UGT1A1 rs41475655: What Your Genotype Means
The rs41475655 variant is a genetic change located in the promoter region of the UGT1A1 gene. It is recognized as a marker for the UGT1A1*60 allele and is associated with altered enzyme activity, which may influence how the body processes certain medications like irinotecan.
What each genotype means
Normal enzyme activity
This genotype represents the most common form of the UGT1A1 promoter region, often referred to as the wild-type. Individuals with this profile typically have normal glucuronidation capacity for bilirubin and medications like irinotecan. Please discuss your medication options and any 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 (associated with the UGT1A1*60 haplotype) may result in slightly reduced UGT1A1 enzyme activity compared to those without the variant. While this is often associated with altered glucuronidation, the clinical impact can be variable and may depend on other genetic factors. Please consult your healthcare provider or pharmacist regarding how this might influence your response to specific medications.
This heterozygous genotype is common, with the T allele appearing at a frequency of approximately 0.30 in Europeans and 0.45 in African populations.
Likely reduced enzyme activity
Having two copies of the T allele is associated with the UGT1A1*60 variant, which can lead to decreased UGT1A1 enzyme function and potentially higher levels of certain medications or bilirubin in the blood. Research suggests this may increase the risk of side effects for drugs metabolized by this enzyme, such as irinotecan. It is important to discuss this result with your clinician or pharmacist before starting any new medication therapy.
This homozygous genotype is less common than the heterozygous form but is present in a significant portion of the population, particularly in those of African ancestry.
Understanding the SNP and Its Location
The variant rs41475655 is a single nucleotide polymorphism (SNP) situated within the promoter region of the UGT1A1 gene. This specific location is critical because the promoter region acts as a control center, determining how much of the UGT1A1 enzyme is produced by the body. This variant is often used to define the UGT1A1*60 allele, a genetic signature that researchers track to understand variations in enzyme expression. Because it sits in a regulatory area, changes here can lead to differences in the efficiency of the UGT1A1 enzyme, which is responsible for breaking down various substances, including bilirubin and certain chemotherapy drugs. By studying this SNP, scientists aim to better predict how genetic differences might lead to variations in drug metabolism between individuals.
The Role of the UGT1A1 Gene
The UGT1A1 gene provides instructions for making an enzyme called UDP-glucuronosyltransferase 1A1. This enzyme plays a vital role in the liver by performing a process called glucuronidation, which makes substances more water-soluble so they can be easily excreted from the body. One of its primary natural tasks is to process bilirubin, a byproduct of the normal breakdown of red blood cells. When the UGT1A1 enzyme is less active, bilirubin can build up in the blood, potentially leading to jaundice. Beyond its natural functions, this enzyme is also responsible for detoxifying and clearing specific medications, most notably the chemotherapy drug irinotecan. If the enzyme is not functioning at full capacity, the body may struggle to clear these drugs, which can lead to higher concentrations of the medication in the system and an increased risk of side effects.
Research Associations and Evidence Strength
Research into rs41475655 and the broader UGT1A1 gene has primarily focused on pharmacogenomics, specifically how these variants influence the safety of irinotecan therapy. Studies have shown that individuals with certain UGT1A1 variants may experience a higher risk of severe neutropenia—a dangerous drop in white blood cell counts—and hyperbilirubinemia when treated with irinotecan. While the evidence linking UGT1A1 variants to toxicity is strong, the specific contribution of rs41475655 is often studied in conjunction with other variants like UGT1A1*28 and UGT1A1*6. Because of this, the evidence strength for this specific SNP is considered limited compared to more established markers. Clinical guidelines often emphasize the importance of testing for multiple UGT1A1 variants to get a complete picture of a patient's metabolic profile before starting treatment.
Population Frequency
The frequency of the rs41475655 variant varies significantly across different global populations. Current data indicates a minor allele frequency of approximately 0.30 in European populations and roughly 0.45 in African populations. These differences highlight the importance of considering ancestry when interpreting genetic data, as the prevalence of specific genotypes can change the likelihood of observing certain drug responses within a community. Because this variant is relatively common, many individuals carry at least one copy of the allele, though this does not automatically mean they will experience adverse reactions to medication. Understanding these population-level frequencies helps researchers design more inclusive studies and helps clinicians recognize that genetic risk factors are not distributed equally across all groups.
What You Can and Cannot Do With This Information
It is important to understand that genetic information is only one piece of a much larger health puzzle. You cannot use this information to diagnose yourself with a condition or to predict with certainty how you will react to a specific medication. Many factors, including age, liver function, other medications, and overall health, influence how your body processes drugs. If you have concerns about your genetic profile or are scheduled to begin a treatment like irinotecan, the most important step is to discuss this with your oncologist or pharmacist. They can interpret your genetic results in the context of your full medical history and determine if a dose adjustment is necessary. Never make changes to your prescribed medication regimen based on genetic test results without direct guidance from your healthcare provider.
How common is this variant?
The minor allele frequency for rs41475655 is approximately 0.30 in Europeans and 0.45 in African populations.
Frequently asked questions
What is the UGT1A1 gene?
The UGT1A1 gene provides instructions for an enzyme that helps the liver process and remove substances like bilirubin and certain drugs from the body.
Does this variant mean I will have side effects from chemotherapy?
Not necessarily. While this variant is associated with an increased risk of side effects like neutropenia, many other factors influence how you respond to medication. Always consult your doctor to discuss your specific risks.
Should I get tested for UGT1A1 variants?
Genetic testing for UGT1A1 is often recommended for patients before starting specific chemotherapy regimens like irinotecan. Talk to your oncologist to see if this testing is appropriate for your treatment plan.
Can I change my UGT1A1 genotype?
No, your genotype is inherited from your parents and cannot be changed. However, knowing your genotype can help your healthcare team personalize your medical care.
Sources & further reading
Educational information only, last refreshed 9/22/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Missense variant corresponding to the functional UGT1A1*27 allele associated with reduced glucuronidation and elevated irinotecan toxicity risk.
Missense alteration associated with reduced glucuronidation capacity and increased susceptibility to irinotecan toxicity and hyperbilirubinemia.
This variant in the UGT1A gene cluster is associated with serum total bilirubin levels and susceptibility to Gilbert syndrome.
This variant (UGT1A1*6) is a decreased-function allele associated with reduced glucuronidation capacity, impacting the metabolism of drugs like irinotecan and influencing neonatal hyperbilirubinemia risk.
This variant is a key marker for defining UGT1A1 star alleles (*1, *28, *36, *37) which influence the metabolism of drugs like irinotecan and the risk of hyperbilirubinemia.
This variant is associated with hyperbilirubinaemia (Gilbert's syndrome) and is used to guide irinotecan dosage.