Association between Polymorphisms of OCT1 and Metabolic Response to Metformin in Women with Polycystic Ovary Syndrome

• Published in: International journal of molecular sciences Vol. 20; no. 7; p. 1720
• Main Authors: Chang, Hui Hua, Hsueh, Yuan-Shuo, Cheng, Yung Wen, Ou, Huang-Tz, Wu, Meng-Hsing
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07.04.2019; MDPI
• Subjects: Adult; Alleles; Androgens; Antidiabetics; Blood pressure; Diabetes; Female; Gene polymorphism; Genotype; Genotype & phenotype; Glucose Tolerance Test; Humans; Hypoglycemic Agents - therapeutic use; Insulin Resistance; Menstruation; Metabolic response; Metabolism; Metformin; Metformin - therapeutic use; Nucleotides; Oct-2 protein; OCT1; Organic Cation Transporter 1 - genetics; Organic Cation Transporter 1 - metabolism; Organic Cation Transporter 2 - genetics; Ovulation; Patients; Polycystic ovary syndrome; Polycystic Ovary Syndrome - drug therapy; Polycystic Ovary Syndrome - genetics; Polymorphism; Polymorphism, Single Nucleotide - genetics; polymorphisms; Prospective Studies; Single-nucleotide polymorphism; metformin; OCT1; polymorphisms; polycystic ovary syndrome
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.