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

Eriko Shikata1, Rei Yamamoto2, Hiroshi Takane1

  • 1Department of Hospital Pharmacy, Faculty of Medicine, Tottori University, Yonago, Japan.

Journal of Human Genetics
|November 18, 2006
PubMed

Insights

Genetic variations in organic cation transporter genes (OCT1 and OCT2) showed minimal impact on metformin

Area of Science:

  • Pharmacogenomics
  • Metabolism and Transport
  • Genetics

Background:

  • Organic cation transporters (OCTs), specifically OCT1 and OCT2, are crucial for metformin's hepatic and renal transport.
  • Significant inter-patient variability exists in metformin's clinical efficacy.
  • Genetic polymorphisms in OCT genes are hypothesized to influence this variability.

Purpose of the Study:

  • To investigate the association between OCT1 and OCT2 gene variants and metformin efficacy.
  • To identify genetic and clinical factors predicting patient response to metformin therapy.

Main Methods:

  • Analysis of OCT1 and OCT2 gene variants in 33 patients (24 responders, 9 non-responders).
  • Screening of gene regions using single-strand conformation polymorphism (SSCP) analysis.
  • Stepwise discriminant functional analysis to identify predictive factors for metformin efficacy.

Main Results:

  • Age, BMI, and lipid-lowering agent use were positive predictors of metformin efficacy.
  • Specific OCT1 mutations (-43T > G and 408Met > Val) showed predictive value (55.5% accuracy).
  • OCT1 mRNA levels were not significantly different between variants, suggesting limited functional impact.

Conclusions:

  • OCT1 and OCT2 gene polymorphisms appear to have a minor role in metformin's clinical efficacy.
  • Clinical factors like age and BMI, along with certain OCT1 mutations, contribute to predicting metformin response.

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