NAT2 rs1800559: Understanding Your Acetylation Status
The rs1800559 variant is a specific genetic change within the NAT2 gene that influences how your body processes certain medications. It is primarily associated with the 'slow-acetylator' phenotype, which can affect the risk of side effects when taking drugs like isoniazid for tuberculosis.
What each genotype means
Normal enzyme activity
This genotype represents the presence of the reference allele at this position, which is typically associated with normal NAT2 enzyme function. Individuals with this genotype are more likely to be rapid or intermediate acetylators, meaning they process medications like isoniazid more efficiently. Please discuss your medication dosing and potential side effects with your clinician or pharmacist.
This is the most common genotype in many populations, though frequencies vary significantly by ancestry.
Reduced enzyme activity
Carrying one copy of the T allele at this position is associated with a decrease in NAT2 enzyme activity compared to those with two C alleles. This genotype is often found in individuals classified as intermediate or slow acetylators, which may influence how your body metabolizes drugs like isoniazid. Please discuss your medication dosing and potential side effects with your clinician or pharmacist.
This genotype is common, appearing in a significant portion of the population across European and East Asian ancestries.
Low enzyme activity
This genotype indicates you carry two copies of the T allele, which is a defining component of several 'slow acetylator' NAT2 alleles, such as NAT2*6. Individuals with this genotype may process certain medications, including isoniazid, more slowly, which can increase the risk of drug-induced side effects like hepatotoxicity. Please discuss your medication dosing and potential side effects with your clinician or pharmacist.
This genotype is found in a substantial percentage of the population, with prevalence varying by geographic and ethnic background.
What is the rs1800559 Variant?
The rs1800559 variant is a single nucleotide polymorphism (SNP) located within the NAT2 gene, which provides instructions for making the N-acetyltransferase 2 enzyme. In the context of this variant, a cytosine (C) is replaced by a thymine (T) at a specific position in the DNA sequence. This change is a defining feature of the NAT2*6 allele family. Because this variant is located in a region of the gene that influences enzyme function, it is categorized as a pharmacogenomic marker. Pharmacogenomics is the study of how your unique genetic makeup influences your body's response to drugs. By identifying whether you carry this variant, researchers can better understand why individuals metabolize medications at different speeds, which is a critical factor in determining both the effectiveness and the safety of various therapeutic treatments.
The Role of the NAT2 Gene
The NAT2 gene encodes an enzyme responsible for the phase II metabolism of many drugs and environmental toxins. This process, known as acetylation, involves adding an acetyl group to a substance to make it easier for the body to eliminate. The efficiency of this enzyme varies significantly between people, leading to three distinct categories: rapid, intermediate, and slow acetylators. Individuals with two high-activity alleles are typically rapid acetylators, while those with two low-activity variants—such as those carrying the rs1800559 T allele—are classified as slow acetylators. Because slow acetylators process certain medications more slowly, these drugs can remain in the bloodstream for longer periods. This prolonged exposure can sometimes lead to higher drug concentrations, which may increase the likelihood of experiencing adverse reactions or toxicity if the dosage is not adjusted appropriately for the individual's metabolic rate.
Research and Clinical Associations
Research has consistently linked the slow-acetylator phenotype to an increased risk of anti-tuberculosis drug-induced hepatotoxicity, particularly when patients are treated with isoniazid. Because slow acetylators cannot clear the drug as quickly as rapid acetylators, the drug may accumulate, potentially stressing the liver. Meta-analyses have shown that individuals with the slow-acetylator phenotype have a significantly higher risk of liver-related side effects compared to those with rapid or intermediate phenotypes. However, it is important to note that while the association is statistically significant, the evidence strength is considered limited in terms of universal clinical application. Factors such as age, diet, and other medications can also influence liver health. Consequently, while genetic testing for NAT2 variants is a subject of ongoing research for precision medicine, it is not currently a standard requirement for every patient. Always consult with your healthcare provider or pharmacist to discuss how your genetic profile might relate to your specific treatment plan.
Population Frequency
The frequency of the rs1800559 variant varies significantly across different global populations. In European populations, the minor allele frequency is typically observed between 25% and 35%, while in East Asian populations, it is generally found at a lower frequency of approximately 10% to 20%. These differences reflect the diverse evolutionary history of human populations and the varying prevalence of slow-acetylator phenotypes worldwide.
What You Can Do With This Information
Understanding your genetic status regarding NAT2 can be a valuable piece of information to share with your medical team, especially if you are prescribed medications metabolized by this enzyme, such as isoniazid. If you have access to genetic testing results, you should bring them to your doctor or a clinical pharmacist. They are the only professionals qualified to interpret these results in the context of your overall health, current medications, and medical history. You cannot use this information to diagnose yourself or to make independent decisions about your medication dosages. Never stop or change the dose of a prescribed medication based on genetic data without explicit guidance from your clinician. Genetic information is just one factor in a complex biological system, and your healthcare provider will use it alongside other clinical markers to ensure your treatment is as safe and effective as possible.
How common is this variant?
The minor allele frequency for rs1800559 is approximately 25-35% in Europeans and 10-20% in East Asians.
Frequently asked questions
Does having the TT genotype mean I will definitely have liver problems?
No, having the TT genotype does not guarantee you will experience liver issues. It simply means you are a slow acetylator, which is a risk factor that your doctor should be aware of when prescribing certain medications.
Should I get tested for NAT2 variants before starting medication?
Routine genetic testing for NAT2 is not currently standard practice for everyone. You should discuss the necessity of such testing with your healthcare provider based on the specific medication you are being prescribed.
Can I change my acetylator status through diet or lifestyle?
Your acetylator status is determined by your genetics and cannot be changed. However, maintaining a healthy lifestyle and monitoring your liver health with your doctor can help manage risks associated with medication metabolism.
Is rs1800559 the only variant that affects NAT2?
No, the NAT2 gene has many different variants that contribute to the overall acetylation phenotype. The rs1800559 SNP is just one of several markers used to determine if someone is a slow, intermediate, or rapid acetylator.
Sources & further reading
Educational information only, last refreshed 9/29/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Coding variant c.481C>T (p.Leu161Leu) serving as a diagnostic marker for several NAT2 slow acetylator haplotypes, including *5.
Coding variant c.857G>A (p.Gly286Glu) defining the NAT2*14 allele (often associated with slow acetylation).
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.
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.
Tag SNP defining the rapid versus slow N-acetyltransferase 2 acetylator phenotype, showing substantial allele frequency divergence across world ancestries.