What you carry at this position in your DNA and what research says about it.
Drug Response and Safety: 5/10 evidence, 15 publications.
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Sample genotype (not yours): C/C
Typical Drug Metabolism and Standard NSAID Safety
Standard enzyme activity ensures normal processing of common medications. There is no elevated risk of gastrointestinal bleeding when taking NSAIDs.
What this genotype means: Typical clearance of common medications; Standard risk profile for NSAID-related side effects.
Sample genotype (not yours): C/T
Altered Drug Clearance and Increased NSAID Bleeding Risk
Carrying one copy of the variant allele alters the metabolism of several medications. This change increases the risk of gastrointestinal bleeding from NSAIDs but is associated with improved asthma control.
What this genotype means: Altered metabolism of specific prescription drugs; Elevated risk of gastrointestinal side effects from NSAIDs.
Sample genotype (not yours): T/T
Significantly Altered Drug Metabolism and Higher Side Effect Risk
Two copies of the variant allele significantly accelerate or impair the clearance of specific drugs. This genotype is linked to a higher risk of NSAID-related bleeding and paclitaxel-induced nerve damage.
What this genotype means: Significantly altered clearance of several medications; Elevated risk of nerve damage from paclitaxel chemotherapy.
Gene function and biological role
Gene Function: The CYP2C8 gene encodes a member of the cytochrome P450 superfamily of enzymes, which are primarily responsible for metabolizing clinically important drugs and endogenous compounds [1]. Located on chromosome 10, this enzyme is highly expressed in the liver, where it plays a key role in processing various medications, including nonsteroidal anti-inflammatory drugs (NSAIDs), the anti-diabetic drug repaglinide, and the chemotherapy agent paclitaxel [1] [2]. Beyond drug clearance, the enzyme is involved in the metabolism of arachidonic acid and other polyunsaturated fatty acids, which are critical mediators of inflammation and vascular tone [3]. Genetic variations in this gene can significantly alter enzyme activity, leading to substantial differences in drug efficacy, side effects, and inflammatory responses [1] [3].
Variant Impact: The rs11572080 variant, also known as the CYP2C8*3 allele, is a missense mutation that changes the amino acid arginine to lysine at position 139 of the CYP2C8 protein [3]. This structural alteration significantly impacts the enzyme's metabolic capacity in a substrate-dependent manner, accelerating the clearance of some drugs while impairing the breakdown of others [2]. It is in near-perfect linkage disequilibrium with another functional variant, meaning they are almost always inherited together [3]. The variant is relatively common in European populations but is rare in individuals of East Asian and African descent [3].
Key Insight: This variant alters drug clearance in opposite directions depending on the medication, accelerating the metabolism of some drugs while slowing down others.
Location: CYP2C8. Chromosome 10 · 10q23.33 · 95.1 Mb
Origin Story: This variant is part of a 300-kilobase haplotype on chromosome 10 that was inherited from Neandertals, specifically matching sequences found in Neandertal remains from the Chagyrskaya Cave in Siberia.
Estimated prevalence by population
Global 84.9%; European 78.5%; African 95.8%; East Asian 99.9%; South Asian 92.5%; Americas 82.4%; Ashkenazi 82.6%; Finnish 78.6%; Middle Eastern 71.1%; Amish 71.8%.
Estimated CC genotype frequency.
Global 14.3%; European 20.2%; African 4.1%; East Asian 0.1%; South Asian 7.3%; Americas 16.7%; Ashkenazi 16.6%; Finnish 20.2%; Middle Eastern 26.4%; Amish 25.8%.
Estimated CT genotype frequency.
Global 0.8%; European 1.3%; African < 0.1%; East Asian < 0.1%; South Asian 0.1%; Americas 0.9%; Ashkenazi 0.8%; Finnish 1.3%; Middle Eastern 2.4%; Amish 2.3%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Pharmacogenomics
Adverse Drug Reactions
NSAID Bleeding Risk. Evidence: 3/10. Source: PMID 18216720. Typical Risk.
Chemotherapy Response
Paclitaxel Toxicity. Evidence: 5/10. Source: PMID 20212519. Typical Risk.
Diabetes Medication Response
Repaglinide Clearance. Evidence: 5/10. Source: PMID 14534525. Typical Metabolism.
Organ Systems
Respiratory Health
Asthma Control. Evidence: 5/10. Source: PMID 38772712. Typical Control.
Showing effects for C/T genotype
NSAID Bleeding Risk. Evidence: 3/10. Source: PMID 18216720. ~1.8x Higher Risk.
Repaglinide Clearance. Evidence: 5/10. Source: PMID 14534525. Faster Metabolism.
Asthma Control. Evidence: 5/10. Source: PMID 38772712. Improved Control.
Showing effects for T/T genotype
NSAID Bleeding Risk. Evidence: 3/10. Source: PMID 18216720. Elevated Risk.
Paclitaxel Toxicity. Evidence: 5/10. Source: PMID 20212519. Increased Risk.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Standard enzyme activity is maintained with two copies of the reference allele, ensuring typical clearance rates for several common prescription and over-the-counter medications [1]. When using nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, there is no genetically elevated risk of developing acute gastrointestinal bleeding [2]. Similarly, standard clearance of the chemotherapy drug paclitaxel helps maintain a typical risk profile for treatment-related nerve damage [3]. For individuals managing type 2 diabetes, medications like repaglinide are metabolized at expected rates, supporting predictable blood sugar responses [4]. However, this genotype does not carry the genetic advantage for pediatric asthma symptom control observed with the variant allele [5].
Typical clearance of common medications; Standard risk profile for NSAID-related side effects.
Sample genotype: CT (Heterozygous)
Carrying one copy of the variant allele alters the metabolic rate of several therapeutic agents, leading to substrate-dependent clinical effects [1]. When taking certain NSAIDs, there is an estimated 1.81-fold higher risk of developing acute gastrointestinal bleeding, which further increases with alcohol consumption [2]. Conversely, children with this genotype may experience improved asthma symptom control, potentially due to altered lipid mediator production and reduced airway inflammation [3]. The variant also leads to faster clearance of the diabetes medication repaglinide, which can lower its plasma concentration and modify its therapeutic effect [4]. Healthcare providers often consider these metabolic differences when selecting drug classes or adjusting dosages to optimize safety and efficacy [1].
Altered metabolism of specific prescription drugs; Elevated risk of gastrointestinal side effects from NSAIDs.
Sample genotype: TT (Homozygous)
Carrying two copies of the variant allele leads to the most pronounced changes in CYP2C8 enzyme activity, significantly affecting drug safety and efficacy [1]. The risk of experiencing acute gastrointestinal bleeding when using common NSAIDs is substantially elevated compared to the standard genotype [2]. Additionally, patients undergoing chemotherapy with paclitaxel face a significantly increased risk of developing treatment-limiting neurotoxicity, such as numbness or tingling in the extremities [3]. On the therapeutic side, this genotype is associated with faster metabolism of the diabetes drug repaglinide, which may reduce its overall efficacy [4]. However, it also correlates with improved asthma symptom control in pediatric populations, highlighting the complex, substrate-specific nature of this genetic variant [5].
Significantly altered clearance of several medications; Elevated risk of nerve damage from paclitaxel chemotherapy.
Variants with shared genetic architecture
rs10509681 · CYP2C8 Gene · Chr 10 · NSAID Bleeding Risk
rs1058930 · CYP2C8 Gene · Chr 10 · Medication Clearance Rate
rs1934951 · CYP2C8 Gene · Chr 10 · Jaw Bone Damage Risk
Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies.
Polymorphism in CYP2C8 is associated with reduced plasma concentrations of repaglinide.
Polymorphisms in cytochromes P450 2C8 and 3A5 are associated with paclitaxel neurotoxicity.
Content updated August 2026.
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