What you carry at this position in your DNA and what research says about it.
Statin Response: 8/10 evidence, 11 publications.
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Sample genotype (not yours): G/G
Typical Statin Response and Normal Drug Clearance
This genotype is associated with standard liver transporter activity, leading to typical clearance of medications like statins and methotrexate. It represents the baseline genetic profile for these drug pathways.
What this genotype means: Typical response to cholesterol-lowering statins; Standard clearance rate for methotrexate; Baseline levels of bilirubin and triglycerides.
Sample genotype (not yours): A/A
Enhanced Statin Response but Slower Drug Clearance
Carrying two copies of the A allele is associated with a highly effective cholesterol-lowering response to statins, but also significantly slower clearance of other medications. This profile requires careful consideration when prescribing sensitive drugs.
What this genotype means: Highly pronounced reduction in LDL cholesterol from statins; Significantly slower clearance of methotrexate; Elevated baseline bilirubin and triglycerides.
Sample genotype (not yours): G/A
Carrying one copy of the A allele is linked to a more pronounced cholesterol reduction when taking statins, alongside slower clearance of certain medications. This creates a unique trade-off between cardiovascular benefits and drug sensitivity.
What this genotype means: Greater reduction in LDL cholesterol from statins; Slower clearance of methotrexate; Slightly elevated baseline bilirubin and triglycerides.
Gene function and biological role
Gene Function: The SLCO1B1 gene encodes a critical transport protein called organic anion transporting polypeptide 1B1, or OATP1B1. This transporter is primarily located in the liver, where it helps clear compounds from the blood into liver cells for processing and elimination. Among its key targets are various medications, including cholesterol-lowering statins and the chemotherapy drug methotrexate. It also plays a natural role in transporting endogenous substances like bilirubin and thyroid hormones. Variations in this gene can significantly alter how efficiently the liver processes these compounds, directly impacting drug efficacy and the risk of side effects.
Variant Impact: The rs4149081 variant is an intronic change located within the SLCO1B1 gene. Although it does not directly alter the amino acid sequence of the transporter protein, it is in strong linkage disequilibrium with other functional variants that affect transporter activity. This genetic marker is closely linked to differences in how the body processes common medications and clears metabolic waste. Studies have demonstrated that the presence of the A allele at this locus correlates with altered clearance rates for therapeutic drugs like methotrexate. Additionally, this variant is associated with subtle variations in systemic lipid levels and bilirubin clearance.
Key Insight: A single genetic change can make you more sensitive to cholesterol-lowering statins while simultaneously slowing down how your liver clears other common medications.
Location: SLCO1B1. Chromosome 12 · 12p12.1 · 21.2 Mb
Estimated prevalence by population
Global 66.8%; European 68.7%; African 70.8%; East Asian 30.1%; South Asian 83.0%; Americas 67.3%; Ashkenazi 68.6%; Finnish 45.7%; Middle Eastern 64.2%; Amish 87.0%.
Estimated GG genotype frequency.
Global 29.4%; European 28.4%; African 26.7%; East Asian 49.5%; South Asian 16.2%; Americas 29.5%; Ashkenazi 28.5%; Finnish 43.8%; Middle Eastern 31.8%; Amish 12.5%.
Estimated GA genotype frequency.
Global 3.9%; European 2.9%; African 2.5%; East Asian 20.3%; South Asian 0.8%; Americas 3.2%; Ashkenazi 3.0%; Finnish 10.5%; Middle Eastern 3.9%; Amish 0.5%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Pharmacogenomics
Lipid-Lowering Drug Response
Statin Response. Evidence: 3/10. Source: PMID 22668755. Typical Response.
Immunosuppressant & Biologic Response
Methotrexate Clearance. Evidence: 5/10. Source: PMID 19901119. Normal Clearance.
Organ Systems
Liver Function & Disease
Bilirubin Levels. Evidence: 8/10. Source: PMID 27897004. Typical Levels.
Cardiovascular & Metabolic
Lipids & Cholesterol
Triglycerides. Evidence: 8/10. Source: PMID 33462484. Typical Levels.
Showing effects for A/A genotype
Statin Response. Evidence: 3/10. Source: PMID 22668755. Enhanced Response.
Methotrexate Clearance. Evidence: 5/10. Source: PMID 19901119. Slower Clearance.
Bilirubin Levels. Evidence: 8/10. Source: PMID 27897004. Higher Levels.
Triglycerides. Evidence: 8/10. Source: PMID 33462484. Higher Levels.
Showing effects for G/A genotype
Bilirubin Levels. Evidence: 8/10. Source: PMID 27897004. Slightly Higher.
Triglycerides. Evidence: 8/10. Source: PMID 33462484. Slightly Higher.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Standard liver transporter function is maintained with two copies of the common G allele. This ensures that medications like methotrexate are cleared from the bloodstream at a typical rate, reducing the risk of drug-related toxicity during treatment. For individuals taking cholesterol-lowering statins, this genotype is associated with a standard reduction in low-density lipoprotein cholesterol. Natural metabolic processes, such as the clearance of bilirubin, also function at baseline levels. Because drug clearance is normal, standard dosing guidelines for sensitive medications generally apply. This profile represents the most common genetic pattern globally, providing a reliable baseline for cardiovascular and metabolic health.
Typical response to cholesterol-lowering statins; Standard clearance rate for methotrexate; Baseline levels of bilirubin and triglycerides.
Sample genotype: AA (Homozygous)
Transporter activity in the liver is significantly modified by the presence of two A alleles. Individuals with this genotype often experience a highly pronounced reduction in low-density lipoprotein cholesterol when treated with statins. Conversely, the clearance of the chemotherapy agent methotrexate is significantly delayed, leading to prolonged exposure in the bloodstream. This delayed clearance is a known risk factor for elevated drug concentrations and associated toxicities. Metabolic profiles may also show higher baseline levels of bilirubin and triglycerides due to altered transport dynamics. Understanding these patterns helps explain individual differences in medication tolerance and efficacy.
Highly pronounced reduction in LDL cholesterol from statins; Significantly slower clearance of methotrexate; Elevated baseline bilirubin and triglycerides.
Sample genotype: GA (Heterozygous)
Having one copy of the A allele alters the efficiency of the OATP1B1 liver transporter. Clinical studies show that this genetic profile is associated with a greater reduction in low-density lipoprotein cholesterol when using statins like simvastatin or rosuvastatin. However, this same change slows down the liver's ability to clear other medications, such as the chemotherapy drug methotrexate. Slower clearance can lead to higher circulating levels of the drug, potentially increasing the risk of side effects like gastrointestinal toxicity. On a metabolic level, this genotype is also linked to slightly higher baseline levels of bilirubin and triglycerides. These diverse effects highlight how a single genetic change can produce contrasting outcomes depending on the specific substance being processed.
Greater reduction in LDL cholesterol from statins; Slower clearance of methotrexate; Slightly elevated baseline bilirubin and triglycerides.
Variants with shared genetic architecture
rs4149056 · SLCO1B1 Gene · Chr 12 · Statin Side Effect Risk
rs11045819 · SLCO1B1 Gene · Chr 12 · Statin Response
rs11045879 · SLCO1B1 Gene · Chr 12 · Chemotherapy Toxicity Risk
Content updated August 2026.
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