Background/Purpose: The ABCG2 Q141K (rs2231142) variant is an established cause of hyperuricaemia in Europeans. Although the effect size of rs2231142 on serum urate levels is ~60% that of SLC2A9, its effect 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.
Methods: There were 1,672 European gout cases and 15,367 controls and 1,197 New Zealand Polynesian gout cases and 1,371 controls, with Polynesian divided into Eastern (EP) and Western Polynesian (WP). Association testing was performed using logistic regression with adjustment for confounding variables.
Results: In European, the 141K allele was strongly associated with asymptomatic hyperuricemia compared to normouricemic controls (OR=1.55, P=4.3x10-18), and with gout compared to asymptomatic hyperuricemia controls (OR=1.83, P=2.6x10-14). In Polynesian, 141K was not associated with asymptomatic hyperuricemia compared to normouricemic controls (P>0.35), whereas there was a strong risk for gout compared to asymptomatic hyperuricemia (WP: OR=2.35, P=3.9x10-5; EP: OR=2.15, P=0.010). In comparison, SLC2A9 rs11942223 showed no positive association with gout compared with asymptomatic hyperuricemia in European (OR=0.82, P=0.022), WP (OR=0.81, P=0.69) or 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. In Polynesian people, 141K does not play a role in determining hyperuricemia.