ArticleGenome medicine2015
Global genetic analyses reveal strong inter-ethnic variability in the loss of activity of the organic cation transporter OCT1.
Article in Genome medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 3 of them syntheses that pooled it.
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Who cites it
54 citing papers in PubMed, 3 syntheses or guidelines pooled it, 108 citations in OpenAlex.
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- Prevention of Cisplatin-Induced Acute Kidney Injury: A Systematic Review and Meta-Analysis.Drugs · 2019Pooled it
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- Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans.Clinical pharmacology and therapeutics · 2025Trial
- A Prospective Population Pharmacokinetic Study on Morphine Metabolism in Cancer Patients.Clinical pharmacokinetics · 2017Trial
- Genetically Determined Loss-of-Function of the Organic Cation Transporter OCT1 Is Associated with Lower Liver Fat Content in Humans.International journal of molecular sciences · 2026Article
- Feed-Forward Deep Neural Networks Predict Substrate-Specific Effects of Transporter Variants to Explain Drug Response Variability.Clinical and translational science · 2026Article
- Role ofLife (Basel, Switzerland) · 2025Article
- The "specific" P-glycoprotein inhibitor zosuquidar (LY335979) also weakly inhibits human organic cation transporters.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Substrate-specific inhibition of organic cation transporter 1 revealed using a multisubstrate drug cocktail.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Evaluation of the effect of CYP2D6 and OCT1 polymorphisms on the pharmacokinetics of tramadol: Implications for clinical safety and dose rationale in paediatric chronic pain.British journal of clinical pharmacology · 2025Article
- Genetic Variants ofGenes · 2025Article
- Harnessing Pharmacogenomics in Clinical Research on Psychedelic-Assisted Therapy.Clinical pharmacology and therapeutics · 2025Review
- Metformin efficacy and tolerance according to genetic polymorphisms of organic cation transporter 1 in Tunisian patients with type 2 diabetes.Frontiers in endocrinology · 2025Article
- Effect of SLC22A1 polymorphism on the pharmacokinetics of proguanil in Korean: A semi-physiologic population pharmacokinetic approach.Clinical and translational science · 2024Article
- A Highly Sensitive UPLC-MS/MS Method for the Quantification of the Organic Cation Transporters' Mediated Metformin Uptake and Its Inhibition in Cells.Molecules (Basel, Switzerland) · 2024Article
- The full spectrum of SLC22 OCT1 mutations illuminates the bridge between drug transporter biophysics and pharmacogenomics.Molecular cell · 2024Article
- Impact of genetic variants in the solute carrier (Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Stereoselectivity in Cell Uptake by SLC22 Organic Cation Transporters 1, 2, and 3.Journal of medicinal chemistry · 2023Article
- Association of SLC22A1, SLC47A1, and KCNJ11 polymorphisms with efficacy and safety of metformin and sulfonylurea combination therapy in Egyptian patients with type 2 diabetes.Research in pharmaceutical sciences · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe organic cation transporter OCT1 (SLC22A1) mediates the uptake of vitamin B1, cationic drugs, and xenobiotics into hepatocytes. Nine percent of Caucasians lack or have very low OCT1 activity due to loss-of-function polymorphisms in OCT1 gene. Here we analyzed the global genetic variability in OCT1 to estimate the therapeutic relevance of OCT1 polymorphisms in populations beyond Caucasians and to identify evolutionary patterns of the common loss of OCT1 activity in humans.
methodsWe applied massively parallel sequencing to screen for coding polymorphisms in 1,079 unrelated individuals from 53 populations worldwide. The obtained data was combined with the existing 1000 Genomes data comprising an additional 1,092 individuals from 14 populations. The identified OCT1 variants were characterized in vitro regarding their cellular localization and their ability to transport 10 known OCT1 substrates. Both the population genetics data and transport data were used in tandem to generate a world map of loss of OCT1 activity.
resultsWe identified 16 amino acid substitutions potentially causing loss of OCT1 function and analyzed them together with five amino acid substitutions that were not expected to affect OCT1 function. The variants constituted 16 major alleles and 14 sub-alleles. Six major alleles showed improper subcellular localization leading to substrate-wide loss in activity. Five major alleles showed correct subcellular localization, but substrate-specific loss of activity. Striking differences were observed in the frequency of loss of OCT1 activity worldwide. While most East Asian and Oceanian individuals had completely functional OCT1, 80 % of native South American Indians lacked functional OCT1 alleles. In East Asia and Oceania the average nucleotide diversity of the loss-of-function variants was much lower than that of the variants that do not affect OCT1 function (ratio of 0.03) and was significantly lower than the theoretically expected heterozygosity (Tajima's D = -1.64, P < 0.01).
conclusionsComprehensive genetic analyses showed strong global variations in the frequency of loss of OCT1 activity with selection pressure for maintaining OCT1 activity in East Asia and Oceania. These results not only enable pharmacogenetically-based optimization of drug treatment worldwide, but may help elucidate the functional role of human OCT1.
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