Genetic polymorphisms and decreased protein expression of ABCG2 urate transporters are associated with susceptibility to gout, disease severity and renal-overload hyperuricemia

Clinical and Experimental Medicine · 12 authors, 4 centres

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TL;DR

Genotyping targeted four functional SNPs (Q141K, M71V, R236X, R383C).

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Genotyping targeted four functional SNPs (Q141K, M71V, R236X, R383C). The authors found that 32.1% of gout patients carried at least one studied SNP compared to 13.7% of controls, yielding an odds ratio of 3.0 for gout risk. Patients with functional polymorphisms presented gout approximately 8 years earlier than wild-type patients. Frequent flares were independently associated with the presence of ABCG2 SNPs. Decreased RBC-ABCG2 protein expression was significantly associated with functional polymorphisms, particularly the M71V variant. Both altered protein levels and genetic changes correlated with elevated fractional and urinary urate excretion, consistent with renal-overload hyperuricemia. Limitations include relatively modest sample size, self-reported dietary and hydration control, and absence of comorbidity assessment.

STUDY TYPE

case-control

SPECIALTY

rheumatology

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ORIGINAL PAPER

PMC10390358

Genetic polymorphisms and decreased protein expression of ABCG2 urate transporters are associated with susceptibility to gout, disease severity and renal-overload hyperuricemia

Clinical and Experimental Medicine

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ABSTRACT

Abstract Gout is a common crystal induced disease of high personal and social burden, characterised by severe arthritis and comorbidity if untreated. Impaired function of ABCG2 transporter is causative in gout and may be responsible for renal-overload type hyperuricemia. Despite its importance, there is limited information on how clinical parameters correlate with protein expression and that with genetic changes. Urate and clinical parameters of 78 gouty patients and healthy controls were measured among standardised circumstances from a Hungarian population. ABCG2 membrane expression of red blood cells was determined by flow cytometry-based method and SNPs of this protein were analysed by TaqMan-based qPCR. The prevalence of ABCG2 functional polymorphisms in gouty and control patients were 32.1 and 13.7%, respectively. Most common SNP was Q141K while one sample with R236X, R383C and the lately described M71V were found in the gouty population. These polymorphisms showed strong linkage with decreased protein expression while the latter was also associated with higher fractional urate excretion (FUE) and urinary urate excretion (UUE). This study firstly evaluated ABCG2 protein expression in a clinically defined gouty population while also proving its associations between ABCG2 genetic changes and renal-overload hyperuricemia. The paper also highlighted relations between ABCG2 SNPs, gout susceptibility and disease severity characterised by an early onset disease with frequent flares and tophi formation. Keywords: ABCG2 transporters, Genetics, Protein expression, Gout severity, Renal-overload hyperuricemia

CITATION EXPORT

Márton Pálinkás, Edit Szabó, Anna Kulin et al.. Genetic polymorphisms and decreased protein expression of ABCG2 urate transporters are associated with susceptibility to gout, disease severity and renal-overload hyperuricemia. Clinical and Experimental Medicine. (2022). https://doi.org/10.1007/s10238-022-00848-7

AUTHORS

12 · 4 CENTRES

Márton Pálinkás, Edit Szabó, Anna Kulin, Orsolya Mózner, Rita Rásonyi, Péter Juhász, Krisztina Nagy, György Várady, Dóra Vörös, Boglárka Zámbó, Balázs Sarkadi, Gyula Poór

1National Institute of Locomotor Diseases and Disabilities, Frankel Leo str. 38-40, 1023 Budapest, Hungary
2Doctoral School of Molecular Medicine, Semmelweis University, Budapest, Hungary
3Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary
4Section of Rheumatology and Physiotherapy, Department of Internal Medicine and Haematology, Semmelweis University, Budapest, Hungary