Dysfunctional variants of ATP-binding cassette transporter subfamily G member 2 (ABCG2), a urate transporter in the kidney and intestine, are the major causes of hyperuricemia and gout. A recent study found that ABCG2 is a major transporter of uremic toxins; however, few studies have investigated the relationship between ABCG2 gene polymorphisms and mortality. This prospective cohort study of 1214 hemodialysis patients investigated the association between serum uric acid levels and ABCG2 genotype and mortality. Genotyping of dysfunctional ABCG2 variants, Q126X (rs72552713) and Q141K (rs2231142), was performed using the patients’ DNA. During the study period, 220 patients died. Lower serum uric acid levels were associated with higher mortality (hazard ratio [HR] 1.89, 95% confidence interval [CI] 1.14–3.10, P ≤ 0.001). ABCG2 dysfunction, estimated by genetic variants, had a significant positive association with serum uric acid levels (full function: 7.4 ± 1.2 mg/dl, 3/4 function: 7.9 ± 1.3 mg/dl, 1/2 function: 8.2 ± 1.4 mg/dl, ≤ 1/4 function: 8.7 ± 1.3 mg/dl, P ≤ 0.001). This association remained significant on multiple regression analysis. The Cox proportional hazard analysis indicated that the ABCG2 ≤ 1/4 function type was significantly associated with higher mortality (HR 6.66, 95% CI 2.49 to 17.8, P ≤ 0.001) than the other function types. These results showed that ABCG2 plays a physiologically important role in uric acid excretion, and that ABCG2 dysfunction is a risk factor for mortality in hemodialysis patients.

中文翻译：

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功能异常的ABCG2基因多态性与血液透析患者的血清尿酸水平和全因死亡率有关。

ATP结合盒转运蛋白亚家族G成员2（ABCG2）（肾和肠中的尿酸盐转运蛋白）的功能异常变体是高尿酸血症和痛风的主要原因。最近的一项研究发现，ABCG2是尿毒症毒素的主要转运蛋白。但是，很少有研究调查ABCG2基因多态性与死亡率之间的关系。这项针对1214名血液透析患者的前瞻性队列研究调查了血清尿酸水平与ABCG2基因型和死亡率之间的关系。使用患者的DNA对功能异常的ABCG2变体Q126X（rs72552713）和Q141K（rs2231142）进行基因分型。在研究期间，有220名患者死亡。较低的血清尿酸水平与较高的死亡率相关（危险比[HR] 1.89，95％置信区间[CI] 1.14–3.10，P ≤0.001）。通过基因变异估计的ABCG2功能异常与血清尿酸水平呈显着正相关（全功能：7.4±1.2 mg / dl，3/4功能：7.9±1.3 mg / dl，1/2功能：8.2±1.4 mg / dl时，≤1/4函数：8.7±1.3毫克/分升，P  ≤0.001）。这种关联在多元回归分析中仍然很重要。Cox比例风险分析表明，ABCG2≤1/4函数类型是显著与较高的死亡率（HR 6.66; 95％CI 2.49至17.8，P  ≤0.001）比其它函数类型。这些结果表明，ABCG2在尿酸排泄中起着重要的生理作用，而ABCG2功能障碍是血液透析患者死亡的危险因素。