The population-specific Thr44Met OCT3 coding variant affects metformin pharmacokinetics with subsequent effects on insulin sensitivity in C57Bl/6J mice
Authors' conclusion
These data provide evidence that the SLC22A3 rs8187715 variant accelerates metformin uptake rate in vivo. While this acutely improves insulin sensitivity, there was no increased effect of metformin with longer-term dosing. Thus, our finding of a high prevalence of this variant specifically in Māori and Pacific peoples identifies it as a potential population-specific pharmacogenetic marker with potential to guide metformin therapy in these peoples.
Study context
- Population
- 310 individuals with Māori and Pacific ancestry recruited in Aotearoa New Zealand; C57BL/6J knockin and wild-type miceMāori and Pacific ancestry
- Participants
- 310 individuals
- Comparison
- rs8187715 variant knockin mice vs wild-type control mice
- Outcome
- Prevalence (minor allele frequency) of rs8187715 in Māori and Pacific peoples, and its impact on metformin transport and efficacy in vivo
Methodological detailsgenotyping cohort, orthologous knockin mouse model
- Genotyping cohort
- Orthologous knockin mouse model
Main finding
As reported in the abstract
Minor allele frequency of the variant in Māori and Pacific participants
15.4%
Original publication
The population-specific Thr44Met OCT3 coding variant affects metformin pharmacokinetics with subsequent effects on insulin sensitivity in C57Bl/6J mice. Diabetologia. Published 18 October 2024. doi:10.
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