Human organic cation transporter (OCT1 and OCT2) gene polymorphisms and therapeutic effects of metformin

Eriko Shikata, Rei Yamamoto, Hiroshi Takane, Chiaki Shigemasa, Tadasu Ikeda, Kenji Otsubo, Ichiro Ieiri

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Abstract

Organic cation transporters (OCTs) are responsible for the hepatic and renal transport of metformin. In this study we analyzed variants of OCT1 and OCT2 genes in 33 patients (24 responders and nine non-responders) based on the hypothesis that polymorphisms in both genes contribute to large inter-patient variability in the clinical efficacy of metformin. The sequences of the 5′-flanking and coding regions of the two genes of interest were screened by single-strand conformation polymorphism (SSCP) analysis. To compare the causative factors between responders and non-responders, we performed stepwise discriminant functional analysis. Age, body mass index (BMI) and treatment with lipid-lowering agents were demonstrated as positive predictors, and two mutations in the OCT1 gene, -43T > G in intron 1 and 408Met > Val (1222A > G) in exon 7, were negative and positive predictors, respectively, for the efficacy of metformin; the predictive accuracy was 55.5% (P < 0.05). Subsequent study indicated that OCT1 mRNA levels tended to be lower in human livers with the 408Met (1222A) variant, though the differences did not reach the level of significance. In this study it is suggested that OCT1 and OCT2 gene polymorphisms have little contribution to the clinical efficacy of metformin.

Original languageEnglish
Pages (from-to)117-122
Number of pages6
JournalJournal of Human Genetics
Volume52
Issue number2
DOIs
Publication statusPublished - Feb 1 2007

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Metformin
Therapeutic Uses
Cations
Genes
5' Flanking Region
Liver
Discriminant Analysis
Introns
Exons
Body Mass Index
Kidney
Lipids
Messenger RNA
Mutation

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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Human organic cation transporter (OCT1 and OCT2) gene polymorphisms and therapeutic effects of metformin. / Shikata, Eriko; Yamamoto, Rei; Takane, Hiroshi; Shigemasa, Chiaki; Ikeda, Tadasu; Otsubo, Kenji; Ieiri, Ichiro.

In: Journal of Human Genetics, Vol. 52, No. 2, 01.02.2007, p. 117-122.

Research output: Contribution to journalArticle

Shikata, Eriko ; Yamamoto, Rei ; Takane, Hiroshi ; Shigemasa, Chiaki ; Ikeda, Tadasu ; Otsubo, Kenji ; Ieiri, Ichiro. / Human organic cation transporter (OCT1 and OCT2) gene polymorphisms and therapeutic effects of metformin. In: Journal of Human Genetics. 2007 ; Vol. 52, No. 2. pp. 117-122.
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