UGT1A1 rs72547531: What Your Genotype Means
The rs72547531 variant is a missense single nucleotide polymorphism in the UGT1A1 gene that defines the pharmacogenomic star allele known as UGT1A1*27. This genetic variation results in altered enzyme function, leading to decreased glucuronidation capacity in hepatic metabolism. Research associates this reduced metabolic clearance with an increased susceptibility to severe drug-induced adverse reactions, particularly when treated with the chemotherapeutic agent irinotecan.
What each genotype means
| Genotype | What the research suggests | Reading |
|---|---|---|
| CC | You carry two copies of the standard reference allele. This genotype is associated with normal baseline UGT1A1 glucuronidation activity at this specific site and does not confer an elevated risk for irinotecan toxicity from this locus. | Favorable |
| CA | You carry one copy of the reference allele and one copy of the *27 missense variant. This heterozygous state is associated with moderately reduced glucuronidation capacity and may moderately elevate the risk of adverse drug reactions during irinotecan therapy. | Higher attention |
| AA | You carry two copies of the *27 missense variant. This rare homozygous genotype is linked to significantly reduced UGT1A1 catalytic activity, which can lead to impaired drug clearance and an increased risk of severe chemotherapeutic toxicity. | Higher attention |
Genomic Location and the Nature of rs72547531
The single nucleotide polymorphism designated as rs72547531 is located within a coding exon of the UGT1A1 gene on human chromosome 2. It represents a single base-pair substitution (c.686C>A) that leads to an amino acid change from proline to threonine at position 229 of the polypeptide chain (p.Pro229Thr). In standardized pharmacogenomic star nomenclature, this specific missense alteration characterizes the functional allele known as UGT1A1*27. Unlike major structural variants or non-coding promoter repeats, this change directly modifies the primary amino acid sequence of the resulting enzyme. Research cataloged in pharmacogenomic resources indicates that the altered protein folding or catalytic binding site dynamics impair the enzyme's intrinsic metabolic capacity compared to the reference wild-type allele (UGT1A1*1). Because it alters protein structure, rs72547531 has been investigated alongside other functional coding variants across global populations.
Biological Function of the UGT1A1 Enzyme
The UGT1A1 gene encodes UDP-glucuronosyltransferase family 1 member A1, a key Phase II drug-metabolizing enzyme localized predominantly in the endoplasmic reticulum of liver cells. The primary physiological role of UGT1A1 is glucuronidation, a biochemical reaction where a glucuronic acid moiety is transferred to lipophilic endogenous molecules and exogenous xenobiotics. This transformation renders hydrophobic compounds water-soluble, allowing safe clearance through bile and urine. Endogenously, UGT1A1 is the sole enzyme responsible for the metabolic clearance and detoxification of bilirubin, a breakdown product of red blood cell hemoglobin. Exogenously, UGT1A1 plays an essential role in inactivating diverse medications and their active metabolites. When variants impair UGT1A1 enzyme kinetics, substrates can accumulate to higher circulating concentrations, heightening the risk for physiological hyperbilirubinemia or heightened pharmacological drug toxicity.
Clinical Evidence: Irinotecan Toxicity and Strength of Association
Much of the clinical research surrounding UGT1A1 focuses on oncology, specifically regimens utilizing irinotecan for colorectal and other solid malignancies. In the body, irinotecan is converted into SN-38, a potent topoisomerase I inhibitor that must be glucuronidated by UGT1A1 into an inactive form (SN-38G) to prevent systemic damage. While widespread guidelines from groups like CPIC emphasize common alleles such as UGT1A1*28 and UGT1A1*6, smaller cohorts demonstrate that the UGT1A1*27 allele (rs72547531) similarly reduces glucuronidation efficiency. This decreased clearance can lead to elevated SN-38 exposure, increasing the theoretical and observed risk of dose-limiting toxicities such as life-threatening neutropenia and severe diarrhea. However, the evidence strength for rs72547531 is categorized as limited because it is based on smaller cohort studies and in vitro enzymatic assays rather than large randomized controlled clinical trials.
Population Frequency and Ancestry Patterns
The distribution of UGT1A1 variants differs markedly across ancestral backgrounds. While variants like UGT1A1*28 predominate in populations of European and African descent, coding variants such as UGT1A1*6 and UGT1A1*27 are largely characteristic of East Asian lineages. According to population databases and pharmacogenomic catalogs, the minor allele (A) for rs72547531 exists at an estimated frequency of approximately 0.01 to 0.03 (1% to 3%) in East Asian populations, including Chinese, Japanese, and Korean cohorts. Conversely, the variant allele is virtually absent or exceptionally rare among European, African, and Indigenous American populations. Because of this limited distribution, clinical screening panels developed primarily in Western cohorts rarely interrogate rs72547531, though regional guidelines in Asia increasingly acknowledge its contribution to composite metabolic deficiency.
Interpreting Results and Clinical Considerations
Identifying an rs72547531 genotype provides statistical insight into personal enzymatic capacity but does not provide a definitive diagnosis or predict absolute toxicity. Genetic results from direct-to-consumer platforms or general screening tests should never be used to initiate, discontinue, or alter any medication independently. Irinotecan toxicity is multifaceted, influenced not only by UGT1A1 alleles but also by renal function, liver health, body surface area, concomitant medications, and drug transporters like ABC and SLC families. If your genetic testing indicates the presence of a UGT1A1*27 allele and you are scheduled to receive irinotecan-based chemotherapy, discuss your results directly with your oncologist or a board-certified clinical pharmacogenomics specialist. Clinical teams evaluate overall risk profiles and can order accredited diagnostic re-testing before tailoring treatment strategies.
How common is this variant?
The minor A allele occurs at an estimated frequency of approximately 0.01 to 0.03 in East Asian populations, while remaining exceedingly rare or undetected in African and European ancestries.
Frequently asked questions
What does a higher-attention result for rs72547531 mean?
A higher-attention result indicates the presence of one or two copies of the *27 allele, which reduces UGT1A1 enzyme activity. This suggests a potential susceptibility to slower metabolism of certain medications, notably irinotecan, but it is not a diagnosis of illness.
Does having the rs72547531 variant cause Gilbert syndrome?
Gilbert syndrome is most commonly caused by homozygous promoter variants such as UGT1A1*28 in Western populations or UGT1A1*6 in Asian populations. While rs72547531 reduces enzyme activity, evidence linking it independently to Gilbert syndrome is limited, though it may contribute to reduced bilirubin clearance when inherited alongside other variants.
Should I change my cancer medication if I carry rs72547531?
No, you should never adjust, delay, or stop prescribed treatments based on genetic test results alone. Any potential modification to chemotherapeutic dosing or monitoring must be evaluated and managed by your oncologist or clinical pharmacist.
Why isn't rs72547531 included on all standard genetic panels?
Because rs72547531 is found primarily in East Asian populations and remains rare in other ancestries, standard panels developed in Western regions often prioritize more widespread alleles such as UGT1A1*28. Furthermore, the overall evidence strength for rs72547531 remains categorized as limited compared to major guideline variants.
Sources & further reading
Educational information only, last refreshed 9/5/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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