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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023728%3A_____%2F19%3AN0000077" target="_blank" >RIV/00023728:_____/19:N0000077 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/19:10397106 RIV/00064165:_____/19:10397106

Result on the web

<a href="https://doi.org/10.1186/s13075-019-1860-8" target="_blank" >https://doi.org/10.1186/s13075-019-1860-8</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s13075-019-1860-8" target="_blank" >10.1186/s13075-019-1860-8</a>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30226 - Rheumatology

Project

<a href="/en/project/NV15-26693A" target="_blank" >NV15-26693A: Function study of allelic variants of urate transporters in primary hyperuricemia and gout</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

ARTHRITIS RESEARCH & THERAPY

ISSN

1478-6354

e-ISSN

1478-6362

Volume of the periodical

21

Issue of the periodical within the volume

Art. Nr. 77

Country of publishing house

GB - UNITED KINGDOM

Number of pages

10

Pages from-to

1-10

UT code for WoS article

000462307900001

EID of the result in the Scopus database

2-s2.0-85063195778