Association Between OCT1, MATE1Gene Polymorphisms And Metformin Therapeutic Efficacy In Chinese Type2Diabetes Mellitus

Object:Metformin is one of the most widely used drug for type2diabetes(T2DM) therapy. Individual difference is quite common in metformin clinical use. organic cation transporter (OCT1) gene, expressed in liver, transports metformin into hepatocyte. Multidrug and toxin extrusion transporter1(MATE1) play important roles in excretion of metformin into bile and urine. This study aimed to evaluate effects of OCT1rs594709and MATE] rs2289669polymorphisms on metformin efficacy in Chinese type2diabetes mellitus (T2DM) patients.Method:We selected267T2DM patients and182healthy subjects to detect allele frequencies of OCT1rs594709and MATE1rs2289669polymorphisns in Chinese population. Fifty-three newly diagnosed Chinese T2DM patients were enrolled and took metformin monotherapy (500mg/d) for90consecutive days. The fasting and postprandial blood glucose, fasting and postprandial insulin, HbA1c and blood lipid in all subjects before and after metformin treatment were measured. OCT1rs594709and MATE1rs2289669genotypes of all the selected patients were identified by direct sequencing.Result:Frequencies of OCT1rs594709G allele in Chinese T2DM patients and healthy subjects were26.78%and28.57%, respectively. Frequencies of MATE1rs2289669G allele in Chinese T2DM patients and healthy subjects were47.19%and46.98%, respectively. There was a better metformin response on fasting insulin (FINS),(P<0.05) homeostasis model assessment of insulin sensitivity (HOMA-S)(P<0.05), quantitative insulin sensitivity check index (QUICKI)(P<0.05) in patients with OCT1rs594709A allele compared with GG genotypes. MATE1rs2289669GG genotyped patients showed a significantly higher decrease in Tchol (P<0.05) and LDL-c (P<0.05) compared with GA and AA genotypes. Among carriers with OCT1rs594709AA genotypes, patients with MATE1rs2289669AA genotype showed significant higher decrease of the fasting blood glucose (FBG)(P<0.05), postprandial insulin (PINS)(P<0.05), and homeostasis model assessment of insulin resistance (HOMA-IR)(P<0.05) than G allele carriers after metformin treatment. Among carriers with OCT1rs594709G alleles, patients with MATE1rs2289669AA genotype showed significant higher decrease of Tchol (P<0.05) than G allele carriers after metformin treatment.Conclusion:The OCT1rs594709polymorphism was associated with metformin therapeutic efficacy in Chinese T2DM patients. MATE1rs2289669had a significant interaction with OCT1rs594709, which could affect metformin drug response.