Genetic background of uric acid metabolism in a patient with severe chronic tophaceous gout

Petrů, Lenka; Pavelcová, Kateřina; Šebesta, Ivan; Stibůrková, Blanka

doi:10.1016/j.cca.2016.06.007

Cited by 17 publications

(6 citation statements)

References 15 publications

(9 reference statements)

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“…The animal model of Abcg2-knockout mice showed increased serum urate and renal urate excretion and decreased intestinal urate excretion [12]. Moreover, a significant association between the common variant p.Q141K and an increased risk of a poor response to allopurinol has been described [29–31].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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BackgroundABCG2 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.MethodThe 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.ResultsIn 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).ConclusionOur 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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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“…Secondly, information about risk alleles could help to predict the adverse effects of drugs. For instance, researchers found that the Q141K allele (rs2231142 allele T) conferred a significantly increased risk of poor response to allopurinol (Petru et al, 2016, ZhangSun andShi, 2018. Thirdly, ABCG2 variants have also been associated with tophaceous disease in people with gout.…”

Section: Discussionmentioning

confidence: 99%

Risk Factor Analysis for Gout in the Latvian Population

Nagle

Luksa

Moisejevs

et al. 2020

Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences.

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Communicated by Aivars LejnieksGout (Gr. podagra) is a multifactorial pathology, which means that both genetic and environmental factors play a role in the aetiology of the disease. For these reasons, revealing risk factors could be of very high importance in prevention and treatment of gout. In the present study, we found that a major role in gout predisposition is played by specific alleles in the ABCG2 gene. The study used survey data for 43 gout patients and 99 healthy control individuals who were genotyped for rs2231142. It was found that allelic variant rs2231142 in the ABCG2 gene had the strongest association with gout. Among other co-factors studied, sex, and increased body mass index were associated with gout.

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“…Thus, no patients in our series presented allopurinol resistance or needed allopurinol doses >300 mg/day to achieve the goal serum uric acid level. Two patients with HPRT deficiency have been reported in whom genotyping of the ABCG2 , URAT1 and GLUT9 SNPs had been performed . In these patients, a heterozygous CA genotype for ABCG2 rs2231142 was associated with a poor response to xanthine oxidase inhibition.…”

Section: Discussionmentioning

confidence: 99%