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The impact of dysfunctional variants of ABCG2 on hyperuricemia and gout in pediatric-onset patients.

ABSTRACT: BACKGROUND:ABCG2 is a high-capacity urate transporter that plays a crucial role in renal urate overload and extra-renal urate underexcretion. Previous studies have suggested an association between hyperuricemia and gout susceptibility relative to dysfunctional ABCG2 variants, with rs2231142 (Q141K) being the most common. In this study, we analyzed the ABCG2 gene in a hyperuricemia and gout cohort focusing on patients with pediatric-onset, i.e., before 18?years of age. METHOD:The cohort was recruited from the Czech Republic (n =?234) and consisted of 58 primary hyperuricemia and 176 gout patients, with a focus on pediatric-onset patients (n =?31, 17 hyperuricemia/14 gouts); 115 normouricemic controls were used for comparison. We amplified, sequenced, and analyzed 15 ABCG2 exons. The chi-square goodness-of-fit test was used to compare minor allele frequencies (MAF), and the log-rank test was used to compare empirical distribution functions. RESULTS:In the pediatric-onset cohort, two common (p.V12M, p.Q141K) and three very rare (p.K360del, p.T421A, p.T434M) allelic ABCG2 variants were detected. The MAF of p.Q141K was 38.7% compared to adult-onset MAF 21.2% (OR?=?2.4, P =?0.005), to the normouricemic controls cohort MAF 8.5% (OR?=?6.8, P

SUBMITTER: Stiburkova B

PROVIDER: S-EPMC6425717 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Identification of Two Dysfunctional Variants in the ABCG2 Urate Transporter Associated with Pediatric-Onset of Familial Hyperuricemia and Early-Onset Gout.

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