CYP2A6 rs28399433: Understanding This Genetic Variant
The genetic variant rs28399433 is a single nucleotide polymorphism located within the CYP2A6 gene. It is primarily studied for its potential influence on the metabolism of nicotine and other substrates processed by the CYP2A6 enzyme.
What each genotype means
Typical metabolic profile
This genotype represents the most common form of this genetic marker. Research into this specific variant, also known as -47A>C, has primarily focused on its potential role in drug metabolism and smoking behavior, though evidence remains limited. Please discuss any concerns regarding medication response or dosing with your clinician or pharmacist.
This is the most common genotype observed in most global populations.
Heterozygous metabolic profile
You carry one copy of the A allele and one copy of the C allele for this variant. While this marker is studied in the context of drug metabolism and behavioral traits, current evidence is not sufficient to suggest a significant clinical impact on its own. Always consult with your healthcare provider before making changes to your medication regimen.
This genotype is found in a significant portion of the population, with a global minor allele frequency of approximately 13%.
Variant metabolic profile
You carry two copies of the C allele for this variant. This marker has been investigated in studies regarding drug metabolism and smoking-related traits, but the clinical significance of this specific genotype is not well-established. Please consult your pharmacist or physician if you have questions about how your genetics might influence your response to specific medications.
This genotype is less common than the AA or AC genotypes in most studied populations.
What is rs28399433?
The variant rs28399433 is a specific change in the DNA sequence located on chromosome 19. In scientific literature, it is often referred to as a promoter polymorphism within the CYP2A6 gene. A single nucleotide polymorphism, or SNP, represents a variation at a single position in the DNA sequence among individuals. While the human genome is remarkably similar across all people, these small variations can lead to differences in how our bodies function, including how we process various substances. Researchers track these specific locations to understand how they might correlate with physiological traits or responses to external compounds. Because this variant is situated in a regulatory region of the gene, it is hypothesized to potentially affect the expression levels of the associated enzyme, though the functional impact can vary depending on the specific biological context and the presence of other genetic factors.
The Role of the CYP2A6 Gene
The CYP2A6 gene provides instructions for making an enzyme that belongs to the cytochrome P450 family. These enzymes are primarily responsible for the metabolism of a wide range of substances, including drugs, toxins, and endogenous compounds. CYP2A6 is particularly well-known for its role in the metabolism of nicotine, the primary addictive component in tobacco products. By breaking down nicotine into cotinine, the enzyme helps the body clear the substance from the system. Variations in the CYP2A6 gene can lead to differences in enzyme activity, which may influence how quickly an individual metabolizes nicotine. This, in turn, has been a subject of extensive research regarding smoking behavior and tobacco dependence. Understanding the function of this gene is essential for researchers investigating why individuals may have different physiological responses to nicotine exposure or certain medications that are also processed by this specific enzyme pathway.
Research Associations and Evidence
Research into rs28399433 has primarily focused on its association with CYP2A6 enzyme activity. Some studies have suggested that individuals carrying certain alleles at this position may exhibit reduced enzyme metabolism, which could theoretically impact the rate at which nicotine is cleared from the body. However, the evidence regarding the clinical impact of this specific SNP is considered moderate. While some studies have explored its potential link to smoking behaviors or susceptibility to certain conditions, results can be mixed or dependent on the specific population studied. It is important to note that genetic associations are complex and rarely determined by a single variant alone. Many factors, including environmental influences and other genetic markers, contribute to an individual's metabolic profile. Consequently, while rs28399433 is a useful marker in research settings, it is not currently used as a standalone diagnostic tool for predicting individual health outcomes or drug responses.
What You Can Do With This Information
Information about genetic variants like rs28399433 is primarily intended for educational and research purposes. If you have received genetic testing results that include this variant, it is important to understand that this information does not constitute a medical diagnosis. Genetic data is complex, and the presence of a specific genotype does not guarantee a particular health outcome or metabolic rate. You should never use this information to make decisions about your health, such as starting or stopping medications, without consulting a qualified healthcare professional. If you are concerned about how your body processes a specific medication or if you are interested in how your genetics might influence your health, discuss these topics with your doctor or a pharmacist. They can provide context based on your full medical history and current clinical guidelines, ensuring that any decisions regarding your care are based on comprehensive, evidence-based information.
How common is this variant?
The frequency of the rs28399433 variant varies across different ancestral populations. Global minor allele frequency data indicates that this SNP is present at a moderate frequency, though specific percentages can differ significantly between ethnic groups.
Frequently asked questions
What does rs28399433 mean for my health?
The rs28399433 variant is a research marker and does not provide a medical diagnosis. It is studied for its potential role in enzyme metabolism, but it is not used to predict individual health outcomes or disease risk.
Does this variant affect how I process medications?
While the CYP2A6 enzyme is involved in the metabolism of certain substances, the clinical impact of rs28399433 on specific medications is not fully established. Always consult your doctor or pharmacist before making any changes to your medication regimen.
Is rs28399433 the same as a CYP2B6 variant?
No, rs28399433 is located in the CYP2A6 gene. While both CYP2A6 and CYP2B6 are members of the cytochrome P450 family, they are distinct genes with different functions and locations in the genome.
Where can I find more information about this SNP?
You can find technical information about this variant in public databases like dbSNP or the GWAS Catalog. These resources provide data on the location, frequency, and published research associated with the variant.
Sources & further reading
Educational information only, last refreshed 10/5/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Defines the non-functional CYP2B6*18 allele (c.983T>C; p.Ile328Thr) leading to impaired metabolism of efavirenz.
Core coding variant c.1459C>T (p.Arg487Cys) defining CYP2B6*5, associated with reduced clearance of substrates.
Key variant defining the CYP2B6*6 reduced-function allele influencing efavirenz, methadone, and bupropion clearance.
Missense alteration defining the CYP2B6*18 allele, causing profound enzymatic deficiency and impaired clearance of efavirenz and methadone.
A coding variant that defines the decreased-function CYP2B6*4 allele, influencing plasma concentrations of efavirenz, methadone, and bupropion.
Missense alteration defining the nonfunctional CYP2B6*18 allele common in African populations that slows clearance of efavirenz.