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尿酸相关基因LRP2的常见变异与痛风易感性无关。

Common variants of a urate-associated gene LRP2 are not associated with gout susceptibility.

作者信息

Nakayama Akiyoshi, Matsuo Hirotaka, Shimizu Toru, Takada Yuzo, Nakamura Takahiro, Shimizu Seiko, Chiba Toshinori, Sakiyama Masayuki, Naito Mariko, Morita Emi, Ichida Kimiyoshi, Shinomiya Nariyoshi

机构信息

Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.

出版信息

Rheumatol Int. 2014 Apr;34(4):473-6. doi: 10.1007/s00296-013-2924-8. Epub 2013 Dec 24.

Abstract

A recent genome-wide association study revealed that there is an association between serum uric acid (SUA) levels and rs2544390, a common variant in low-density lipoprotein-related protein 2 (LRP2/Megalin) gene. Two other variants of LRP2, rs2229268 and rs3755166, are also found to have associations with dyslipidemia and Alzheimer's disease, respectively, which also could have a relationship with SUA in human. Although no studies report that LRP2 transports urate, LRP2 is a multi-ligand receptor and expresses in many tissues including kidney, suggesting a direct and/or indirect relationship with gout. In the present study, we investigated the association between gout and these variants of LRP2 with 741 clinically diagnosed male gout patients and 1,302 controls. As a result, the three common LRP2 variants, rs2544390, rs2229268 and rs3755166, showed no association with gout (P = 0.76, 0.55, and 0.22, respectively). Our study is the first to reveal that an SUA-related gene LRP2 is not involved in gout susceptibility.

摘要

最近一项全基因组关联研究表明,血清尿酸(SUA)水平与低密度脂蛋白相关蛋白2(LRP2/巨膜蛋白)基因中的常见变异体rs2544390之间存在关联。LRP2的另外两个变异体rs2229268和rs3755166,也分别被发现与血脂异常和阿尔茨海默病有关,这在人类中也可能与SUA存在关联。尽管尚无研究报道LRP2转运尿酸,但LRP2是一种多配体受体,在包括肾脏在内的许多组织中表达,提示其与痛风存在直接和/或间接关系。在本研究中,我们纳入741例临床诊断的男性痛风患者和1302例对照,调查痛风与LRP2这些变异体之间的关联。结果显示,LRP2的三个常见变异体rs2544390、rs2229268和rs3755166与痛风均无关联(P值分别为0.76、0.55和0.22)。我们的研究首次揭示,与SUA相关的基因LRP2不参与痛风易感性。

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