A gene–gene interaction between polymorphisms in the OCT2 and MATE1 genes influences the renal clearance of metformin

• DOI: 10.1097/fpc.0b013e328364a57d
• Publication Date: 2013-07-18T11:20:31Z
• Authors: Mette M.H. Christ...; Rasmus S. Pedersen; Tore B. Stage; Charlotte Brasch-...; Flemming Nielsen; Per Damkier; Henning Beck-Nielsen; Kim Brøsen
• Keywords: Minor allele frequency; SNP

Objective The aim of this study was to determine the association between renal clearance (CLrenal) metformin in healthy Caucasian volunteers and single-nucleotide polymorphism (SNP) c.808G>T (rs316019) OCT2 as well relevance gene–gene interactions SNP (a) promoter g.-66T>C (rs2252281) MATE1 (b) OCT1 reduced-function diplotypes. Methods Fifty genotyped for were enrolled study. distribution 25 GG, 20 GT, 5 TT volunteers. pharmacokinetics a 500 mg single oral dose studied. Results When analyzed alone, c.808 (G>T) affected neither CLrenal nor secretory (CLsec) metformin. However, both CLsec increased with minor alleles who also homozygous reference variant g.-66T>C: CLrenal: TT: 28.1, 34.5, 44.8 l/h (P=0.004), respectively CLsec: 21.4, 27.8, 37.6 (P=0.005), respectively. In heterozygous g.-66T>C, found be reduced (P<0.028) when compared carrying genotype. Conclusion We report counteracting effects on elimination adjusted genetic variation our results suggest that could have dominant genotype phenotype correlation.