Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Common dysfunctional variants of ABCG2, a high-capacity urate transporter gene, that result in decreased urate excretion, are major causes of hyperuricemia and gout. In the present study, we describe the first detailed analysis of disease-relevant functional allelic variants in the ABCG2 gene.
The main cohort recruited from the Czech Republic consisted of 155 gout patients, 115 normouricemic controls were used for comparison. We amplified, directly sequenced, and analyzed 15 ABCG2 exons. The associations between genetic variants and clinical phenotype were analyzed using the t-test, Fisher exact test and logistic and linear regression approach. Data from a NZ Polynesian sample set and the UK Biobank were included for the p.V12M analysis.
In the ABCG2 gene, 18 intronic (one dysfunctional splicing1) and 12 exonic variants were detected: 10 were non-synonymous (two common, eight rare including one novel): p.V12M, p.Q141K, p.R147W, p.T153M, p.F373C, p.T434M, p.S476P, p.S572R, p.D620N, and p.K360del. The p.Q141K (rs2231142) variant had a significantly higher minor allele frequency (0.23) in the gout patients compared to the European-origin population (0.09) and was significantly more common among gout patients than among normouricemic controls (OR = 3.15, p<0.0001). Patients with non-synonymous allelic variants had an earlier onset of gout (41.5 vs. 48 years, p=0.0478) and a greater likelihood of a familial history of gout (42% vs. 26%, OR = 2.02, p=0.043). In a meta-analysis p.V12M exerted a protective effect from gout (p<0.0001).
Genetic variants of ABCG2, common and rare, increased the risk of gout. Non-synonymous allelic variants of ABCG2 had a significant effect on earlier onset of gout and the presence of a familial gout history. ABCG2 should thus be considered a common and significant risk factor for gout.
1. Stiburkova B, Miyata H, Závada J, Tomčík M, Pavelka K, Storkanova G, Toyoda Y, Takada T, Suzuki H. Novel dysfunctional variant in ABCG2 as a cause of severe tophaceous gout: biochemical, molecular genetics and functional analysis. Rheumatology (Oxford). 2016 Jan;55(1):191-4.
This study was supported by the grants from the Czech Republic Ministry of Health AZV 15-26693A.
To cite this abstract in AMA style:Stiburkova B, Pavelcova K, Zavada J, Petru L, Pavlikova M, Matsuo H, Merriman TR, Pavelka K. Allelic Variants of ABCG2 and Gout Risk [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/allelic-variants-of-abcg2-and-gout-risk/. Accessed September 20, 2021.
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