CES1 rs8192935: Dabigatran Pharmacogenomics Explained
The rs8192935 variant is a polymorphism in the CES1 gene, which encodes an enzyme responsible for activating the anticoagulant medication dabigatran. Research has investigated its association with variations in drug trough and peak concentrations in patients.
What each genotype means
Lower dabigatran peak levels
This genotype is associated with lower peak plasma concentrations of the anticoagulant dabigatran compared to those with the GG genotype. Research indicates that this variant may influence how your body processes this specific medication. Please discuss your medication dosing and monitoring with your clinician or pharmacist.
Reported in various clinical cohorts including Chinese subjects.
Intermediate dabigatran peak levels
This heterozygous genotype is associated with intermediate peak plasma concentrations of dabigatran. The clinical significance of this variation can be influenced by other factors, including kidney function and other genetic markers. Please discuss your medication dosing and monitoring with your clinician or pharmacist.
Reported in various clinical cohorts including Chinese subjects.
Higher dabigatran peak levels
This genotype is associated with increased peak plasma concentrations of the anticoagulant dabigatran. While this is a statistical association observed in clinical studies, individual responses to medication can vary significantly. Please discuss your medication dosing and monitoring with your clinician or pharmacist.
Reported in various clinical cohorts including Chinese subjects.
What is the rs8192935 Variant?
The rs8192935 variant is a single nucleotide polymorphism (SNP) located within the CES1 gene. This gene provides instructions for making the carboxylesterase 1 enzyme, which is primarily found in the liver. In the field of pharmacogenomics, researchers study this variant because it may influence how the body processes certain medications. Specifically, rs8192935 is located in a region that can affect the expression or function of the CES1 enzyme. Because enzymes are the "machinery" that breaks down or activates drugs, changes in their genetic code can lead to differences in how quickly or effectively a medication is processed. This makes rs8192935 a subject of interest for understanding why patients might experience different drug levels while taking the same dose of a medication.
The Role of the CES1 Gene
The CES1 gene is essential for the metabolism of various drugs, including the prodrug dabigatran etexilate. Dabigatran etexilate is an anticoagulant used to prevent blood clots; however, it must be converted into its active form, dabigatran, by the carboxylesterase 1 enzyme in the liver. If the CES1 enzyme is less efficient due to genetic variations, the conversion process may be altered, potentially leading to different concentrations of the active drug in the bloodstream. Because the balance between preventing clots and avoiding bleeding is delicate, understanding how CES1 variants influence drug levels is a key area of clinical research. The gene's function is highly specific to the liver, making it a critical component of the body's overall drug-processing system.
Research Associations and Evidence Strength
The evidence linking rs8192935 to dabigatran pharmacokinetics is considered moderate. Several studies have investigated whether this variant influences the trough (lowest) or peak (highest) concentrations of dabigatran in the blood. Some research has observed that carriers of different genotypes may exhibit variations in these drug levels. However, the results across different studies have been inconsistent, with some finding significant associations and others finding no clear impact on clinical outcomes like bleeding or stroke. Because of this heterogeneity and the limited sample sizes in many clinical cohorts, current evidence is not sufficient to support genotype-guided dosing in routine clinical practice. It remains an area of active investigation, and patients should always follow the dosing instructions provided by their healthcare team.
Population Frequency
The rs8192935 variant has been reported in various clinical cohorts, including studies involving Chinese subjects and other multiethnic populations. The frequency of the alleles can differ significantly depending on the ancestral background of the group being studied. Because it is a known polymorphism, it is present in a notable percentage of the population, though it is not necessarily the most common variant at this locus. Researchers continue to collect data from diverse groups to better understand how the prevalence of this variant might contribute to observed differences in drug response across different global populations.
Clinical Considerations and Next Steps
It is vital to understand that genetic variants like rs8192935 are only one piece of a very complex puzzle. Factors such as kidney function (creatinine clearance), age, sex, and other medications play a much larger role in determining how your body processes anticoagulants. You should never use genetic test results to adjust your medication dosage or stop taking your prescribed treatment. If you are curious about how your genetics might influence your response to a medication, the best course of action is to discuss this with your doctor or a clinical pharmacist. They are trained to interpret clinical data and can ensure that your treatment plan is safe and effective based on established medical guidelines, rather than individual genetic markers alone.
How common is this variant?
This variant is reported in various clinical cohorts, including Chinese subjects, with frequencies that vary across different ancestral groups.
Frequently asked questions
Should I get tested for rs8192935 before taking dabigatran?
No. Current medical guidelines do not recommend routine genetic testing for this variant before starting dabigatran. Dosing is determined by clinical factors like kidney function and weight.
Does this variant mean I will have a bleeding event?
No. While some studies look at associations with drug levels, there is no consistent evidence that this variant alone predicts bleeding risk. Always monitor for symptoms and follow your doctor's advice.
Can I change my dose based on my genotype?
Absolutely not. Changing your medication dose without medical supervision can be dangerous. Always consult your prescribing physician before making any changes to your treatment.
Why do studies show different results for this SNP?
Pharmacogenomic studies are complex and can be influenced by differences in study design, patient demographics, and other genetic factors. This is why the evidence is currently considered moderate and not yet ready for clinical use.
Sources & further reading
Educational information only, last refreshed 11/7/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Missense variant in CES1 (G143E) that significantly reduces carboxylesterase 1 enzymatic activity, impacting drug metabolism.
Intronic regulatory variant in CES1 linked to hepatic ester hydrolysis and lipid metabolite levels.