Common missense variant of monocarboxylate transporter 9 (MCT9/SLC16A9) gene is associated with renal overload gout, but not with all gout susceptibility.
Common missense variant of monocarboxylate transporter 9 (MCT9/SLC16A9) gene is associated with renal overload gout, but not with all gout susceptibility.
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DOI：
10.1007/s13577-013-0073-8
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发表时间：
2013-12
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：
Nakayama, Akiyoshi;Matsuo, Hirotaka;Shimizu, Takuya;Ogata, Hiraku;Takada, Yuzo;Nakashima, Hiroshi;Nakamura, Takahiro;Shimizu, Seiko;Chiba, Toshinori;Sakiyama, Masayuki;Ushiyama, Chisaki;Takada, Tappei;Inoue, Katsuhisa;Kawai, Sayo;Hishida, Asahi;Wakai, Kenji;Hamajima, Nobuyuki;Ichida, Kimiyoshi;Sakurai, Yutaka;Kato, Yukio;Shimizu, Toru;Shinomiya, Nariyoshi
关键词：
痛风是一种常见的高尿酸血症引起的疾病，表现为血清尿酸（SUA）水平升高。从人的尿酸盐处理的观点来看，痛风患者可分为具有肠尿酸盐排泄不足的肾超负荷（ROL）痛风患者和具有肾排泄不足（芸香）痛风患者。最近的全基因组关联研究（GWAS）显示SUA与人类单羧酸转运蛋白9（MCT 9/SLC 16 A9）基因的变异相关。尽管MCT 9的功能尚不清楚，但尿酸盐主要通过肠道和肾脏排泄，在肠道和肾脏中观察到MCT 9表达。在这项研究中，我们调查了545名患者和1，115名健康志愿者的MCT 9变体与痛风之间的关系。MCT 9（K258 T）的错义变体rs 2242206显著增加了ROL痛风的风险（p = 0.012），比值比（OR）为1.28，尽管它与所有痛风病例（p = 0.10），非ROL痛风病例（p = 0.83）和芸香痛风病例（p = 0.34）无显著相关性。在任何病例组和对照组中，rs 2242206的次要等位基因频率均>0.40。因此，rs 2242206是一种常见的错义变体，并显示与ROL痛风相关，表明rs 2242206与肠道尿酸盐排泄减少有关，而不是肾尿酸盐排泄减少。我们的研究为更好地了解痛风的病理生理学以及MCT 9的生理作用提供了线索。
Gout is a common disease caused by hyperuricemia, which shows elevated serum uric acid (SUA) levels. From a viewpoint of urate handling in humans, gout patients can be divided into those with renal overload (ROL) gout with intestinal urate underexcretion, and those with renal underexcretion (RUE) gout. Recent genome-wide association studies (GWAS) revealed an association between SUA and a variant in human monocarboxylate transporter 9 (MCT9/SLC16A9) gene. Although the function of MCT9 remains unclear, urate is mostly excreted via intestine and kidney where MCT9 expression is observed. In this study, we investigated the relationship between a variant of MCT9 and gout in 545 patients and 1,115 healthy volunteers. A missense variant of MCT9 (K258T), rs2242206, significantly increased the risk of ROL gout (p = 0.012), with odds ratio (OR) of 1.28, although it revealed no significant association with all gout cases (p = 0.10), non-ROL gout cases (p = 0.83), and RUE gout cases (p = 0.34). In any case groups and the control group, minor allele frequencies of rs2242206 were >0.40. Therefore, rs2242206 is a common missense variant and is revealed to have an association with ROL gout, indicating that rs2242206 relates to decreased intestinal urate excretion rather than decreased renal urate excretion. Our study provides clues to better understand the pathophysiology of gout as well as the physiological roles of MCT9.
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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：
1.9
作者：
Gunjaca, Grgo;Boban, Mladen;Polasek, Ozren
通讯作者：
Polasek, Ozren
影响因子：
4.5
作者：
Kolz M;Johnson T;Sanna S;Teumer A;Vitart V;Perola M;Mangino M;Albrecht E;Wallace C;Farrall M;Johansson A;Nyholt DR;Aulchenko Y;Beckmann JS;Bergmann S;Bochud M;Brown M;Campbell H;EUROSPAN Consortium;Connell J;Dominiczak A;Homuth G;Lamina C;McCarthy MI;ENGAGE Consortium;Meitinger T;Mooser V;Munroe P;Nauck M;Peden J;Prokisch H;Salo P;Salomaa V;Samani NJ;Schlessinger D;Uda M;Völker U;Waeber G;Waterworth D;Wang-Sattler R;Wright AF;Adamski J;Whitfield JB;Gyllensten U;Wilson JF;Rudan I;Pramstaller P;Watkins H;PROCARDIS Consortium;Doering A;Wichmann HE;KORA Study;Spector TD;Peltonen L;Völzke H;Nagaraja R;Vollenweider P;Caulfield M;WTCCC;Illig T;Gieger C
通讯作者：
Gieger C