Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
School of Pharmacy, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Int J Mol Sci. 2019 Apr 7;20(7):1720. doi: 10.3390/ijms20071720.
Insulin-sensitizer treatment with metformin is widely used in polycystic ovary syndrome (PCOS). However, the treatment effectiveness shows individual differences in PCOS patients. Organic cation transporter (OCT) 1 and 2 have been reported to mediate metformin transport in the liver and kidney, respectively. In this study, we investigated the association between the polymorphisms of and and the treatment effectiveness of metformin in PCOS patients. The single nucleotide polymorphisms (SNPs) of (rs683369 and rs628031) and (rs316019) were analyzed in 87 PCOS and 113 control women. Oral glucose tolerance tests (OGTTs), which represented metformin treatment response, were conducted at the start of treatment and after six-month treatment. The results demonstrated that the SNP frequencies of and were not associated with PCOS pathophysiology, and that the polymorphisms of and were not associated with the OGTT parameters at baseline. However, PCOS patients with the G allele of rs683369 and/or with the A allele of rs628031 had increased insulin sensitivity compared to those with wild-type genotype after receiving metformin treatment. Moreover, the interactions of metformin*SNP were significant in both rs683369 ( < 0.001) and rs628031 ( = 0.001) during the treatment period. Taken together, genetic polymorphisms of contributed to different metformin treatment responses, and further study is needed to establish personalized treatment programs using a pharmacogenomic algorithm approach in PCOS patients.
二甲双胍作为胰岛素增敏剂被广泛应用于多囊卵巢综合征（PCOS）的治疗。然而，在 PCOS 患者中，其治疗效果存在个体差异。有机阳离子转运蛋白（OCT）1 和 2 分别介导了二甲双胍在肝脏和肾脏中的转运。本研究旨在探讨 OCT 基因多态性与 PCOS 患者二甲双胍治疗效果的相关性。对 87 例 PCOS 患者和 113 例对照者的 OCT1(rs683369 和 rs628031)和 OCT2(rs316019)的单核苷酸多态性（SNP）进行了分析。在治疗开始时和治疗 6 个月后进行口服葡萄糖耐量试验（OGTT），以评估二甲双胍的治疗反应。结果表明，SNP 频率与 PCOS 的病理生理学无关，且多态性与基线时的 OGTT 参数无关。然而，与野生型基因型相比，接受二甲双胍治疗后，携带 rs683369 上 G 等位基因和/或 rs628031 上 A 等位基因的 PCOS 患者的胰岛素敏感性增加。此外，在治疗期间，二甲双胍*SNP 的相互作用在 rs683369（<0.001）和 rs628031（=0.001）中均具有统计学意义。综上所述，OCT 基因多态性与二甲双胍的治疗反应有关，需要进一步研究，以建立基于药物基因组学算法的个体化治疗方案。
