What you carry at this position in your DNA and what research says about it.
Metformin Response: 6/10 evidence, 12 publications.
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Sample genotype (not yours): A/A
Typical Response to Metformin and Parkinsons Medications
Standard transporter activity supports typical clinical responses to metformin and Parkinson's therapies.
What this genotype means: Typical response to metformin; Typical response to Parkinson's drugs.
Sample genotype (not yours): C/A
Reduced Response to Metformin and Parkinsons Medications
Carrying one copy of the C allele is linked to lower transporter activity, which may reduce the effectiveness of metformin and Parkinson's therapies.
What this genotype means: Suboptimal metformin response; Reduced response to Parkinson's drugs.
Sample genotype (not yours): C/C
Poorest Response to Metformin and Parkinsons Medications
Carrying two copies of the C allele significantly lowers transporter activity, leading to the lowest response rates for metformin and Parkinson's drugs.
What this genotype means: Lowest response rate to metformin; Weakest response to Parkinson's drugs.
Gene function and biological role
Gene Function: The SLC22A1 gene encodes the organic cation transporter 1 (OCT1), a protein primarily expressed in the liver and intestines [1]. OCT1 plays a critical role in the uptake and clearance of various clinically important drugs, including the first-line type 2 diabetes medication metformin [2]. It also transports several medications used to manage Parkinson's disease, such as amantadine and levodopa [3]. Variations in this gene can significantly alter the transporter's activity, leading to substantial differences in how people process and respond to these therapies [2] [3].
Variant Impact: The rs622342 variant is an intronic change located within the SLC22A1 gene that influences the expression and function of the OCT1 transporter [4]. The minor C allele is linked to reduced transporter activity, which impairs the cellular uptake of its drug substrates [4] [5]. This reduction in transport efficiency can lead to a decreased therapeutic response to metformin in patients with type 2 diabetes [4]. Furthermore, it is associated with altered clinical outcomes for several anti-Parkinsonian medications [3].
Key Insight: The same transporter that processes the common diabetes drug metformin also handles several major Parkinson's disease medications, linking their genetic response profiles.
Location: SLC22A1. Chromosome 6 · 6q25.3 · 160.2 Mb
Estimated prevalence by population
Global 9.7%; European 13.7%; African 3.6%; East Asian 2.5%; South Asian 6.4%; Americas 12.4%; Ashkenazi 6.0%; Finnish 10.7%; Middle Eastern 4.9%; Amish 3.6%.
Estimated CC genotype frequency.
Global 40.6%; European 46.6%; African 30.7%; East Asian 26.7%; South Asian 37.7%; Americas 45.7%; Ashkenazi 37.0%; Finnish 44.0%; Middle Eastern 34.4%; Amish 30.9%.
Estimated CA genotype frequency.
Global 49.7%; European 39.7%; African 65.8%; East Asian 70.8%; South Asian 55.9%; Americas 41.9%; Ashkenazi 57.0%; Finnish 45.3%; Middle Eastern 60.7%; Amish 65.5%.
Estimated AA genotype frequency.
Showing effects for A/A genotype
Pharmacogenomics
Diabetes Medication Response
Metformin Response. Evidence: 6/10. Source: PMID 25492374. Stronger Response.
Neurology & Mental Health
Neurodegenerative Diseases
Parkinson's Drug Response. Evidence: 5/10. Source: PMID 20680652. Typical Response.
Nutrition & Metabolism
Blood Chemistry & Metabolites
N-Acetyl-Isoputreanine Levels. Evidence: 4/10. Source: PMID 35050183. Lower Levels.
Showing effects for C/A genotype
Metformin Response. Evidence: 6/10. Source: PMID 25492374. Poorer Response.
Parkinson's Drug Response. Evidence: 5/10. Source: PMID 20680652. Poorer Response.
N-Acetyl-Isoputreanine Levels. Evidence: 4/10. Source: PMID 35050183. Intermediate Levels.
Showing effects for C/C genotype
N-Acetyl-Isoputreanine Levels. Evidence: 4/10. Source: PMID 35050183. Higher Levels.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Standard transporter function is maintained by this genotype, allowing for efficient cellular uptake of key medications [1]. Clinical studies demonstrate that patients with this genotype have a significantly higher likelihood of achieving optimal blood sugar control when treated with metformin monotherapy [2]. Specifically, research in South Indian populations showed a 5.6-fold greater chance of responding favorably to metformin compared to those with the CC genotype [2]. In the context of Parkinson's disease, this genotype is associated with a typical response to therapies like levodopa and amantadine [3]. Patients generally show a typical response, rather than the reduced response seen in C allele carriers [3]. Additionally, studies have linked this genotype to typical survival times following the initiation of levodopa therapy [3].
Typical response to metformin; Typical response to Parkinson's drugs.
Sample genotype: CA (Heterozygous)
Reduced transporter activity associated with this genotype can impair the cellular uptake of several common medications [1]. Patients with type 2 diabetes carrying this genotype often show a less pronounced reduction in blood sugar levels when taking metformin [2]. For individuals undergoing treatment for Parkinson's disease, this genotype is linked to a lower response to medications such as levodopa, amantadine, and selegiline [3]. Consequently, clinicians in the Rotterdam Study observed that patients with this genotype were prescribed higher daily doses of anti-Parkinsonian drugs [3]. The study also noted a shorter average survival time after starting levodopa therapy, potentially due to reduced drug bioavailability or transport to target tissues [3].
Suboptimal metformin response; Reduced response to Parkinson's drugs.
Sample genotype: CC (Homozygous)
Minimal transporter activity is characteristic of this genotype, which severely limits the cellular uptake of key therapeutic agents [1]. Type 2 diabetes patients with this genotype exhibit the lowest response rates to metformin monotherapy, often failing to reach glycemic targets [2]. In clinical trials, carriers of two C alleles had a significantly lower chance of responding to metformin compared to those with the AA genotype [2]. When managing Parkinson's disease, this genotype is associated with a markedly reduced response to levodopa, amantadine, and other dopaminergic therapies [3]. Data from the Rotterdam Study indicate that these patients respond substantially less strongly to anti-Parkinsonian medications [3]. Furthermore, the study identified a 1.47-fold higher mortality ratio after initiating levodopa therapy in patients carrying the C allele, highlighting the clinical impact of reduced transport [3].
Lowest response rate to metformin; Weakest response to Parkinson's drugs.
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
Clinical pharmacokinetics of metformin.
OCT1 polymorphism is associated with response and survival time in anti-Parkinsonian drug users.
Interaction between polymorphisms in the OCT1 and MATE1 transporter and metformin response.
Content updated September 2026.
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