Introduction The urate transporters are one of the main genetic determinants of serum uric acid concentrations. Primarily nonsynonymous polymorphisms in ABCG2 and SLC2A9 are clinically important for the development of primary gout and hyperuricemia. In this study we investigated the effects of allelic variants of urate transporters in a cohort with primary gout and/or hyperuricemia.

Methods The cohort was recruited in the Institute of Rheumatology, gout was diagnosed in 165 subjects (151 men/14 women) and hyperuricemia in 58 subjects (39 men/19 women). Coding regions of ABCG2, SLC2A9, SLC22A11, SLC22A8, SLC17A3, and SLC17A1 genes were amplified and sequenced directly.

Results In ABCG2 gene, we detected nine non-synonymous variants: p.V12M, p.Q141K, p.R147W, p.T153M, p.K360del, p.F373C, p.T434M, p.S476P and p.D620N. The minor allelic frequency of p.Q141K is 0.23, whereas for the European population it is 0.09. In addition, this variant is associated with early onset of the gout.¹ We identified novel intron variant c.689+1G>A which is associated with two abnormal splicing variants, leading to premature introduction of the stop codon.²

In SLC2A9 gene, seven missense variants were identified: p.A17T, p.G25R, p.T275M, p.D281H, p.V282I, p.R294H, and p.P350L. In SLC17A3 gene, the analysis revealed allelic variants p.A100T and p.G279R. Non-synonymous variants p.V202M and p.R343L were found in SLC22A11. Only one missense variant (p.T269I) was identified in SLC17A1. In SLC22A8 gene, sequencing revealed three non-synonymous variants p.R149C, p.V448I and p.R513G.

Conclusions Genetic variants of ABCG2, common and rare, increased the risk of gout. The precise impact of SLC22A11, SLC22A8, SLC17A3, and SLC17A1 in the context of hyperuricemia and gout in our cohort is unclear. Although knowledge of renal urate handling has been increased, current evidence is insufficient to fully understand the precise mechanism governing the bi-directional transport of urate.

References

1. . Stiburkova B, et al. Functional non-synonymous variants of ABCG2 and gout risk. Rheumatology (Oxford)2017November 1;56(11):1982–1992.

2. . Stiburkova B, et al. Novel dysfunctional variant in ABCG2 as a cause of severe tophaceous gout: Biochemical, molecular genetics and functional analysis. Rheumatology (Oxford)2016January;55(1):191–4.

Acknowledgements This study was supported by the grant from the Czech Republic Ministry of Health AZV 15-26693A.

Disclosure of interest None declared