ACR: Genetic basis for poor response to allopurinol

Tuesday, 17 Nov 2015

A genetic polymorphism may explain why some people with gout fail to respond adequately to allopurinol, New Zealand researchers report.

Presenting the findings at last week’s ACR annual conference Lisa Stamp and colleagues from the University of Otago, Christchurch, New Zealand said there were a group of patients who failed to lower their serum urate levels despite adhering to 300mg of allopurinol a day.

The reasons for this were unknown but a previous genome wide association study had suggested the allele ABCG2 rs2231142 could be a determinant of poor response.

 The researchers therefore set out to investigate whether the SNP’s association with allopurinol in 264 phenotyped gout patients.

Overall 120 were considered good responders, with SU of 6 mg/dL or less on daily allopurinol of 300 mg or less, and 68 were poor responders, with SU of 6 mg/dL or higher despite a daily dose of allopurinol exceeding 300 mg.

Genotyping revealed that the minor allele of ABCG2 rs2231142 was significantly associated with poor response to allopurinol after adjusting for age, gender, BMI and ethnicity (odds ratio, 2.91; 95% confidence interval, 1.71-5.17; P = .00015).

ABCG2 genotyping may allow identification of people with gout for whom standard doses of allopurinol are unlikely to lead to therapeutic target serum urate levels, the researchers concluded. 

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