Organic anion transporter 10 (OAT10), also known as SLC22A13, has hitherto been identified as a urate transporter by in vitro analyses.1 Despite the reported expression of OAT10 on the apical membrane of the renal proximal tubular cells,1 the physiological impact of OAT10 on urate handling in humans remains to be elucidated. Accumulating evidence suggests that functional variants of already-characterised, physiologically important urate transporters—URAT1/SLC22A12, GLUT9/SLC2A9, BCRP/ABCG2 and NPT1/SLC17A1—affect serum uric acid (SUA) levels and susceptibility of gout,2–6 the most common form of inflammatory arthritis. However, there are no reports on the association between OAT10 gene and either hyperuricaemia or gout. Here, for the first time, we reveal that a dysfunctional variant of OAT10 decreases both gout risk and SUA levels, suggesting OAT10 to be physiologically involved in urate reabsorption in the human kidney, as described below. To explore exonic variants in OAT10 potentially associated with gout susceptibility, we sequenced all exons of OAT10 in 480 gout cases and 480 controls of Japanese male6 and conducted an association analysis (see online supplementary tables S1 and S2), followed by a replication study on 924 gout cases and 2113 controls (see online supplementary figure S1). In two identified OAT10 variants with minor allele frequency (MAF) >0.5%, only rs117371763 (c.1129C>T; p.Arg377Cys [R377C]) was significantly associated with gout susceptibility after Bonferroni correction (p=0.014). The significant association between rs117371763 and gout susceptibility was replicated, and our meta-analysis showed a significant protective effect of rs117371763 on gout susceptibility (OR=0.67; 95% CI 0.53 to 0.85; pmeta …

中文翻译：

---

OAT10/SLC22A13 的功能失调性错义变体降低痛风风险和血清尿酸水平

有机阴离子转运蛋白 10 (OAT10)，也称为 SLC22A13，迄今为止已通过体外分析确定为尿酸盐转运蛋白 1。 尽管据报道 OAT10 在肾近端肾小管细胞的顶膜上表达 1，但 OAT10 的生理影响人体中的尿酸处理仍有待阐明。越来越多的证据表明，已经表征的、生理上重要的尿酸转运蛋白的功能变异体——URAT1/SLC22A12、GLUT9/SLC2A9、BCRP/ABCG2 和 NPT1/SLC17A1——对血清尿酸 (SUA) 水平和痛风的易感性影响最大，2-6炎性关节炎的常见形式。然而，没有关于 OAT10 基因与高尿酸血症或痛风之间关联的报道。在这里，我们首次揭示了 OAT10 功能失调的变体降低了痛风风险和 SUA 水平，表明 OAT10 在生理上参与人体肾脏中的尿酸重吸收，如下所述。为了探索 OAT10 中可能与痛风易感性相关的外显子变异，我们对 480 名痛风病例和 480 名日本男性 6 的对照中的 OAT10 的所有外显子进行了测序，并进行了关联分析（参见在线补充表 S1 和 S2），然后对 924痛风病例和 2113 对照（见在线补充图 S1）。在两个确定的 OAT10 变体中，次要等位基因频率 (MAF) > 0.5%，只有 rs117371763 (c.1129C>T；p.Arg377Cys [R377C]) 与 Bonferroni 校正后的痛风易感性显着相关 (p=0.014)。重复了 rs117371763 与痛风易感性之间的显着关联，