Allopurinol

Allopurinol (brand names Zyloprim and Aloprim) is the first-line urate-lowering therapy for chronic gout and tumor lysis syndrome. It is a xanthine oxidase inhibitor: by blocking the enzyme that produces uric acid, it lowers serum uric acid and prevents gout flares and tophi.

Gene2Rx covers ABCG2, the urate transporter that explains a meaningful share of variation in allopurinol response between patients.

ABCG2 encodes a urate efflux transporter (BCRP) in the kidney and gut. The Q141K variant (rs2231142) reduces transporter function. Reduced-function carriers have higher baseline uric acid and tend to respond less well to allopurinol than non-carriers; they often need higher doses or a switch to alternative urate-lowering therapy.

ABCG2 reduced-function carriers achieve smaller serum-urate reductions on standard allopurinol doses. Higher allopurinol doses are often needed to reach target urate (under 6 mg/dL); some patients require switching to febuxostat, which is a different xanthine oxidase inhibitor less affected by ABCG2.

ABCG2 Normal Function

• Effect: Standard urate-lowering response.
• Recommendation: Standard dosing; titrate to target urate (under 6 mg/dL).

ABCG2 Reduced Function

• Effect: Smaller reduction in serum uric acid at standard doses.
• Clinical consequence: May not reach target urate on routine doses.
• Recommendation: May require higher allopurinol doses; if target not reached, consider febuxostat.

Indeterminate / Not Available

• Recommendation: Standard dosing; titrate to urate target.

Allopurinol carries a separate, well-known safety concern that is not based on the ABCG2 genetics covered in your Gene2Rx report. The HLA-B*58:01 allele is strongly associated with allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS / TEN). The allele is most common in Han Chinese and other East Asian populations. Gene2Rx does not currently test HLA alleles. If your ancestry includes populations where HLA-B*58:01 is common, ask your prescriber whether HLA-B*58:01 testing is appropriate before starting allopurinol; that testing is offered separately by clinical pharmacogenetic laboratories.

For ABCG2 reduced-function patients who do not reach target urate on allopurinol, alternatives include febuxostat (Uloric), probenecid, lesinurad, and pegloticase.

• DPWG, Pharmacogenetics Working Group recommendations
• FDA, Table of Pharmacogenetic Associations

Learn more about how genetics may affect your response to Allopurinol and related medications:

• Allopurinol Not Working for Gout? ABCG2 Pharmacogenetics Explained