Zhou Yong, Ye Weiwei, Wang Yi, Jiang Zhikui, Meng Xiangying, Xiao Qian, Zhao Qian, Yan Jian
Department of Endocrinology, Dahua Hospital Shanghai, China.
Int J Clin Exp Pathol. 2015 Aug 1;8(8):9533-42. eCollection 2015.
AIMS/HYPOTHESIS: Genetic variation in OCT1 can influence the glycemic response to metformin. We evaluated the effects of the OCT1 single-nucleotide polymorphisms (SNPs), rs1867351, rs4709400, rs628031, and rs2297374, on metformin efficacy in type-2 diabetes mellitus (DM) patients.
We performed a single-center prospective analysis of the distributions of these SNPs in a cohort of Han Chinese subjects in Shanghai, China (HCS), and evaluated the effects of each SNP on glycemic control in HCS DM patients following 3 months of incident metformin treatment.
The allele frequencies of rs4709400 and rs628031 in our HCS control group differed from those previously reported for Han Chinese subjects in Beijing (HCB), as well as those previously reported for Caucasians and Africans, whereas the allele frequencies of rs1867351 and rs2297374 were more similar to those in HCB subjects. The DM patients with the rs1867351 T/T or rs4709400 G/G genotype exhibited greater reductions in postprandial plasma glucose (PPG), compared to those with different genotypes of these SNPs. The DM patients with the rs2297374 C/T, rs4709400 G/G, or rs628031 G/G genotype exhibited greater reductions in fasting plasma glucose (FPG), and those with the rs1867351 T/T, rs628031 A/A, or rs2297374 C/T genotype exhibited greater reductions in HbA1c , compared to those with different genotypes of these SNPs. Conclusions /interpretation: The rs1867351, rs4709400, rs628031, and rs2297374 SNPs of OCT1 have selective effects on FPG, PPG, and HbA1c in HCS DM patients in response to metformin treatment. Future studies of these SNPs in larger samples of HCS DM patients are warranted.
目的/假设：有机阳离子转运体1（OCT1）的基因变异会影响二甲双胍的血糖反应。我们评估了OCT1单核苷酸多态性（SNP）rs1867351、rs4709400、rs628031和rs2297374对2型糖尿病（DM）患者二甲双胍疗效的影响。
我们对中国上海汉族人群队列（HCS）中这些SNP的分布进行了单中心前瞻性分析，并评估了在初治二甲双胍治疗3个月后，每个SNP对HCS DM患者血糖控制的影响。
我们HCS对照组中rs4709400和rs628031的等位基因频率与先前报道的北京汉族人群（HCB）以及先前报道的白种人和非洲人的等位基因频率不同，而rs1867351和rs2297374的等位基因频率与HCB人群更相似。与这些SNP不同基因型的DM患者相比，rs1867351 T/T或rs4709400 G/G基因型的DM患者餐后血浆葡萄糖（PPG）降低幅度更大。与这些SNP不同基因型的DM患者相比，rs2297374 C/T、rs4709400 G/G或rs628031 G/G基因型的DM患者空腹血糖（FPG）降低幅度更大，rs1867351 T/T、rs628031 A/A或rs2297374 C/T基因型的DM患者糖化血红蛋白（HbA1c）降低幅度更大。结论/解读：OCT1的rs1867351、rs4709400、rs628031和rs2297374 SNP对HCS DM患者在二甲双胍治疗后的FPG、PPG和HbA1c有选择性影响。有必要对更大样本的HCS DM患者进行这些SNP的进一步研究。
