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The impact of dysfunctional variants of ABCG2 on hyperuricemia and gout in pediatric-onset patients
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The impact of dysfunctional variants of ABCG2 on hyperuricemia and gout in pediatric-onset patients
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The impact of dysfunctional variants of ABCG2 on hyperuricemia and gout in pediatric-onset patients
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Journal Article
The impact of dysfunctional variants of ABCG2 on hyperuricemia and gout in pediatric-onset patients
2019
Overview
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
< 0.0001), and to the European population MAF 9.4% (OR = 5.7,
P
< 0.0001). The MAF was greatly elevated not only among pediatric-onset gout patients (42.9%) but also among patients with hyperuricemia (35.3%). Most (74%) of the pediatric-onset patients had affected family members (61% were first-degree relatives).
Conclusion
Our results show that genetic factors affecting ABCG2 function should be routinely considered in a hyperuricemia/gout diagnosis, especially in pediatric-onset patients. Genotyping of
ABCG2
is essential for risk estimation of gout/hyperuricemia in patients with very early-onset and/or a family history.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Adult
/ Age
/ Allopurinol - therapeutic use
/ ATP Binding Cassette Transporter, Subfamily G, Member 2 - genetics
/ Child
/ Febuxostat - therapeutic use
/ Female
/ Genes
/ Genetic Predisposition to Disease - genetics
/ Genomes
/ Genotype
/ Gout
/ Gout Suppressants - therapeutic use
/ Humans
/ Hyperuricemia - drug therapy
/ Male
/ Medicine
/ Patients
