A common missense variant of monocarboxylate transporter 9 (MCT9/SLC16A9) gene is associated with renal overload gout, but not with all gout susceptibility

被引：74

作者：

Nakayama, Akiyoshi ^{[1
,2
]}

Matsuo, Hirotaka ^{[1
]}

Shimizu, Takuya ^{[3
]}

Ogata, Hiraku ^{[1
]}

Takada, Yuzo ^{[4
]}

Nakashima, Hiroshi ^{[5
]}

Nakamura, Takahiro ^{[6
]}

Shimizu, Seiko ^{[1
]}

Chiba, Toshinori ^{[1
]}

Sakiyama, Masayuki ^{[1
]}

Ushiyama, Chisaki ^{[7
]}

Takada, Tappei ^{[8
]}

Inoue, Katsuhisa ^{[9
]}

Kawai, Sayo ^{[10
]}

Hishida, Asahi ^{[11
]}

Wakai, Kenji ^{[10
]}

Hamajima, Nobuyuki ^{[11
]}

Ichida, Kimiyoshi ^{[12
]}

Sakurai, Yutaka ^{[5
]}

Kato, Yukio ^{[3
]}

Shimizu, Toru ^{[13
]}

Shinomiya, Nariyoshi ^{[1
]}

机构：

[1] Natl Def Med Coll, Dept Integrat Physiol & Bionano Med, Tokorozawa, Saitama 3598513, Japan

[2] Japan Air Self Def Force, Iwo To Air Base Grp, Med Grp, Headquarters, Ogasawara, Japan

[3] Kanazawa Univ, Fac Pharm, Inst Med Pharmaceut & Hlth Sci, Kanazawa, Ishikawa, Japan

[4] Natl Def Med Coll, Cent Res Inst, Lab Biofunct, Tokorozawa, Saitama 359, Japan

[5] Natl Def Med Coll, Dept Prevent Med & Publ Hlth, Tokorozawa, Saitama 359, Japan

[6] Natl Def Med Coll, Math Lab, Tokorozawa, Saitama 359, Japan

[7] Toho Univ, Fac Sci, Dept Biol, Funabashi, Chiba 274, Japan

[8] Univ Tokyo, Fac Med, Dept Pharm, Tokyo Univ Hosp, Tokyo 113, Japan

[9] Tokyo Univ Pharm & Life Sci, Sch Pharm, Dept Biopharmaceut, Tokyo, Japan

[10] Nagoya Univ, Dept Prevent Med, Grad Sch Med, Nagoya, Aichi 4648601, Japan

[11] Nagoya Univ, Grad Sch Med, Dept Healthcare Adm, Nagoya, Aichi 4648601, Japan

[12] Tokyo Univ Pharm & Life Sci, Dept Pathophysiol, Tokyo, Japan

[13] Midorigaoka Hosp, Takatsuki, Osaka, Japan

来源：

HUMAN CELL | 2013年 / 26卷 / 04期

基金：

日本学术振兴会;

关键词：

Gouty arthritis; Single nucleotide polymorphism (SNP); Gut urate excretion; Carnitine; Solute carrier (SLC) family transporter; URIC-ACID; LOCI;

D O I：

10.1007/s13577-013-0073-8

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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.

引用

页码：133 / 136

页数：4

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