Allopurinol

Xanthine oxidase turns hypoxanthine into xanthine and xanthine into uric acid. Allopurinol, which resembles hypoxanthine, blocks the enzyme, and the body converts it to oxypurinol, which also blocks it and is thought to carry most of the drug's effect. About 90% of a dose is absorbed. Allopurinol itself has a half-life of 1 to 2 hours, but oxypurinol has a half-life of about 15 hours, and the kidneys eliminate both [3].

For gout, the label starts at 100 mg a day and raises the dose by 100 mg each week until uric acid is 6 mg/dL or lower, up to 800 mg a day; people with reduced kidney function start at 50 mg. Mild gout is usually controlled with 200 to 300 mg a day and moderate to severe tophaceous gout with 400 to 600 mg. Gout flares can happen when treatment starts, so the label recommends preventive treatment with colchicine or an anti-inflammatory drug during that period [3].

ABCG2 makes an efflux transporter (also called BCRP) that moves uric acid out of the body through the kidneys and intestine. Its p.Gln141Lys variant (Q141K, rs2231142, also written c.421C>A) reduces the transporter's activity and is linked to high uric acid and gout. Oxypurinol is also carried by the transporter, so in theory the variant could work in either direction: less oxypurinol excretion would strengthen the drug, while less uric acid excretion means more inhibition is needed. The clinical studies point to a weaker response [2].

The variant is common, and much more so in some populations:

These are the Clinical Pharmacogenetics Implementation Consortium's (CPIC) estimates, pooled from published studies [4].

A genome-wide study of 2,027 people taking allopurinol in the Kaiser Permanente GERA cohort found ABCG2 associated with how much uric acid fell, with rs2231142 linked to a smaller response; laboratory work showed that the transporter carries allopurinol [1]. In a study of 264 people with gout, in which adherence was checked by measuring oxypurinol, the variant was associated with 2.71 times the odds of a poor response, defined as uric acid of 6 mg/dL or more despite more than 300 mg a day, after adjusting for kidney function, diuretic use and other factors [5]. The DPWG reviewed nine articles: five of the eight studies, and one case report, showed reduced effectiveness. In one, a poor response was 2.0 times as common in people with one copy and 2.8 times as common in people with two [2].

ABCG2 and dosing

The DPWG published its ABCG2 and allopurinol guideline in 2022, and its authors found no other guideline on this gene and drug [2]; the US Food and Drug Administration (FDA) lists allopurinol only with HLA-B*58:01 [6]. The DPWG recommends a higher dose for people with the variant. The dose factors come from a single study of people with gout whose dose was raised until uric acid fell below 0.36 mmol/L (about 6 mg/dL). DPWG rates testing ABCG2 before starting allopurinol as "potentially beneficial", meaning it can be considered case by case [2] [7].

A Gene2Rx report shows DPWG's interpretation of your ABCG2 result, including whether a higher dose is likely to be needed to reach the uric acid target.

HLA-B*58:01 and severe skin reactions

Allopurinol can cause rare but serious reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis and DRESS (drug reaction with eosinophilia and systemic symptoms), in about 5 of every 10,000 people who take it. People who carry the HLA-B*58:01 allele are at higher risk, although reactions also occur in people who do not carry it. The label says allopurinol is not recommended for carriers unless the benefits clearly outweigh the risks, and it suggests considering screening before treatment in populations where the allele is common. The allele is found in about 8 to 10% of Han Chinese people, about 8% of Thai, about 6% of Korean, about 4% of Black, 1 to 2% of Indigenous American and Hispanic, and under 1% of European and Japanese people [3].

CPIC's guideline states that allopurinol is contraindicated in HLA-B*58:01 carriers, a strong recommendation [8], and a 2015 review left that advice unchanged [9]. The FDA's Table of Pharmacogenetic Associations lists the allele as raising the risk of severe skin reactions [6]. The DPWG recommends an alternative such as febuxostat for carriers; it estimates that 1.6 to 2.0% of carriers who take allopurinol develop a severe skin reaction, rising to 8 to 18% in people with chronic kidney disease, and that about 11% of these reactions are fatal [2]. Gene2Rx does not call HLA genes, so your report cannot tell you whether you carry HLA-B*58:01.

Allopurinol is already adjusted step by step until uric acid reaches its target, so an ABCG2 result mainly helps explain why a person may need a higher dose than usual, or why uric acid stays high on a standard dose. Bring the report to your prescriber with your recent uric acid and kidney function results, your current dose and a list of your medicines. Do not start, stop or change allopurinol on the basis of a genetic result; make any change together with your prescriber.

Medicines that interact with allopurinol

Allopurinol changes the levels of some other drugs. It blocks the breakdown of mercaptopurine and azathioprine, so the label calls for reducing their doses, and it advises avoiding it with capecitabine, whose active metabolites it can lower. In the other direction, uricosuric drugs speed up the excretion of oxypurinol and can weaken allopurinol's effect. Thiazide diuretics, ampicillin, amoxicillin and bendamustine may raise the risk of skin rash [3].

Other factors that matter

Kidney function affects dosing, because the kidneys clear oxypurinol; the label recommends lower doses when kidney function is reduced. Taking the medicine every day also matters: the study above measured oxypurinol to set aside people who were not taking their tablets before looking at genetics [5]. The label advises stopping allopurinol and seeking medical attention promptly at the first sign of a skin rash [3].

An ABCG2 result describes one inherited influence on how well allopurinol lowers uric acid. It does not measure your uric acid, and it cannot show why a particular dose is or is not working; dose, adherence and kidney function also affect the response. It says nothing about the risk of a severe skin reaction, which depends on HLA-B*58:01 and is not assessed.

Consumer arrays (23andMe, AncestryDNA, MyHeritage) are not clinical-grade tests, and their raw data is labeled not for medical use. They read fixed positions in the genome. Array processing uses imputation to infer some variants that were not measured directly, but a variant at a position your data does not cover cannot be seen; a normal result means that the assessed variant was not found among the positions your data covers.

If you might take allopurinol and come from a population in which HLA-B*58:01 is common, or have kidney disease, ask your prescriber about a clinical HLA-B*58:01 test before starting. That decision is about safety and cannot be made from a Gene2Rx report.

Does Gene2Rx tell me whether I am at risk of the severe allopurinol rash?

No. That risk is linked to HLA-B*58:01, which Gene2Rx does not test (see HLA-B*58:01 and severe skin reactions). A clinical laboratory can test for it.

My uric acid is still high on allopurinol. Is it my ABCG2 result?

It may contribute, since the variant is linked to a weaker response, but dose, adherence and kidney function also matter (see Using your result). The usual approach is to keep adjusting the dose toward the target with your prescriber.

Is this the same ABCG2 result used for rosuvastatin?

Yes. The same variant, rs2231142, also matters for the cholesterol medicine rosuvastatin; that page explains how.

1. Wen CC et al. Genome-wide association study identifies ABCG2 (BCRP) as an allopurinol transporter and a determinant of drug response. Clin Pharmacol Ther (2015). The genome-wide study of allopurinol response.
2. van der Pol KH et al. Dutch Pharmacogenetics Working Group guideline for the gene-drug interaction of ABCG2, HLA-B and allopurinol, and MTHFR, folic acid and methotrexate. Eur J Hum Genet (2022). DPWG's evidence review and recommendations for ABCG2 and HLA-B*58:01.
3. Allopurinol tablets (Dr. Reddy's): prescribing information, revised 6/2025. DailyMed. Dosing, pharmacokinetics, HLA-B*58:01 warning and drug interactions.
4. CPIC. ABCG2 frequency table (spreadsheet). Phenotype frequencies by population group.
5. Roberts RL et al. ABCG2 loss-of-function polymorphism predicts poor response to allopurinol in patients with gout. Pharmacogenomics J (2017). Poor response by genotype in patients with confirmed adherence.
6. US Food and Drug Administration. Table of Pharmacogenetic Associations. The allopurinol and HLA-B*58:01 entry (Section 2).
7. Annotation of DPWG clinical guideline for allopurinol and ABCG2. ClinPGx. The current DPWG recommendation text and testing advice.
8. Hershfield MS et al. Clinical Pharmacogenetics Implementation Consortium guidelines for human leukocyte antigen-B genotype and allopurinol dosing. Clin Pharmacol Ther (2013). CPIC's HLA-B*58:01 recommendation.
9. Saito Y et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for human leukocyte antigen B (HLA-B) genotype and allopurinol dosing: 2015 update. Clin Pharmacol Ther (2016). Confirms CPIC's 2013 HLA-B*58:01 recommendations.