, Liuyang 410300, China.
Int J Endocrinol. 2016;2016:4350712. doi: 10.1155/2016/4350712. Epub 2016 Feb 10.
Background. We aimed to investigate the distributive characteristics of SLC22A1 rs594709 and SLC47A1 rs2289669 polymorphisms and their influence on metformin efficacy in Chinese T2DM patients. Methods. The distributions of SLC22A1 rs594709 and SLC47A1 rs2289669 polymorphisms were determined in 267 T2DM patients and 182 healthy subjects. Subsequently, 53 newly diagnosed patients who received metformin monotherapy were recruited to evaluate metformin efficacy. Results. No significant difference was found between T2DM patients and healthy subjects in SLC22A1 rs594709 and SLC47A1 rs2289669 allele frequencies and genotype frequencies. After metformin treatment, SLC22A1 rs594709 GG genotype patients showed a higher increase in FINS (p = 0.015) and decrease in HOMA-IS (p = 0.001) and QUICKI (p = 0.002) than A allele carriers. SLC47A1 rs2289669 GG genotype patients had a higher decrease in TChol (p = 0.030) and LDL-C (p = 0.049) than A allele carriers. Among SLC22A1 rs594709 AA genotype, patients with SLC47A1 rs2289669 AA genotype showed a higher decrease in FBG (p = 0.015), PINS (p = 0.041), and HOMA-IR (p = 0.014) than G allele carriers. However, among SLC22A1 rs594709 G allele carriers, SLC47A1 rs2289669 AA genotype patients showed a higher decrease in TChol (p = 0.013) than G allele carriers. Conclusion. Our data suggest that SLC22A1 rs594709 and SLC47A1 rs2289669 polymorphisms may influence metformin efficacy together in Chinese T2DM patients.
背景。我们旨在研究SLC22A1基因rs594709位点和SLC47A1基因rs2289669位点多态性在中国2型糖尿病（T2DM）患者中的分布特征及其对二甲双胍疗效的影响。方法。测定267例T2DM患者和182例健康对照者中SLC22A1基因rs594709位点和SLC47A1基因rs2289669位点的多态性。随后，招募53例接受二甲双胍单药治疗的新诊断患者，评估二甲双胍的疗效。结果。T2DM患者与健康对照者在SLC22A1基因rs594709位点和SLC47A1基因rs2289669位点的等位基因频率和基因型频率上无显著差异。二甲双胍治疗后，SLC22A1基因rs594709位点GG基因型患者的空腹胰岛素（FINS）升高幅度更大（p = 0.015），胰岛素抵抗指数（HOMA-IS）和定量胰岛素敏感性指数（QUICKI）降低幅度更大（p = 0.001和p = 0.002），优于A等位基因携带者。SLC47A1基因rs2289669位点GG基因型患者的总胆固醇（TChol）和低密度脂蛋白胆固醇（LDL-C）降低幅度大于A等位基因携带者（p = 0.030和p = 0.049）。在SLC22A1基因rs594709位点AA基因型中，SLC47A1基因rs2289669位点AA基因型患者的空腹血糖（FBG）、餐后胰岛素（PINS）和胰岛素抵抗指数（HOMA-IR）降低幅度大于G等位基因携带者（p = 0.015、p = 0.041和p = 0.014）。然而，在SLC22A1基因rs594709位点G等位基因携带者中，SLC47A1基因rs2289669位点AA基因型患者的TChol降低幅度大于G等位基因携带者（p = 0.013）。结论。我们的数据表明，SLC22A1基因rs594709位点和SLC47A1基因rs2289669位点多态性可能共同影响中国T2DM患者二甲双胍的疗效。
