What you carry at this position in your DNA and what research says about it.
Statin Muscle Pain Risk: 5/10 evidence, 32 publications.
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Sample genotype (not yours): A/A
Higher Risk of Statin-Induced Muscle Pain
Inheriting two copies of the reference A allele is linked to a higher risk of muscle pain and elevated creatine kinase levels when taking statins. This genotype may also affect how the body processes other medications.
What this genotype means: Higher risk of statin-induced muscle pain; Increased likelihood of enalapril-induced cough; Lower risk of methotrexate toxicity.
Sample genotype (not yours): A/G
Reduced Risk of Statin-Induced Muscle Pain
Having a single copy of the G allele is associated with a lower risk of statin-induced muscle pain and side effects. It represents an intermediate drug-clearance profile for several medications.
What this genotype means: Lower risk of statin-induced muscle pain; Intermediate clearance of methotrexate; Better response to irinotecan chemotherapy.
Sample genotype (not yours): G/G
Lower Statin Muscle Risk but Higher Chemotherapy Toxicity
Possessing two copies of the G allele offers excellent protection against statin-induced muscle pain but increases the risk of toxicity from certain chemotherapy drugs. This genotype represents a highly active transporter state.
What this genotype means: Lowest risk of statin-induced muscle pain; Higher risk of methotrexate-induced liver and kidney damage; Increased risk of neutropenia from irinotecan.
Gene function and biological role
Gene Function: The SLCO1B1 gene encodes the organic anion-transporting polypeptide 1B1 (OATP1B1), a crucial transporter protein primarily located in the liver [1]. This transporter facilitates the hepatic uptake of various endogenous compounds, such as bilirubin, as well as numerous widely prescribed medications [1] [2]. Among these drugs are HMG-CoA reductase inhibitors, commonly known as statins, which lower cholesterol [2]. OATP1B1 also transports other therapeutic agents, including the immunosuppressant methotrexate and the cancer drug irinotecan [3] [4]. Genetic variations that alter the expression or function of this transporter can significantly impact drug clearance, leading to altered efficacy or an increased risk of adverse drug reactions [2] [3].
Variant Impact: A single nucleotide substitution at rs2306283 represents an adenine-to-guanine (A>G) change in the SLCO1B1 gene, resulting in an asparagine-to-aspartate amino acid change at position 130 (p.Asn130Asp) [5]. Often referred to as the *1B allele, this genetic change is widely studied for its influence on the functional activity of the OATP1B1 transporter [5] [6]. Unlike some loss-of-function variants in the same gene, this specific alteration is generally associated with increased transporter activity for certain substrates [6]. Consequently, it can enhance the liver's uptake of medications like statins, thereby reducing their systemic circulation and lowering the risk of muscle-related side effects [6] [7]. However, its effects are highly substrate-dependent, and it may conversely increase systemic exposure or toxicity risks for other drugs, such as methotrexate [8].
Key Insight: While this variant helps protect against muscle pain from cholesterol-lowering statins, it simultaneously increases the risk of severe side effects from certain chemotherapy drugs.
Location: SLCO1B1. Chromosome 12 · 12p12.1 · 21.2 Mb
Estimated prevalence by population
Global 24.5%; European 35.8%; African 5.4%; East Asian 6.5%; South Asian 23.4%; Americas 28.1%; Ashkenazi 29.3%; Finnish 29.7%; Middle Eastern 26.7%; Amish 10.1%.
Estimated AA genotype frequency.
Global 44.7%; European 48.1%; African 35.6%; East Asian 37.9%; South Asian 49.9%; Americas 49.8%; Ashkenazi 49.7%; Finnish 49.6%; Middle Eastern 49.9%; Amish 43.3%.
Estimated AG genotype frequency.
Global 30.9%; European 16.1%; African 59.0%; East Asian 55.6%; South Asian 26.6%; Americas 22.1%; Ashkenazi 21.1%; Finnish 20.7%; Middle Eastern 23.3%; Amish 46.6%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Pharmacogenomics
Adverse Drug Reactions
Statin Muscle Pain. Evidence: 5/10. Source: PMID 24595600. Increased Risk.
Immunosuppressant & Biologic Response
Methotrexate Toxicity. Evidence: 6/10. Source: PMID 33501733. Typical Risk.
Chemotherapy Response
Irinotecan Toxicity. Evidence: 5/10. Source: PMID 24143213. Typical Risk.
Anticoagulant & Blood Thinner Response
Edoxaban Bleeding Risk. Evidence: 5/10. Source: PMID 37749323. Typical Risk.
Showing effects for A/G genotype
Statin Muscle Pain. Evidence: 5/10. Source: PMID 24595600. Reduced Risk.
Methotrexate Toxicity. Evidence: 6/10. Source: PMID 33501733. Slightly Higher Risk.
Showing effects for G/G genotype
Statin Muscle Pain. Evidence: 5/10. Source: PMID 24595600. Lowest Risk.
Methotrexate Toxicity. Evidence: 6/10. Source: PMID 33501733. Increased Risk.
Irinotecan Toxicity. Evidence: 5/10. Source: PMID 24143213. Increased Risk.
Edoxaban Bleeding Risk. Evidence: 5/10. Source: PMID 37749323. Reduced Risk.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Inheriting two copies of the reference A allele typically results in standard OATP1B1 transporter activity, which is lower than the activity associated with the G variant [1]. When taking HMG-CoA reductase inhibitors (statins), this lower uptake rate can lead to higher systemic levels of the drug in the bloodstream [1] [2]. Consequently, there is an increased likelihood of experiencing elevated creatine kinase levels, a key marker of muscle damage and statin-induced myopathy [3]. On the other hand, this genotype is generally associated with a lower risk of toxicity from chemotherapy agents like methotrexate compared to those carrying the G allele [4]. It is also linked to a higher likelihood of developing a dry cough when taking the blood pressure medication enalapril [5]. Understanding these drug-response patterns can help healthcare providers select the most appropriate medications and dosages.
Higher risk of statin-induced muscle pain; Increased likelihood of enalapril-induced cough; Lower risk of methotrexate toxicity.
Sample genotype: AG (Heterozygous)
Possessing one copy of the G allele results in moderately increased OATP1B1 transporter activity, which enhances the liver's ability to clear certain drugs from the bloodstream [1]. This increased clearance is particularly beneficial for individuals taking statins, as it lowers systemic drug exposure and reduces the risk of muscle-related side effects [2]. However, because this genotype represents an intermediate state, the response to other medications can vary [3]. For instance, some studies suggest a slightly higher risk of mild gastrointestinal or liver toxicity when undergoing high-dose methotrexate therapy compared to the A/A genotype [3] [4]. It is also associated with a better response to the chemotherapy drug irinotecan and a lower likelihood of irinotecan-induced toxicity [5]. Overall, this genotype provides a protective buffer against statin-induced muscle issues while maintaining a relatively balanced profile for other therapies.
Lower risk of statin-induced muscle pain; Intermediate clearance of methotrexate; Better response to irinotecan chemotherapy.
Sample genotype: GG (Homozygous)
Possessing two copies of the G allele, also known as the *1B/*1B genotype, results in significantly increased OATP1B1 transporter activity [1]. This highly active state rapidly clears statins from the bloodstream into the liver, resulting in a lower risk of statin-induced muscle pain and elevated creatine kinase [2]. It is also associated with a reduced likelihood of bleeding complications when taking the anticoagulant edoxaban [3]. However, this rapid transport can be problematic for other medications, particularly chemotherapy agents [4]. Individuals with this genotype have a significantly higher risk of experiencing severe toxicities, including gastrointestinal distress, liver damage, and kidney injury, when treated with methotrexate [4] [5]. There is also an increased risk of neutropenia, a severe drop in white blood cells, during irinotecan chemotherapy [6]. These distinct drug-response profiles highlight the importance of personalized medicine when selecting therapeutic regimens.
Lowest risk of statin-induced muscle pain; Higher risk of methotrexate-induced liver and kidney damage; Increased risk of neutropenia from irinotecan.
Variants with shared genetic architecture
rs4149056 · SLCO1B1 Gene · Chr 12 · Statin Side Effect Risk
rs11045819 · SLCO1B1 Gene · Chr 12 · Statin Response
rs4149081 · SLCO1B1 Gene · Chr 12 · Statin Response
Genome-wide study of methotrexate clearance replicates SLCO1B1.
Content updated August 2026.
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