ArticleRheumatology (Oxford, England)2021
Substantial anti-gout effect conferred by common and rare dysfunctional variants of URAT1/SLC22A12.
Article in Rheumatology (Oxford, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- Gene-environment interaction modifies the association between hyperinsulinemia and serum urate levels through SLC22A12.The Journal of clinical investigation · 2025Trial
- A case of renal hypouricemia type 1 associated with compound heterozygous URAT1/SLC22A12 variants A209V and F379L: clinical evidence for their pathogenic significance.CEN case reports · 2026Article
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Preliminary analysis of lifestyle and genetic factors for hyperuricemia and gout prevalence in the Yunnan Miao population of China.Frontiers in genetics · 2026Article
- The pathogenesis of gout: molecular insights from genetic, epigenomic and transcriptomic studies.Nature reviews. Rheumatology · 2024Review
- Biochemical characterization of renal hypouricemia-associated mutations in urate transporter genes using human cells.Human cell · 2024Article
- Establishment of Polydopamine-Modified HK-2 Cell Membrane Chromatography and Screening of Active Components fromInternational journal of molecular sciences · 2024Article
- The impact of solute carrier proteins on disrupting substance regulation in metabolic disorders: insights and clinical applications.Frontiers in pharmacology · 2024Review
- Virtual screening and activity evaluation of human uric acid transporter 1 (hURAT1) inhibitors.RSC advances · 2023Article
- The Mechanism of Sodium-Glucose Cotransporter-2 Inhibitors in Reducing Uric Acid in Type 2 Diabetes Mellitus.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Review
- Hypouricemia and Urate Transporters.Biomedicines · 2022Review
- Genetic epidemiological analysis of hypouricaemia from 4993 Japanese on non-functional variants of URAT1/SLC22A12 gene.Rheumatology (Oxford, England) · 2022Article
- Article
- A Proposal for Practical Diagnosis of Renal Hypouricemia: Evidenced from Genetic Studies of Nonfunctional Variants ofBiomedicines · 2021Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
Abstract
objectivesGout, caused by chronic elevation of serum uric acid levels, is the commonest form of inflammatory arthritis. The causative effect of common and rare variants of ATP-binding cassette transporter G2 (ABCG2/BCRP) on gout risk has been studied, but little attention has been paid to the effect of common (rs121907892, p.W258X) and rare variants of urate transporter 1 (URAT1/SLC22A12) on gout, despite dysfunctional variants of URAT1 having been identified as pathophysiological causes of renal hypouricaemia.
methodsTo address this important but overlooked issue, we investigated the effects of these URAT1 variants on gout susceptibility, using targeted exon sequencing on 480 clinically defined gout cases and 480 controls of Japanese males in combination with a series of functional analyses of newly identified URAT1 variants.
resultsOur results show that both common and rare dysfunctional variants of URAT1 markedly decrease the risk of gout (OR 0.0338, reciprocal OR 29.6, P = 7.66 × 10-8). Interestingly, we also found that the URAT1-related protective effect on gout eclipsed the ABCG2-related causative effect (OR 2.30-3.32). Our findings reveal only one dysfunctional variant of URAT1 to have a substantial anti-gout effect, even in the presence of causative variants of ABCG2, a 'gout gene'.
conclusionOur findings provide a better understanding of gout/hyperuricaemia and its aetiology that is highly relevant to personalized health care. The substantial anti-gout effect of common and rare variants of URAT1 identified in the present study support the genetic concept of a 'Common Disease, Multiple Common and Rare Variant' model.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.