What you carry at this position in your DNA and what research says about it.
Metformin Response: 5/10 evidence, 12 publications.
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Sample genotype (not yours): A/A
Altered Medication Response and Higher Side Effect Risk
Processing of metformin, imatinib, and lamotrigine may be less efficient. This can lead to reduced drug efficacy and an increased risk of gastrointestinal side effects.
What this genotype means: Poorer response to metformin; Suboptimal response to imatinib; Slower metabolism of lamotrigine.
Sample genotype (not yours): A/G
Sample genotype (not yours): G/G
Better Metformin Response with Altered Imatinib Processing
Metformin therapy is highly effective, but processing of the oncology drug imatinib is altered. This can lead to slower imatinib metabolism and higher toxicity risk.
What this genotype means: Enhanced response to metformin; Slower metabolism of imatinib; Increased risk of imatinib toxicity.
Gene function and biological role
Gene Function: The SLC22A1 gene encodes organic cation transporter 1 (OCT1), a critical protein primarily expressed in the liver [1]. This transporter plays a fundamental role in the cellular uptake of various organic cations, including essential endogenous compounds and clinically vital drugs [1]. It is particularly well-known for facilitating the transport of metformin, the first-line therapy for type 2 diabetes, into hepatocytes where the drug exerts its glucose-lowering effects [2]. Additionally, OCT1 is involved in the uptake of other therapeutic agents, such as the tyrosine kinase inhibitor imatinib used in leukemia treatment [3]. Variations in this gene can significantly alter transporter activity, leading to substantial differences in drug efficacy and safety profiles among patients [2] [3].
Variant Impact: The rs628031 variant represents a missense mutation in the SLC22A1 gene, resulting in a substitution of methionine with valine at position 408 of the OCT1 protein (p.Met408Val). This amino acid change occurs in a region that can influence the transporter's structural stability and substrate binding affinity [3]. While some laboratory studies suggest the p.Met408Val substitution does not completely abolish transport function, clinical evidence indicates it alters the pharmacokinetics of several medications [3] [2]. Specifically, the presence of the valine-encoding G allele or methionine-encoding A allele is associated with varying rates of drug clearance and cellular uptake [2] [4]. Consequently, this single nucleotide polymorphism is a key focus of pharmacogenomic research for diabetes and oncology therapies [2] [4].
Key Insight: This single genetic letter change simultaneously influences how your body processes a common diabetes medication, a leukemia drug, and an epilepsy treatment.
Location: SLC22A1. Chromosome 6 · 6q25.3 · 160.1 Mb
Estimated prevalence by population
Global 12.7%; European 16.4%; African 7.4%; East Asian 7.5%; South Asian 13.9%; Americas 7.0%; Ashkenazi 11.2%; Finnish 20.2%; Middle Eastern 6.2%; Amish 14.9%.
Estimated AA genotype frequency.
Global 44.5%; European 48.2%; African 39.6%; East Asian 39.8%; South Asian 46.8%; Americas 38.9%; Ashkenazi 44.6%; Finnish 49.5%; Middle Eastern 37.3%; Amish 47.4%.
Estimated AG genotype frequency.
Global 42.8%; European 35.4%; African 53.1%; East Asian 52.8%; South Asian 39.3%; Americas 54.1%; Ashkenazi 44.2%; Finnish 30.3%; Middle Eastern 56.5%; Amish 37.7%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Pharmacogenomics
Diabetes Medication Response
Metformin Response. Evidence: 5/10. Source: PMID 36853844. Poorer Response.
Sulfonylurea Side Effects. Evidence: 5/10. Source: PMID 39005567. Higher GI Toxicity.
Chemotherapy Response
Imatinib Response. Evidence: 5/10. Source: PMID 29427770. Poorer Response.
Antiepileptic & Mood-Stabilizer Response
Lamotrigine Metabolism. Evidence: 5/10. Source: PMID 27610747. Slower Metabolism.
Nutrition & Metabolism
Blood Chemistry & Metabolites
Mannose-6-Phosphate Levels. Evidence: 5/10. Source: PMID 39528825. Lower Levels.
Showing effects for A/G genotype
Mannose-6-Phosphate Levels. Evidence: 5/10. Source: PMID 39528825. Intermediate Levels.
Showing effects for G/G genotype
Metformin Response. Evidence: 5/10. Source: PMID 36853844. Stronger Response.
Sulfonylurea Side Effects. Evidence: 5/10. Source: PMID 39005567. Typical Risk.
Imatinib Response. Evidence: 5/10. Source: PMID 29427770. Higher Toxicity Risk.
Lamotrigine Metabolism. Evidence: 5/10. Source: PMID 27610747. Typical Metabolism.
Mannose-6-Phosphate Levels. Evidence: 5/10. Source: PMID 39528825. Higher Levels.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Carrying two copies of the A allele is associated with a less favorable response to several common medications. Clinical studies show that patients with this genotype undergoing metformin therapy for type 2 diabetes often experience poorer glycemic control and a higher rate of gastrointestinal side effects [1] [2]. Similarly, when treated with the leukemia drug imatinib, this genotype is linked to a suboptimal therapeutic response and lower rates of major molecular response [3] [4]. The transport of lamotrigine, an antiseizure medication, is also affected, resulting in slower drug metabolism and altered blood concentrations [5]. Furthermore, combination therapies involving sulfonylureas may carry an increased risk of gastrointestinal toxicity for individuals with this genetic profile [2]. These diverse pharmacogenomic effects suggest that standard drug dosages may not produce the expected therapeutic outcomes. Consequently, close clinical monitoring is highly beneficial when initiating these therapies. Understanding these genetic influences helps in the development of more personalized treatment strategies.
Poorer response to metformin; Suboptimal response to imatinib; Slower metabolism of lamotrigine; Increased risk of gastrointestinal side effects.
Sample genotype: AG (Heterozygous)
Carrying one copy of the A allele and one copy of the G allele is associated with altered transport of several widely used drugs. Research indicates that this heterozygous genotype may lead to a poorer glycemic response to metformin and a higher likelihood of gastrointestinal distress [1] [2]. In oncology, patients receiving imatinib for chronic myeloid leukemia show a lower rate of complete cytogenetic or molecular response compared to those with the major genotype [3] [4]. Slower metabolism of the epilepsy drug lamotrigine has also been observed, which can affect its therapeutic concentration in the body [5]. Additionally, the risk of gastrointestinal toxicity may be elevated when taking sulfonylureas [2]. These diverse pharmacogenomic effects suggest that standard drug dosages may not produce the expected therapeutic outcomes. Consequently, close clinical monitoring is highly beneficial when initiating these therapies. Understanding these genetic influences helps in the development of more personalized treatment strategies.
Sample genotype: GG (Homozygous)
Carrying two copies of the major G allele is generally associated with a highly favorable response to metformin therapy. Clinical trials demonstrate that individuals with this genotype achieve significantly better glycemic control and a greater reduction in HbA1c levels when treated with metformin [1] [2]. However, this genetic profile presents a trade-off when it comes to other medications. For patients treated with imatinib, the G/G genotype is linked to slower drug metabolism and an increased risk of drug-induced toxicity [3] [4]. On the positive side, these individuals typically maintain standard metabolism rates for lamotrigine and do not exhibit the elevated risk of gastrointestinal side effects seen with sulfonylureas in other genotypes [5]. These contrasting drug responses highlight how a single genetic variant can have opposite effects depending on the medication. Consequently, clinical monitoring remains important even when a positive response is expected for one drug. This knowledge allows for a more tailored approach to managing multiple health conditions.
Enhanced response to metformin; Slower metabolism of imatinib; Increased risk of imatinib toxicity; Typical lamotrigine metabolism.
Variants with shared genetic architecture
rs12208357 · SLC22A1 Gene · Chr 6 · Cholesterol and Drug Response
rs1564348 · SLC22A1 Gene · Chr 6 · Cholesterol Levels
rs34130495 · SLC22A1 Gene · Chr 6 · Medication Response
Content updated August 2026.
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