Effect of ABCG2 Variants on Pediatric-Onset Hyperuricemia and Gout

Researcher examining genetic test results
Researcher viewing results of a genetic test on a digital tablet.
Researchers examined the ABCG2 gene in a hyperuricemia and gout cohort, focusing on patients with pediatric-onset disease.

Genetic factors affecting ABCG2 function need to be considered during differential diagnosis of pediatric-onset hyperuricemia and gout, according to data published in Arthritis Research & Therapy.

ABCG2 is a high-capacity urate transporter that affects renal urate overload and extrarenal urate undersecretion. The investigators of this study sought to analyze the ABCG2 gene in a hyperuricemia and gout cohort, focusing on those patients with disease onset <18 years. A total of 234 patients made up the cohort, 58 of whom had primary hyperuricemia and 176 of whom had gout. The pediatric-onset cohort included 31 patients, 17 of whom had hyperuricemia and 14 of whom had gout; 115 normouricemic control patients were used as comparators. Overall, 15 ABCG2 exons were amplified, sequenced, and analyzed.

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There were 2 common (p.V12M and p.Q141K) and 3 very rare (p.K360del, p.421A, and p.T434M) allelic ABCG2 variants detected in the pediatric-onset cohort. The minor allele frequency (MAF) of p.Q141K in the pediatric-onset cohort was 38.7% compared with a 21.2% MAF (odds ratio [OR], 2.4; P =.005) in adult-onset patients, an 8.5% MAF (OR, 6.8; P <.0001) in normouricemic control patients, and a 9.4% MAF (OR, 5.7; P <.0001) in a European population.

In addition, the MAF of p.Q141K was 35.3% (4 homozygotes, 4 heterozygotes) among the 17 patients with pediatric-onset hyperuricemia and 42.9% (3 homozygotes, 6 heterozygotes) among the 14 patients with pediatric-onset gout, which signifies that a high frequency of p.Q141K was detected not only among patients with symptomatic gout but also among those with asymptomatic hyperuricemia. Most of the pediatric-onset patients had affected family members, 61% of whom were first-degree relatives.

The investigators concluded that genotyping of ABCG2 is essential for risk estimation of gout and hyperuricemia in patients with very early disease onset or a family history. The benefits of early initiation of urate-lowering treatment in patients with pediatric-onset disease who have a strong genetic risk require careful analysis. A discussion regarding the value of a personalized approach to the management of hyperuricemia in clinical practice is necessary.


Stiburkova B, Pavelcova K, Pavlikova M, Ješina P, Pavelka K. The impact of dysfunctional variants of ABCG2 on hyperuricemia and gout in pediatric-onset patients. Arthritis Res Ther. 2019;21(1):77.