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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Cohort Studies, European Continental Ancestry Group, Female, Genetic Variation, Genotype, Healthy Volunteers, Humans, Hypoglycemic Agents, Kidney, Linkage Disequilibrium, Male, Metformin, Organic Cation Transport Proteins, Organic Cation Transporter 2, Polymorphism, Single Nucleotide.
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Does a gene-gene interaction between polymorphisms in the OCT2 and MATE1 genes influence the renal clearance of metformin? Context: The aim of this study was to determine the association between the renal clearance (CL(renal)) of metformin in healthy Caucasian volunteers and the single-nucleotide polymorphism (SNP) c.808G>T (rs316019) in OCT2 as well as the relevance of the gene-gene interactions between this SNP and (a) the promoter SNP g.-66T>C (rs2252281) in MATE1 and (b) the OCT1 reduced-function diplotypes. Fifty healthy volunteers genotyped for the c.808G>T were enrolled in the study. The distribution was 25 GG, 20 GT, and 5 TT volunteers. The pharmacokinetics of a 500 mg single oral dose of metformin was studied. When analyzed alone, the c.808 (G>T) affected neither the CL(renal) nor the secretory clearance (CL(sec)) of metformin. However, both CL(renal) and CL(sec) were increased for the volunteers with minor alleles in c.808 (G>T) who were also homozygous for the reference variant g.-66T>C: CL(renal): GG, GT, and TT: 28.1, 34.5, and 44.8 l/h (P = 0.004), respectively and CL(sec): GG, GT, and TT: 21.4, 27.8, and 37.6 l/h (P = 0.005), respectively. In the volunteers with minor alleles in c.808 (G>T) who were also heterozygous for g.-66T>C, both CL(renal) and CL(sec) were found to be reduced (P < 0.028) when compared with volunteers with minor alleles in c.808 (G>T) carrying the g.-66T>C reference genotype.
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We report counteracting effects of the c.808 (G>T) and g.-66T>C on the renal elimination of metformin. When adjusted for the genetic variation g.-66T>C, our results suggest that c.808 (G>T) could have a dominant genotype to phenotype correlation. Final Decision: yes