Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: The ABCG2 Q141K (rs2231142) variant is an established cause of hyperuricaemia in Europeans. Although the effect size of ABCG2 rs2231142 on serum urate levels is ~60% that of SLC2A9, the effect size of ABCG2 on gout is consistently greater than that of SLC2A91,2. We tested the hypothesis that ABCG2 plays a role in gout additional to causing hyperuricemia by testing for association of rs2231142 with gout using asymptomatic hyperuricemic controls. SLC2A9 rs11942223 was included for comparison.
Methods: There were 1,672 European gout cases and 15,367 controls and 1,197 New Zealand Polynesian (Māori and Pacific Island) gout cases and 1,371 controls. The Polynesian sample set was divided into Eastern (EP) and Western Polynesian (WP). Association testing was done using logistic regression with multivariate adjusting for confounding variables, including highest recorded serum urate in analyses with gout cases.
Results: In the European sample set, the 141K allele was strongly associated with asymptomatic hyperuricemia compared with normouricemic controls (OR=1.55, P=4.3×10-18) and with gout compared with asymptomatic hyperuricemia controls (OR=1.83, P=2.6×10-14). In the Polynesian sample sets, the 141K variant was not associated with asymptomatic hyperuricemia compared with normouricemic controls (WP: OR=1.22, P=0.35; EP: OR=0.99, P=0.97) whereas there was a strong risk effect for gout compared with asymptomatic hyperuricemia (WP: OR=2.35, P=3.9×10-5; EP: OR=2.15, P=0.010). For SLC2A9 rs11942223, there was no positive association with gout compared with asymptomatic hyperuricemia controls in any of the ancestral sample sets (Europeans: OR=0.82, P=0.022; WP: OR=0.81, P=0.69 and EP: OR=1.39, P=0.41).
Conclusion: These data are consistent with a role for ABCG2 141K in gout pathogenesis when hyperuricemia is established, potentially through formation of monosodium urate crystals and/or regulation of the inflammatory response to deposited crystals. In Polynesian people ABCG2 141K does not play a role in determining hyperuricemia. 1. Kottgen et al. Nat Genet 2013;45:145-54. 2. Phipps-Green et al. Ann Rheum Dis 2016;75:124-30.
To cite this abstract in AMA style:Merriman TR, Phipps-Green A, Boocock J, Riches P, Tausche AK, Radstake T, Janssen M, Joosten LAB, Jansen TL, So A, Harre Hindmarsh J, Stamp LK, Dalbeth N, Wrigley R. Pleiotropic Effect of ABCG2 in Gout [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/pleiotropic-effect-of-abcg2-in-gout/. Accessed November 21, 2019.
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