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• W1984565251 abstract "Objective The aim of this study was to determine the association between the renal clearance (CLrenal) 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. Methods 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. Results When analyzed alone, the c.808 (G>T) affected neither the CLrenal nor the secretory clearance (CLsec) of metformin. However, both CLrenal and CLsec were increased for the volunteers with minor alleles in c.808 (G>T) who were also homozygous for the reference variant g.-66T>C: CLrenal: GG, GT, and TT: 28.1, 34.5, and 44.8 l/h (P=0.004), respectively and CLsec: 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 CLrenal and CLsec 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. Conclusion 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." @default.
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• W1984565251 date "2013-10-01" @default.
• W1984565251 modified "2023-09-27" @default.
• W1984565251 title "A gene–gene interaction between polymorphisms in the OCT2 and MATE1 genes influences the renal clearance of metformin" @default.
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• W1984565251 doi "https://doi.org/10.1097/fpc.0b013e328364a57d" @default.
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