What you carry at this position in your DNA and what research says about it.
NSAID Bleeding Risk: 5/10 evidence, 14 publications.
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Sample genotype (not yours): T/T
Typical Risk of NSAID-Related Bleeding
Standard liver enzyme activity allows for normal processing of common pain relievers and other medications. There is no elevated risk of gastrointestinal bleeding or nerve damage from specific drug therapies.
What this genotype means: Typical metabolism of NSAID pain relievers; Standard risk of paclitaxel-induced neuropathy; Normal clearance of certain diabetes medications.
Sample genotype (not yours): C/C
Significantly Higher Risk of NSAID-Related Bleeding
Significantly reduced enzyme activity slows the breakdown of common pain relievers, substantially increasing the risk of stomach bleeding. Chemotherapy and diabetes medications are also processed abnormally.
What this genotype means: Substantially higher risk of gastrointestinal bleeding with NSAIDs; Highly elevated risk of paclitaxel-induced neuropathy; Accelerated clearance of repaglinide and rosiglitazone.
Sample genotype (not yours): T/C
Increased Risk of NSAID-Related Bleeding
Altered liver enzyme activity leads to slower processing of certain pain relievers, raising the risk of stomach irritation. Some chemotherapy and diabetes medications may also be cleared differently.
What this genotype means: Elevated risk of gastrointestinal bleeding with NSAIDs; Higher risk of nerve pain during paclitaxel chemotherapy; Faster clearance of repaglinide and rosiglitazone.
Gene function and biological role
Gene Function: The CYP2C8 gene encodes a member of the cytochrome P450 superfamily of enzymes, which are major catalysts for drug metabolism in the liver [1]. This specific enzyme plays a critical role in processing clinical drugs, including nonsteroidal anti-inflammatory drugs, the chemotherapy agent paclitaxel, and certain diabetes medications [1] [2]. Variations in this gene can significantly alter how quickly these substances are cleared from the body [2]. When enzyme activity is reduced, drugs can accumulate to toxic levels, whereas increased activity can cause medications to be cleared too rapidly to be effective [2].
Variant Impact: This variant, rs10509681, is a missense mutation in the CYP2C8 gene that changes the amino acid lysine to arginine at position 399 of the protein, creating the CYP2C8*3 allele [1]. This structural change impairs the enzyme's ability to properly metabolize several common medications [1]. It is often inherited alongside variants in the neighboring CYP2C9 gene, compounding the impact on drug clearance [3]. The altered enzyme function is particularly relevant for individuals taking certain pain relievers or chemotherapy drugs [1] [4].
Key Insight: Carrying this variant can simultaneously increase the risk of side effects from some drugs while making other medications clear too quickly to work properly.
Location: CYP2C8. Chromosome 10 · 10q23.33 · 95.0 Mb
Estimated prevalence by population
Global 84.9%; European 78.5%; African 95.8%; East Asian 99.9%; South Asian 92.6%; Americas 82.4%; Ashkenazi 82.6%; Finnish 78.6%; Middle Eastern 71.1%; Amish 71.8%.
Estimated TT genotype frequency.
Global 14.3%; European 20.2%; African 4.1%; East Asian 0.1%; South Asian 7.3%; Americas 16.8%; Ashkenazi 16.6%; Finnish 20.1%; Middle Eastern 26.4%; Amish 25.8%.
Estimated TC 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 CC genotype frequency.
Showing effects for T/T genotype
Pharmacogenomics
Adverse Drug Reactions
NSAID Bleeding Risk. Evidence: 3/10. Source: PMID 18216720. Typical Risk.
Chemotherapy Response
Paclitaxel Neuropathy. Evidence: 5/10. Source: PMID 23413280. Typical Risk.
Diabetes Medication Response
Repaglinide Clearance. Evidence: 5/10. Source: PMID 14534525. Typical Clearance.
Rosiglitazone Clearance. Evidence: 5/10. Source: PMID 17178266. Typical Clearance.
Showing effects for C/C genotype
NSAID Bleeding Risk. Evidence: 3/10. Source: PMID 18216720. 1.8x Higher Risk.
Paclitaxel Neuropathy. Evidence: 5/10. Source: PMID 23413280. Increased Risk.
Repaglinide Clearance. Evidence: 5/10. Source: PMID 14534525. Faster Clearance.
Rosiglitazone Clearance. Evidence: 5/10. Source: PMID 17178266. Faster Clearance.
Showing effects for T/C genotype
NSAID Bleeding Risk. Evidence: 3/10. Source: PMID 18216720. Increased Risk.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Standard metabolic function is maintained by carrying two copies of the common T allele [1]. Common pain relievers like ibuprofen and naproxen are processed at a normal rate, keeping the risk of gastrointestinal bleeding at baseline levels [2]. Chemotherapy treatments using paclitaxel are also metabolized typically, without the elevated risk of nerve damage seen in variant carriers [3]. Diabetes medications like rosiglitazone and repaglinide remain in the bloodstream long enough to exert their intended therapeutic effects [4] [5]. Standard clinical dosing guidelines generally apply to this genotype because drug clearance rates are predictable [1]. No special precautions are typically indicated based on this genetic profile alone.
Typical metabolism of NSAID pain relievers; Standard risk of paclitaxel-induced neuropathy; Normal clearance of certain diabetes medications.
Sample genotype: CC (Homozygous)
Severely altered liver metabolism results from carrying two copies of the C variant allele [1]. Breakdown of nonsteroidal anti-inflammatory drugs is significantly impaired, leading to a nearly twofold increase in the risk of acute gastrointestinal bleeding [2]. This vulnerability is heightened further with alcohol consumption or when co-inherited with CYP2C9 variants [2]. Treatment with the chemotherapy drug paclitaxel carries a highly elevated risk of severe nerve damage and neuropathy [3]. Meanwhile, blood levels of the diabetes drugs repaglinide and rosiglitazone may drop too quickly due to accelerated clearance pathways [4] [5]. These combined pharmacogenomic effects make standard prescribing patterns less predictable and potentially riskier [1]. Alternative pain management strategies or adjusted therapeutic monitoring are often considered by clinicians for this profile.
Substantially higher risk of gastrointestinal bleeding with NSAIDs; Highly elevated risk of paclitaxel-induced neuropathy; Accelerated clearance of repaglinide and rosiglitazone.
Sample genotype: TC (Heterozygous)
Altered liver metabolism occurs due to carrying one copy of the C variant allele [1]. Processing of common pain relievers like ibuprofen is less efficient, which is associated with an elevated risk of acute gastrointestinal bleeding [2]. This risk can be further compounded if alcohol is consumed or if specific variants in the CYP2C9 gene are also present [2]. When undergoing chemotherapy with paclitaxel, there is an increased likelihood of developing painful peripheral neuropathy [3]. Conversely, certain diabetes medications like repaglinide and rosiglitazone may be cleared from the system more rapidly [4] [5]. These metabolic differences mean that standard drug doses might not behave as expected [1]. Discussing these potential sensitivities with a healthcare provider can help guide safer medication choices.
Elevated risk of gastrointestinal bleeding with NSAIDs; Higher risk of nerve pain during paclitaxel chemotherapy; Faster clearance of repaglinide and rosiglitazone.
Variants with shared genetic architecture
rs11572080 · CYP2C8 Gene · Chr 10 · Drug Response and Safety
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.
CYP2C8*3 increases risk of neuropathy in breast cancer patients treated with paclitaxel.
Pharmacokinetics and pharmacodynamics of rosiglitazone in relation to CYP2C8 genotype.
Polymorphism in CYP2C8 is associated with reduced plasma concentrations of repaglinide.
Content updated August 2026.
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