NAT2 rs3745275: What Your Genotype Means
The rs3745275 variant is a specific change in the NAT2 gene, which provides instructions for an enzyme responsible for processing various drugs and environmental substances. Research associates this variant with the slow acetylator phenotype, which can influence how efficiently an individual metabolizes medications like isoniazid and hydralazine.
What each genotype means
Potential slow acetylator status
This genotype is associated with the slow acetylator phenotype in the NAT2 gene, which may lead to slower metabolism of certain medications like isoniazid. Individuals with this profile may have a higher risk of experiencing adverse reactions to these drugs due to increased blood concentrations. Please discuss your medication dosing and any potential side effects with your clinician or pharmacist.
The frequency of this genotype varies significantly by ancestry, occurring in approximately 9% of the total population in diverse US cohorts.
Intermediate acetylator status
This genotype represents an intermediate status for the NAT2 enzyme, which is responsible for metabolizing specific drugs like isoniazid. Research indicates that individuals with this profile typically exhibit metabolic activity between that of rapid and slow acetylators. You should consult your healthcare provider or pharmacist regarding how this may influence your response to specific medications.
This is a common genotype, observed in approximately 43% of the total population across diverse ancestry groups.
Likely rapid acetylator status
This genotype is associated with the rapid acetylator phenotype, which generally results in faster clearance of drugs metabolized by the NAT2 enzyme. While this is a normal metabolic variation, it may influence the effectiveness of certain treatments that require specific blood concentration levels. Always consult your clinician or pharmacist to determine if your genotype is relevant to your current medication regimen.
This is the most frequent genotype, found in approximately 48% of the total population across diverse ancestry groups.
What Is the rs3745275 Variant?
Genetic variants are natural differences in our DNA sequences. The rs3745275 variant is located within the NAT2 (N-acetyltransferase 2) gene, situated on chromosome 8. NAT2 is a highly polymorphic gene, meaning it contains many common variations that differ between people. These variations, including rs3745275, act as instructions that can alter the production or function of the NAT2 enzyme. Because this enzyme is responsible for chemically modifying (acetylating) certain compounds, changes in the gene can shift an individual’s metabolic rate, categorizing them as a fast, intermediate, or slow acetylator. These categories are not diseases; rather, they describe the pace at which your body processes specific substances.
The Role of the NAT2 Gene
The NAT2 gene encodes an enzyme primarily active in the liver and intestines. Its main function is to perform a phase II detoxification reaction called acetylation, where it adds an acetyl group to various molecules. This process can either deactivate certain drugs—making them easier to excrete—or, in some cases, activate them. By controlling the speed of this reaction, NAT2 directly influences the concentration of these substances in your bloodstream. When the enzyme works more slowly, drug levels may remain higher for longer, potentially increasing the risk of side effects, whereas faster processing might lead to lower drug exposure.
Research and Associations
Scientific evidence links NAT2 variations to how individuals respond to specific medications and environmental factors. For example, isoniazid (used for tuberculosis) and hydralazine (used for hypertension) are metabolized by NAT2. Research suggests that slow acetylators may have an increased risk of adverse reactions to these drugs because their bodies take longer to break them down. Additionally, epidemiological studies have explored links between slow acetylator status and a higher risk of bladder cancer, particularly in individuals with high exposure to aromatic amines from tobacco smoke or certain industrial environments. It is important to note that these are population-level associations. Individual outcomes are influenced by a complex mix of genetics, dosage, overall health, and environmental exposures.
Managing Your Information
What can you do with this information? First, remember that your genotype is only one piece of the puzzle. If you are concerned about how a medication—such as those for tuberculosis or high blood pressure—might affect you, do not adjust your dose or stop taking it on your own. Instead, bring your genetic report to your clinician or pharmacist. They are trained to interpret these results in the context of your complete medical history, current symptoms, and other medications. While research into NAT2 is growing, it is a tool for personalized medicine, not a self-diagnostic kit. Focus on factors you can control, such as avoiding smoking and discussing any side effects with your healthcare team.
How common is this variant?
The rs3745275 variant has a minor allele frequency of approximately 0.05 across globally diverse populations, though exact frequencies can vary significantly depending on ancestry.
Frequently asked questions
Is being a slow acetylator a medical condition?
No, being a slow acetylator is a common, normal genetic variation rather than a disease. It simply means your liver processes certain substances at a different speed than others, which is only clinically relevant if you are taking specific medications or are exposed to certain environmental toxins.
Can I use this SNP to predict my risk of cancer?
Research has shown population-level associations between slow acetylator status and a slightly higher risk of certain cancers, such as bladder cancer, especially among smokers. However, this is not a diagnostic test for cancer, and your risk is heavily influenced by lifestyle factors like tobacco use and environmental exposure.
Should I change my medication dose based on this result?
Never change your medication dosage based on a genetic report without consulting your doctor or pharmacist. They must consider your entire clinical picture, including your liver function and other medications, to determine if a dosage adjustment is safe and necessary.
Why do some populations have more slow acetylators than others?
Genetic variation in NAT2 reflects human evolutionary history and adaptation. Some scientists believe that different acetylation rates may have provided survival advantages in response to different diets or environmental conditions thousands of years ago, leading to the diverse frequencies we see today.
Sources & further reading
Educational information only, last refreshed 9/17/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Coding variant c.857G>A (p.Gly286Glu) defining the NAT2*14 allele (often associated with slow acetylation).
Coding variant c.481C>T (p.Leu161Leu) serving as a diagnostic marker for several NAT2 slow acetylator haplotypes, including *5.
Missense variant (590G>A) defining the NAT2*6A allele, associated with slow acetylator phenotype.
Synonymous polymorphism (857G>A) representing the defining mutation of the slow acetylator NAT2*7 allele.
Synonymous variant (282C>T) associated with the NAT2*6 allele, contributing to slow acetylator status.
This variant (c.590G>A, p.Arg197Gln) is a well-characterized slow acetylator allele in the NAT2 gene, influencing the metabolism of drugs like isoniazid.