Effect of Genetic Variants in MATE1 and OCT3 on the Pharmacodynamics of Metformin in African Americans

The current study is part of a large multi-investigator grant to look at the pharmacogenetics of a number of membrane transporters. The investigators will study individuals with particular genotypes of the human organic cation transporter, (hOCT3), and the multidrug and toxin extrusion transporter, MATE1 to test the hypothesis that genetic variation in hOCT3 and hMATE1 are associated with variation in the pharmacokinetics and/or pharmacodynamics of the antidiabetic agent, metformin.

To investigate the potential association of polymorphic genetic variants MATE1 and OCT3 with altered response to metformin, a genotype to phenotype strategy is employed. Specifically, the investigators will evaluate this hypothesis in African-Americans, a population which has a high incidence of type 2 diabetes and which has high variant allele frequencies (44.5% for MATE1-66T\>C and 11.3% in OCT3-81G\>delGA) relative to other ethic groups. To assess the effects of these variants on metformin response, the investigators will measure metformin renal clearance (pharmacokinetics of metformin), and plasma glucose and insulin levels (pharmacodynamic response) in healthy and diabetic patients who carry either the reference or variant alleles.