Nakayama Akiyoshi, Matsuo Hirotaka, Shimizu Toru, Takada Yuzo, Nakamura Takahiro, Shimizu Seiko, Chiba Toshinori, Sakiyama Masayuki, Naito Mariko, Morita Emi, Ichida Kimiyoshi, Shinomiya Nariyoshi
Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
Rheumatol Int. 2014 Apr;34(4):473-6. doi: 10.1007/s00296-013-2924-8. Epub 2013 Dec 24.
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.
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。