ABCC2 rs3740065: What Your Genotype Means
The rs3740065 variant is a genetic polymorphism located in the ABCC2 gene, which encodes a protein responsible for transporting various substances across cell membranes. Research has explored its potential role in influencing how the body processes certain medications, though evidence regarding its clinical impact remains limited.
What each genotype means
Typical ABCC2 activity
This genotype represents the most common form of the ABCC2 promoter region. Research suggests this version of the gene is associated with standard transporter function, though individual responses to medications like methotrexate or tamoxifen can still vary based on other genetic and environmental factors. Please discuss any concerns regarding medication side effects or dosing with your clinician or pharmacist.
This is the most common genotype in most global populations, though frequencies vary by ancestry.
Intermediate ABCC2 variant
Carrying one copy of the T allele may influence the activity of the MRP2 transporter protein. Some studies suggest this variant is linked to altered risks for medication toxicity, such as hematologic side effects from high-dose methotrexate, while other research shows mixed or limited evidence for clinical impact. You should consult with your healthcare provider or pharmacist regarding your specific medication management and potential side effects.
This heterozygous genotype is common, appearing in a significant portion of European and East Asian populations.
Altered ABCC2 variant
This genotype, sometimes referred to as the -24T variant, has been associated in some studies with an increased risk of toxicity when taking certain medications like high-dose methotrexate. In specific clinical contexts, such as hormone receptor-positive breast cancer treatment with tamoxifen, this genotype has been linked to different recurrence-free survival outcomes in limited studies. Because evidence is mixed and context-dependent, please discuss your medication plan and any potential risks with your doctor or pharmacist.
This homozygous genotype is less common than the C/C or C/T genotypes, occurring in a smaller percentage of the population.
Understanding the rs3740065 Variant
The rs3740065 variant is a single nucleotide polymorphism (SNP) located within the ABCC2 gene on chromosome 10. In genetics, a SNP represents a variation at a single position in the DNA sequence among individuals. This specific variant is often studied in the context of pharmacogenomics, which examines how an individual's genetic makeup influences their response to drugs. Because it sits within a gene involved in cellular transport, researchers investigate whether this change in the DNA code alters the function or expression of the resulting protein. It is important to note that the presence of a specific genotype at this location does not guarantee a particular health outcome or drug response, as many factors—including other genes, environment, and lifestyle—contribute to how a person reacts to medical treatments.
The Role of the ABCC2 Gene
The ABCC2 gene provides instructions for making a protein known as multidrug resistance-associated protein 2 (MRP2). This protein acts as an 'export pump' found primarily in the liver, kidneys, and intestines. Its main job is to move various substances, including bile acids, toxins, and many pharmaceutical drugs, out of cells and into bile or urine for excretion. By facilitating the removal of these compounds, the MRP2 protein plays a critical role in protecting cells from the accumulation of potentially harmful substances. When the function of this transporter is altered, it can theoretically affect the bioavailability of medications, meaning the amount of a drug that reaches the bloodstream or the rate at which it is cleared from the body may change. Understanding this gene is essential for researchers studying why individuals may experience different side effects or therapeutic benefits from the same medication.
Research and Clinical Associations
Scientific studies have investigated whether the rs3740065 variant is linked to differences in how patients respond to specific therapies. For example, some research has explored its potential association with methotrexate toxicity and outcomes in patients receiving tamoxifen for breast cancer. However, the evidence supporting these links is currently considered limited. While some studies have observed statistical associations between the variant and clinical outcomes, these findings are not always consistent across different populations or study designs. Because the evidence is not definitive, this variant is not currently used as a standard clinical tool for guiding medication dosing. It is vital to understand that these associations are based on population-level data and cannot predict an individual's specific response. Any concerns regarding medication efficacy or side effects should always be discussed directly with a healthcare provider or pharmacist, who can provide guidance based on your full clinical history.
Population Frequency and Interpretation
The frequency of the rs3740065 variant varies across different ancestral groups. Data indicates that the minor allele frequency (MAF) is approximately 0.15 to 0.22 in European and East Asian populations. This means that a significant portion of the population carries at least one copy of the variant allele. When interpreting genetic information, it is helpful to remember that common variants are often part of normal human genetic diversity. Having a specific genotype is not inherently 'good' or 'bad'; rather, it is a piece of biological information that may or may not have clinical relevance depending on the context of the medication being used. Because the science in this area is still evolving, it is best to view this information as educational rather than diagnostic. Always consult with a medical professional before making any decisions about your health or treatment plans based on genetic test results.
How common is this variant?
The rs3740065 variant is relatively common, with a minor allele frequency of approximately 0.15 to 0.22 in European and East Asian populations.
Frequently asked questions
What does the ABCC2 gene do?
The ABCC2 gene produces the MRP2 protein, which acts as a pump to move drugs and toxins out of cells in the liver and kidneys. This process is essential for the body to clear medications and waste products effectively.
Can I use this genetic information to change my medication?
No. You should never change your medication or dosage based on genetic test results without consulting your doctor. Genetic associations are complex, and your clinician must consider your entire health profile before making any changes.
Is rs3740065 a diagnostic test for drug side effects?
No, rs3740065 is not a diagnostic test. While some research suggests it may be associated with drug response, the evidence is limited and not sufficient to predict how an individual will react to a specific medication.
Where can I find more information about my specific genotype?
You can discuss your genetic results with a genetic counselor or your primary care physician. They can help interpret the information in the context of your personal medical history and current treatments.
Sources & further reading
Educational information only, last refreshed 9/16/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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ABCC2 promoter variant (-24C>T) linked to altered biliary excretion and susceptibility to tenofovir- or methotrexate-induced nephrotoxicity/hepatotoxicity.
This variant is identified as pathogenic and associated with Dubin-Johnson syndrome.