BACKGROUND The ABCG2 Q141K (rs2231142) and rs10011796 variants associate with hyperuricaemia (HU). The effect size of ABCG2 rs2231142 on urate is ~ 60% that of SLC2A9, yet the effect size on gout is greater. We tested the hypothesis that ABCG2 plays a role in the progression from HU to gout by testing for association of ABCG2 rs2231142 and rs10011796 with gout using HU controls. METHODS We analysed 1699 European gout cases and 14,350 normouricemic (NU) and HU controls, and 912 New Zealand (NZ) Polynesian (divided into Eastern and Western Polynesian) gout cases and 696 controls. Association testing was performed using logistic and linear regression with multivariate adjusting for confounding variables. RESULTS In Europeans and Polynesians, the ABCG2 141K (T) allele was associated with gout using HU controls (OR = 1.85, P = 3.8E- 21 and ORmeta = 1.85, P = 1.3E- 03, respectively). There was evidence for an effect of 141K in determining HU in European (OR = 1.56, P = 1.7E- 18) but not in Polynesian (ORmeta = 1.49, P = 0.057). For SLC2A9 rs11942223, the T allele associated with gout in the presence of HU in European (OR = 1.37, P = 4.7E- 06), however significantly weaker than ABCG2 rs2231142 141K (PHet = 0.0023). In Western Polynesian and European, there was epistatic interaction between ABCG2 rs2231142 and rs10011796. Combining the presence of the 141K allele with the rs10011796 CC-genotype increased gout risk, in the presence of HU, 21.5-fold in Western Polynesian (P = 0.009) and 2.6-fold in European (P = 9.9E- 06). The 141K allele of ABCG2 associated with increased gout flare frequency in Polynesian (Pmeta = 2.5E- 03). CONCLUSION These data are consistent with a role for ABCG2 141K in gout in the presence of established HU.

中文翻译：

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ABCG2基因在痛风中的多效性：参与血清尿酸水平和从高尿酸血症发展到痛风。

背景ABCG2 Q141K（rs2231142）和rs10011796变体与高尿酸血症（HU）相关。ABCG2 rs2231142对尿酸盐的作用大小约为SLC2A9的60％，但对痛风的作用大小更大。通过使用HU对照测试ABCG2 rs2231142和rs10011796与痛风的关联，我们测试了ABCG2在从HU到痛风的过程中起作用的假设。方法我们分析了1699例欧洲痛风病例和14,350例正常尿毒症（NU）和HU对照，以及912例新西兰（NZ）玻利尼西亚人（分为东西波利尼西亚）痛风病例和696例对照。关联测试使用逻辑和线性回归进行，并针对混杂变量进行了多元调整。结果在欧洲人和波利尼西亚人中，使用HU对照（OR = 1.85，P = 3.8E-21和ORmeta = 1），ABCG2 141K（T）等位基因与痛风相关。85，分别为P = 1.3E-03）。有证据显示，在欧洲（OR = 1.56，P = 1.7E-18）中，141K可以确定HU，但在波利尼西亚人中，则无141K（ORmeta = 1.49，P = 0.057）。对于SLC2A9 rs11942223，欧洲存在HU的情况下与痛风相关的T等位基因（OR = 1.37，P = 4.7E-06），但是比ABCG2 rs2231142 141K弱（PHet = 0.0023）。在波利尼西亚西部和欧洲，ABCG2 rs2231142和rs10011796之间存在上位相互作用。在存在HU的情况下，将141K等位基因与rs10011796 CC基因型结合使用可增加痛风风险，在西玻里尼西亚人中为21.5倍（P = 0.009），在欧洲人中为2.6倍（P = 9.9E-06）。在波利尼西亚，ABCG2的141K等位基因与痛风发作频率增加相关（Pmeta = 2.5E-03）。