Session Information
Date: Monday, November 13, 2023
Title: (1100–1123) Metabolic & Crystal Arthropathies – Basic & Clinical Science Poster II
Session Type: Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Hyperuricemia is a central feature in the pathogenesis of gout. Hyperuricemia results from an imbalance between endogenous production and excretion of urate; however, the main cause of hyperuricemia is reduced renal excretion of urate. Accumulating evidence suggests that the net amount of excreted uric acid is regulated mainly by urate transporters, such as urate transporter 1 (URAT1, a renal urate re-absorber), solute carrier family 2 member 9 (SLC2A9, also known as glucose transporter member 9), and ATP-binding cassette subfamily G member 2 (ABCG2, which is high capacity urate exporter expressed in the kidneys and intestines). Decreased extra-renal urate excretion caused by ABCG2 dysfunction is a common mechanism of hyperuricemia.
Methods: In both the hyperuricemia and gout Czech subcohort, partly previously described (1, 2) we analyzed genetic variants that are strongly associated with the transition from asymptomatic hyperuricemia to gout (3). 13 independent single nucleotide polymorphisms in ABCG2 (rs2231142, rs131204000, rs7672194), SLC2A9 (rs16890979, rs16891234), SLC22A11 (rs2078267), GCKR (rs1260326), MEPE (rs114580333), PPM1K-DT (rs4693211, rs28793136, rs1545207), LOC105377323 (rs114791459) and ADH1B (rs1229984) were genotyped using direct DNA sequencing with generic sequencing primers by ABI 3130 automated sequencer. The frequencies of polymorphisms were evaluated using Lasergene software and results were compared between a group of patients with primary hyperuricemia and patients with gout and data of the European population from the 1000 Genomes Project.
Results: We are currently completing a genetic analysis of patients with primary hyperuricemia and gout, consisting of more than 450 patients (60% gout patients). Most of the examined variants occur with significantly different frequencies in our cohort of patients with primary hyperuricemia and gout compared to the European population. Variants rs13120400, rs16890979, rs2078267, rs1260326,rs114791459, and rs1229984 showed a significantly lower frequency (p ≤ 0.0001) in our cohort compared to the European. On the contrary, variants rs2231142, rs7672194, rs4693211 (p ≤ 0.0001), rs28793136 (p = 0.0021), and rs114580333 (p = 0.0286) showed a significantly higher frequency in our cohort compared to the European. There was no significant difference in the frequency of these SNPs between the subcohort of patients with primary hyperuricemia and those with gout.
Conclusion: The preliminary results of our study are not entirely consistent with the findings of the GWAS study, which looked for loci associated with asymptomatic hyperuricemia to gout transition and described 13 such SNPs (3). We confirmed only a significantly higher incidence of 5 of these variants in a cohort of patients with primary hyperuricemia/gout, and the frequency of none of the 13 variants differed between subcohorts.
References:
1. Pavelcova K, et al. J Clin Med. 2020 Aug 4;9(8):2510.
2. Horváthová V, et al. J Clin Med. 2019 Nov 14;8(11):1965.
3. Sandoval-Plata G, et al. Ann Rheum Dis. 2021 Sep;80(9):1220-1226.
Funded by: Ministry of Health, Czech Republic, NU22-01-00465.
To cite this abstract in AMA style:
Stiburkova B, Pavelcova K, Masinova J, Pavlikova M, Pavelka K. Genetic Risk Variants in Hyperuricemia and Gout: Common Disease, Multiple Common and Rare Variant Hypothesis [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/genetic-risk-variants-in-hyperuricemia-and-gout-common-disease-multiple-common-and-rare-variant-hypothesis/. Accessed .« Back to ACR Convergence 2023
ACR Meeting Abstracts - https://acrabstracts.org/abstract/genetic-risk-variants-in-hyperuricemia-and-gout-common-disease-multiple-common-and-rare-variant-hypothesis/