Common variant of leucine-rich repeat-containing 16A (LRRC16A) gene is associated with gout susceptibility.
Common variant of leucine-rich repeat-containing 16A (LRRC16A) gene is associated with gout susceptibility.
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DOI：
10.1007/s13577-013-0081-8
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发表时间：
2014-01
期刊：
影响因子：
4.3
通讯作者：
Shinomiya, Nariyoshi
中科院分区：
文献类型：
--
作者：
Sakiyama, Masayuki;Matsuo, Hirotaka;Shimizu, Seiko;Chiba, Toshinori;Nakayama, Akiyoshi;Takada, Yuzo;Nakamura, Takahiro;Takada, Tappei;Morita, Emi;Naito, Mariko;Wakai, Kenji;Inoue, Hiroki;Tatsukawa, Seishiro;Sato, Junki;Shimono, Kazumi;Makino, Toshiaki;Satoh, Takahiro;Suzuki, Hiroshi;Kanai, Yoshikatsu;Hamajima, Nobuyuki;Sakurai, Yutaka;Ichida, Kimiyoshi;Shimizu, Toru;Shinomiya, Nariyoshi
关键词：
痛风是由高尿酸血症引起的急性关节炎的常见疾病。最近，全基因组关联研究揭示了血清尿酸水平与富含亮氨酸重复序列的 16A (LRRC16A) 基因的常见变体之间的关联。然而，LRRC16A是否会导致痛风易感性仍有待澄清。在本研究中，我们研究了LRRC16A中的rs742132与痛风之间的关系。对总共 545 名日本男性痛风病例和 1,115 名作为对照组的男性个体进行了基因分型。 rs742132 A/A 基因型显着增加痛风风险，比值比为 1.30 (95% CI 1.05–1.60；p = 0.015)。 LRRC16A 编码一种称为加帽蛋白 ARP2/3 和肌球蛋白-I 连接子 (CARMIL) 的蛋白质，它充当肌动蛋白加帽蛋白 (CP) 的抑制剂。 CP 是肌动蛋白细胞骨架的重要元素，它与肌动蛋白丝的有刺末端结合并调节其聚合。在人肾近端肾小管细胞的顶膜中，尿酸盐转运多分子复合物（尿酸盐转运体）被认为由几种尿酸盐转运蛋白和支架蛋白组成，它们与肌动蛋白细胞骨架相互作用。因此，如果肌动蛋白聚合中存在 CARMIL 功能障碍和调节障碍，尿酸转运体可能无法正常运行。我们首次证明 CARMIL/LRRC16A 与痛风相关，这可能是由于尿酸盐转运体故障所致。本文的在线版本 (doi:10.1007/s13577-013-0081-8) 包含补充材料，可供授权用户使用。
Gout is a common disease resulting from hyperuricemia which causes acute arthritis. Recently, genome-wide association studies revealed an association between serum uric acid levels and a common variant of leucine-rich repeat-containing 16A (LRRC16A) gene. However, it remains to be clarified whether LRRC16A contributes to the susceptibility to gout. In this study, we investigated the relationship between rs742132 in LRRC16A and gout. A total of 545 Japanese male gout cases and 1,115 male individuals as a control group were genotyped. rs742132 A/A genotype significantly increased the risk of gout, conferring an odds ratio of 1.30 (95 % CI 1.05–1.60; p = 0.015). LRRC16A encodes a protein called capping protein ARP2/3 and myosin-I linker (CARMIL), which serves as an inhibitor of the actin capping protein (CP). CP is an essential element of the actin cytoskeleton, which binds to the barbed end of the actin filament and regulates its polymerization. In the apical membrane of proximal tubular cells in the human kidney, the urate-transporting multimolecular complex (urate transportsome) is proposed to consist of several urate transporters and scaffolding proteins, which interact with the actin cytoskeleton. Thus, if there is a CARMIL dysfunction and regulatory disability in actin polymerization, urate transportsome may be unable to operate appropriately. We have shown for the first time that CARMIL/LRRC16A was associated with gout, which could be due to urate transportsome failure. The online version of this article (doi:10.1007/s13577-013-0081-8) contains supplementary material, which is available to authorized users.
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影响因子：
4.5
作者：
Qayyum R;Snively BM;Ziv E;Nalls MA;Liu Y;Tang W;Yanek LR;Lange L;Evans MK;Ganesh S;Austin MA;Lettre G;Becker DM;Zonderman AB;Singleton AB;Harris TB;Mohler ER;Logsdon BA;Kooperberg C;Folsom AR;Wilson JG;Becker LC;Reiner AP
通讯作者：
Reiner AP
影响因子：
4.6
作者：
Matsuo H;Ichida K;Takada T;Nakayama A;Nakashima H;Nakamura T;Kawamura Y;Takada Y;Yamamoto K;Inoue H;Oikawa Y;Naito M;Hishida A;Wakai K;Okada C;Shimizu S;Sakiyama M;Chiba T;Ogata H;Niwa K;Hosoyamada M;Mori A;Hamajima N;Suzuki H;Kanai Y;Sakurai Y;Hosoya T;Shimizu T;Shinomiya N
通讯作者：
Shinomiya N
影响因子：
16.6
作者：
通讯作者：
--
影响因子：
4.1
作者：
Margraf, Rebecca L.;Mao, Rong;Wittwer, Carl T.
通讯作者：
Wittwer, Carl T.
影响因子：
3.7
作者：
Stark K;Reinhard W;Grassl M;Erdmann J;Schunkert H;Illig T;Hengstenberg C
通讯作者：
Hengstenberg C