ArticleJournal, genetic engineering & biotechnology2018
Interaction of rs316019 variants of SLC22A2 with metformin and other drugs- an
Article in Journal, genetic engineering & biotechnology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- Role of solute carrier transporters in the biodistribution and toxicity of chemotherapeutic drugs.Pharmacological reviews · 2026Review
- Influence of OCT2 gene variants on metformin efficacy in type 2 diabetes: insights into pharmacogenomics and drug interactions.Journal of translational medicine · 2025Review
- PCK1 and SLC22A2 gene variants associated with response to metformin treatment in type 2 diabetes.PloS one · 2025Article
- Exome Sequence Data of Eight SLC Transporters Reveal ThatPharmaceuticals (Basel, Switzerland) · 2024Article
- The determination of the effect(s) of solute carrier family 22-member 2 (SLC22A2) haplotype variants on drug binding via molecular dynamic simulation systems.Scientific reports · 2022Article
- Genetic Association of Solute Carrier Transporter Gene Variants with Metformin Response.Balkan journal of medical genetics : BJMG · 2021Article
- The Impact of Genetic Polymorphisms in Organic Cation Transporters on Renal Drug Disposition.International journal of molecular sciences · 2020Review
- Mechanistic Models as Framework for Understanding Biomarker Disposition: Prediction of Creatinine-Drug Interactions.CPT: pharmacometrics & systems pharmacology · 2020Article
- Protein-protein interactions of drug uptake transporters that are important for liver and kidney.Biochemical pharmacology · 2019Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin is one of the first-line and most widely prescribed drugs to treat type 2 diabetes (T2D). Its clearance from circulation is mostly facilitated by SLC22A2 (OCT2) in the renal cells. SLC22A2 is a polyspecific organic cation transporter and mediate transport of structurally unrelated endogenous and exogenous compounds including many drugs. rs316019 (p.270A > S) is the most common variant of SLC22A2 with a frequency as high as 15% or more in many populations. The 270S form of SLC22A2 clears metformin from circulation at much reduced level compared to the 270A form. If accumulated, metformin increases plasma lactate level in a concentration-dependent manner which can lead to a condition known as metformin-associated lactic acidosis (MALA). MALA is a potentially life-threatening complication with a mortality rate of 30-50%. Pre-existing clinical conditions, such as renal impairment, sepsis, anoxia, etc may make individuals more prone to MALA. In this study, we used computational approaches to investigate the effect of 270A > S change in SLC22A2 on interaction with metformin and other drugs. Based on the structural models, all substrates bind to the same pocket of SLC22A2. The substrates fit better to the binding site of 270A form of SLC22A2. The binding site has a few core interacting residues, among which SER358 appears to be the most important. It is an
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.