Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Mar 20;21(1):77.
doi: 10.1186/s13075-019-1860-8.

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

Blanka Stiburkova  1   2 , Katerina Pavelcova  3   4 , Marketa Pavlikova  3 , Pavel Ješina  5 , Karel Pavelka  3
Affiliations

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

Blanka Stiburkova et al. Arthritis Res Ther. .

Abstract

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.

Keywords: ABCG2; Gout; Hyperuricemia; Urate transport.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Ethics Committee of the Institute of Rheumatology (reference number 6181/2015). All patients and healthy controls were fully informed of the aim of the study, and written informed consent was obtained from all participants.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Differential diagnostic algorithm in a pediatric-onset patient with hyperuricemia. (BMI body mass index, WHR wait to hip ratio, HbA1c glycated hemoglobin, Ca calcium, ALP alkaline phosphatase, SU serum urate, GSD glycogen storage disorders, B blood, U urine, S serum)
Fig. 2
Fig. 2
Genotype frequency of p.Q141K in a pediatric-onset cohort with hyperuricemia/gout (31 subjects, MAF = 38.7%) compared to an adult-onset hyperuricemia/gout (203 subjects, MAF = 21.2%), and a normouricemic control cohort (115 subjects, MAF = 8.5%), and data from the ExAC and 1000 Genome databases
Fig. 3
Fig. 3
a The influence of p.Q141K: homozygotes develop hyperuricemia very early compared to heterozygotes and wild-type homozygotes. b The existence of familial hyperuricemia/gout shifts the age of onset towards earlier ages in the whole set
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007–2008. Arthritis Rheum. 2011;63:3136–3141. doi: 10.1002/art.30520. - DOI - PubMed
    1. Hak AE, Curhan GC, Grodstein F, et al. Menopause, postmenopausal hormone use and risk of incident gout. Ann Rheum Dis. 2010;69(7):1305–1309. doi: 10.1136/ard.2009.109884. - DOI - PMC - PubMed
    1. Harrold LR, Yood RA, Mikuls TR, et al. Sex differences in gout epidemiology: evaluation and treatment. Ann Rheum Dis. 2006;65(10):1368–1372. doi: 10.1136/ard.2006.051649. - DOI - PMC - PubMed
    1. Harrold LR, Etzel CJ, Gibofsky A, et al. Sex differences in gout characteristics: tailoring care for women and men. BMC Musculoskelet Disord. 2017;18(1):108. doi: 10.1186/s12891-017-1465-9. - DOI - PMC - PubMed
    1. Zikánová M, Wahezi D, Hay A, et al. Clinical manifestations and molecular aspects of phosphoribosylpyrophosphate synthetase superactivity in females. Rheumatology (Oxford) 2018;57(7):1180–1185. doi: 10.1093/rheumatology/key041. - DOI - PMC - PubMed

Publication types

MeSH terms