What you carry at this position in your DNA and what research says about it.
Cholesterol and Drug Response: 10/10 evidence, 25 publications.
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Sample genotype (not yours): C/C
Typical Cholesterol and Normal Drug Metabolism
This genotype is associated with fully functional OCT1 transporters and typical blood lipid levels. You are likely to respond normally to medications like metformin and have a standard risk of side effects from morphine.
What this genotype means: Typical blood lipid levels; Standard response to metformin; Normal risk of morphine side effects.
Sample genotype (not yours): C/T
Increased Cholesterol and Altered Drug Sensitivity
Carrying one copy of the T allele reduces OCT1 transporter function, which can elevate cholesterol levels. It also alters how your body processes certain medications, potentially increasing side effects from morphine or reducing metformin uptake.
What this genotype means: Elevated LDL and total cholesterol; Slower clearance of morphine; Reduced liver uptake of metformin.
Sample genotype (not yours): T/T
Elevated Cholesterol and Slower Drug Metabolism
Carrying two copies of the T allele causes a severe loss of OCT1 transporter function, leading to higher cholesterol levels. This genotype significantly slows the clearance of several medications, increasing the risk of side effects from morphine and reducing metformin uptake.
What this genotype means: Highest risk of elevated LDL cholesterol; Significantly slower morphine clearance; Impaired metformin uptake in liver.
Gene function and biological role
Gene Function: The SLC22A1 gene encodes the organic cation transporter 1 (OCT1), which is highly expressed in the liver. This transporter is crucial for the hepatic uptake of many therapeutic drugs, including metformin and morphine. By transporting these compounds into hepatocytes, OCT1 directly influences their systemic clearance and clinical efficacy. Genetic variations in this gene are a major source of inter-individual differences in drug response and side effects.
Variant Impact: The rs12208357 variant is a missense mutation that results in an arginine-to-cysteine substitution at position 61 (p.Arg61Cys) of the OCT1 protein. This change leads to a loss of transporter function, reducing the hepatic uptake of substrate drugs. Consequently, carriers of the T allele experience altered pharmacokinetics, such as slower clearance of morphine and reduced liver exposure to metformin. The variant is also associated with elevated levels of circulating lipids, including LDL and total cholesterol.
Key Insight: This variant acts like a biological gatekeeper, where carrying the T allele reduces the liver's ability to absorb and process several common medications, leading to unexpected drug sensitivities.
Location: SLC22A1. Chromosome 6 · 6q25.3 · 160.1 Mb
Estimated prevalence by population
Global 90.7%; European 85.5%; African 97.9%; East Asian 99.9%; South Asian 94.9%; Americas 94.6%; Ashkenazi 81.8%; Finnish 88.5%; Middle Eastern 83.7%; Amish 79.3%.
Estimated CC genotype frequency.
Global 9.0%; European 13.9%; African 2.1%; East Asian 0.1%; South Asian 5.0%; Americas 5.4%; Ashkenazi 17.2%; Finnish 11.1%; Middle Eastern 15.6%; Amish 19.5%.
Estimated CT genotype frequency.
Global 0.3%; European 0.6%; African < 0.1%; East Asian < 0.1%; South Asian 0.1%; Americas 0.1%; Ashkenazi 0.9%; Finnish 0.3%; Middle Eastern 0.7%; Amish 1.2%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Cardiovascular & Metabolic
Lipids & Cholesterol
LDL Cholesterol. Evidence: 10/10. Source: PMID 29507422. Typical.
Total Cholesterol. Evidence: 10/10. Source: PMID 25961943. Typical.
Pharmacogenomics
Diabetes Medication Response
Metformin Response. Evidence: 5/10. Source: PMID 28380657. Typical Response.
Pain Medication Response
Morphine Side Effects. Evidence: 6/10. Source: PMID 23859569. Typical Risk.
Tramadol Response. Evidence: 5/10. Source: PMID 27541716. Typical Response.
Organ Systems
Respiratory Health
Fenoterol Sensitivity. Evidence: 5/10. Source: PMID 28791698. Typical Sensitivity.
Showing effects for C/T genotype
LDL Cholesterol. Evidence: 10/10. Source: PMID 29507422. Increased.
Total Cholesterol. Evidence: 10/10. Source: PMID 25961943. Increased.
Metformin Response. Evidence: 5/10. Source: PMID 28380657. Slower Metabolism.
Morphine Side Effects. Evidence: 6/10. Source: PMID 23859569. Increased Risk.
Tramadol Response. Evidence: 5/10. Source: PMID 27541716. Higher Sensitivity.
Fenoterol Sensitivity. Evidence: 5/10. Source: PMID 28791698. Increased Side Effects.
Showing effects for T/T genotype
LDL Cholesterol. Evidence: 10/10. Source: PMID 29507422. Highest.
Total Cholesterol. Evidence: 10/10. Source: PMID 25961943. Highest.
Metformin Response. Evidence: 5/10. Source: PMID 28380657. Slowest Metabolism.
Morphine Side Effects. Evidence: 6/10. Source: PMID 23859569. Highest Risk.
Fenoterol Sensitivity. Evidence: 5/10. Source: PMID 28791698. Highest Side Effects.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Having two copies of the C allele means your body produces fully functional organic cation transporter 1 (OCT1) proteins. This allows for the normal uptake of various medications and metabolic compounds into liver cells. Consequently, you are likely to experience standard therapeutic responses to metformin, the first-line treatment for type 2 diabetes. Your risk of experiencing severe side effects, such as post-surgery nausea and vomiting from morphine, is typical because your liver clears the drug efficiently. Additionally, this genotype is associated with typical circulating levels of LDL and total cholesterol. You do not carry the loss-of-function variant that disrupts drug transport and elevates blood lipids.
Typical blood lipid levels; Standard response to metformin; Normal risk of morphine side effects.
Sample genotype: CT (Heterozygous)
Carrying one copy of the T allele leads to a partial loss of organic cation transporter 1 (OCT1) function in the liver. This reduction in transport capacity is linked to higher circulating levels of LDL and total cholesterol. Because the liver uptake of certain medications is reduced, you may experience altered drug pharmacokinetics. For instance, slower metabolism of morphine can increase your susceptibility to postoperative side effects like nausea and vomiting. Similarly, reduced hepatic uptake of metformin may influence how effectively the drug lowers blood sugar. You may also have increased sensitivity to other OCT1 substrates, such as fenoterol or sumatriptan, due to higher systemic exposure.
Elevated LDL and total cholesterol; Slower clearance of morphine; Reduced liver uptake of metformin.
Sample genotype: TT (Homozygous)
Having two copies of the T allele results in a profound loss of organic cation transporter 1 (OCT1) activity. Without functional transporters, the liver's ability to take up and process many common medications is severely compromised. This genotype is strongly associated with elevated levels of LDL and total cholesterol. When taking morphine, the lack of active transport leads to slower drug clearance and a significantly higher risk of postoperative nausea and vomiting. Metformin uptake into liver cells is also reduced, which can impair its glucose-lowering efficacy. Furthermore, you may experience heightened sensitivity or adverse reactions to other drugs processed by OCT1, such as fenoterol and sumatriptan.
Highest risk of elevated LDL cholesterol; Significantly slower morphine clearance; Impaired metformin uptake in liver.
Variants with shared genetic architecture
rs1564348 · SLC22A1 Gene · Chr 6 · Cholesterol Levels
rs34130495 · SLC22A1 Gene · Chr 6 · Medication Response
rs2297374 · SLC22A1 Gene · Chr 6 · Cholesterol Levels
Content updated August 2026.
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