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The Role of ABCG2 in the Pathogenesis of Primary Hyperuricemia and Gout—An Update
Urate homeostasis in humans is a complex and highly heritable process that involves i.e., metabolic urate biosynthesis, renal urate reabsorption, as well as renal and extrarenal urate excretion. Importantly, disturbances in urate excretion are a common cause of hyperuricemia and gout. The majority o...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268734/ https://www.ncbi.nlm.nih.gov/pubmed/34206432 http://dx.doi.org/10.3390/ijms22136678 |
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author | Eckenstaler, Robert Benndorf, Ralf A. |
author_facet | Eckenstaler, Robert Benndorf, Ralf A. |
author_sort | Eckenstaler, Robert |
collection | PubMed |
description | Urate homeostasis in humans is a complex and highly heritable process that involves i.e., metabolic urate biosynthesis, renal urate reabsorption, as well as renal and extrarenal urate excretion. Importantly, disturbances in urate excretion are a common cause of hyperuricemia and gout. The majority of urate is eliminated by glomerular filtration in the kidney followed by an, as yet, not fully elucidated interplay of multiple transporters involved in the reabsorption or excretion of urate in the succeeding segments of the nephron. In this context, genome-wide association studies and subsequent functional analyses have identified the ATP-binding cassette (ABC) transporter ABCG2 as an important urate transporter and have highlighted the role of single nucleotide polymorphisms (SNPs) in the pathogenesis of reduced cellular urate efflux, hyperuricemia, and early-onset gout. Recent publications also suggest that ABCG2 is particularly involved in intestinal urate elimination and thus may represent an interesting new target for pharmacotherapeutic intervention in hyperuricemia and gout. In this review, we specifically address the involvement of ABCG2 in renal and extrarenal urate elimination. In addition, we will shed light on newly identified polymorphisms in ABCG2 associated with early-onset gout. |
format | Online Article Text |
id | pubmed-8268734 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82687342021-07-10 The Role of ABCG2 in the Pathogenesis of Primary Hyperuricemia and Gout—An Update Eckenstaler, Robert Benndorf, Ralf A. Int J Mol Sci Review Urate homeostasis in humans is a complex and highly heritable process that involves i.e., metabolic urate biosynthesis, renal urate reabsorption, as well as renal and extrarenal urate excretion. Importantly, disturbances in urate excretion are a common cause of hyperuricemia and gout. The majority of urate is eliminated by glomerular filtration in the kidney followed by an, as yet, not fully elucidated interplay of multiple transporters involved in the reabsorption or excretion of urate in the succeeding segments of the nephron. In this context, genome-wide association studies and subsequent functional analyses have identified the ATP-binding cassette (ABC) transporter ABCG2 as an important urate transporter and have highlighted the role of single nucleotide polymorphisms (SNPs) in the pathogenesis of reduced cellular urate efflux, hyperuricemia, and early-onset gout. Recent publications also suggest that ABCG2 is particularly involved in intestinal urate elimination and thus may represent an interesting new target for pharmacotherapeutic intervention in hyperuricemia and gout. In this review, we specifically address the involvement of ABCG2 in renal and extrarenal urate elimination. In addition, we will shed light on newly identified polymorphisms in ABCG2 associated with early-onset gout. MDPI 2021-06-22 /pmc/articles/PMC8268734/ /pubmed/34206432 http://dx.doi.org/10.3390/ijms22136678 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Eckenstaler, Robert Benndorf, Ralf A. The Role of ABCG2 in the Pathogenesis of Primary Hyperuricemia and Gout—An Update |
title | The Role of ABCG2 in the Pathogenesis of Primary Hyperuricemia and Gout—An Update |
title_full | The Role of ABCG2 in the Pathogenesis of Primary Hyperuricemia and Gout—An Update |
title_fullStr | The Role of ABCG2 in the Pathogenesis of Primary Hyperuricemia and Gout—An Update |
title_full_unstemmed | The Role of ABCG2 in the Pathogenesis of Primary Hyperuricemia and Gout—An Update |
title_short | The Role of ABCG2 in the Pathogenesis of Primary Hyperuricemia and Gout—An Update |
title_sort | role of abcg2 in the pathogenesis of primary hyperuricemia and gout—an update |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268734/ https://www.ncbi.nlm.nih.gov/pubmed/34206432 http://dx.doi.org/10.3390/ijms22136678 |
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