LAUSR

Gouty arthritis, caused by a persistent increase in serum uric acid level, can be caused by underexcretion of uric acid by uric transporters; however, the effects of allelic variants of urate transportosome are yet to be fully determined.In this study we investigated the effects of 10 genes of urate transportosome in a cohort of patients with primary hyperuricemia and gout.The cohort consisted of 114 hyperuricemic individuals; 207 gout patients; and 274 normouricemic controls.We identified 39 non-synonymous allelic variants in the 10 genes of urate transportosome in hyperuricemia/gout cohort. For 22 variants, a European MAF <0.0001 is documented. From the total of 39 identified variants we selected 23 variants for functional characterization based on a) finding of a newly identified variant, b) MAF variant was significantly different in the group of patients with hyperuricemia/gout, c) with high probability, in silico predictions showed devastating influence of variant on protein function.Although further analyzes are needed to elucidate the contribution of urate transportosome to urate homeostasis, our results clearly show that ABCG2 transporter analysis has significant clinical potential. Of the identified non-synonymous allelic variants of the urate transportosome, rs2231142 (p.Q141K) in the ABCG2 gene, proved to be the most clinically significant on the age onset (P < 0.0002, Kruskal-Wallis test).[1]Toyoda Y, et al. Cells. 2019 Apr 18;8(4). 2. Stiburkova B, et al. Rheumatology (Oxford). 2016 Jan;55(1):191-4. 3. Toyoda Y, et al. Arthritis Res Ther. 2019 Oct 28;21(1):219.This study was supported by the grant from the Czech Republic Ministry of Health AZV 15-26693A and RVO 00023728.Blanka Stiburkova: None declared, Katerina Pavelcova: None declared, Jana Bohata: None declared, Marketa Pavlikova: None declared, Tappei Takada: None declared, Yu Toyoda: None declared, Lenka Hasikova: None declared, Jakub Zavada Speakers bureau: Abbvie, UCB, Sanofi, Elli-Lilly, Novartis, Zentiva, Accord, Karel Pavelka Consultant of: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Speakers bureau: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen