Decreased extra-renal urate excretion is a common cause of hyperuricemia

被引：666

作者：

Ichida, Kimiyoshi ^{[1
,2
]}

Matsuo, Hirotaka ^{[3
]}

Takada, Tappei ^{[4
]}

Nakayama, Akiyoshi ^{[3
,5
]}

Murakami, Keizo ^{[4
]}

Shimizu, Toru ^{[6
]}

Yamanashi, Yoshihide ^{[4
]}

Kasuga, Hiroshi ^{[4
]}

Nakashima, Hiroshi ^{[7
]}

Nakamura, Takahiro ^{[8
,9
]}

Takada, Yuzo ^{[10
]}

Kawamura, Yusuke ^{[3
]}

Inoue, Hiroki ^{[3
]}

Okada, Chisa ^{[3
]}

Utsumi, Yoshitaka ^{[3
]}

Ikebuchi, Yuki ^{[4
]}

Ito, Kousei ^{[4
]}

Nakamura, Makiko ^{[1
]}

Shinohara, Yoshihiko ^{[1
]}

Hosoyamada, Makoto ^{[11
]}

Sakurai, Yutaka ^{[7
]}

Shinomiya, Nariyoshi ^{[3
]}

Hosoya, Tatsuo ^{[2
]}

Suzuki, Hiroshi ^{[4
]}

机构：

[1] Tokyo Univ Pharm & Life Sci, Dept Pathophysiol, Tokyo 1920392, Japan

[2] Jikei Univ, Sch Med, Div Kidney & Hypertens, Dept Internal Med,Minato Ku, Tokyo 1058471, Japan

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

[4] Univ Tokyo, Dept Pharm, Tokyo Univ Hosp, Fac Med,Bunkyo Ku, Tokyo 1138655, Japan

[5] Japan Air Self Def Force, Div 3, Aeromed Lab, Sayama, Saitama 3501324, Japan

[6] Midorigaoka Hosp, Takatsuki, Osaka 5691121, Japan

[7] Natl Def Med Coll, Dept Prevent Med & Publ Hlth, Tokorozawa, Saitama 3598513, Japan

[8] Natl Def Med Coll, Math Lab, Premed Course, Tokorozawa, Saitama 3598513, Japan

[9] Inst Phys & Chem Res RIKEN, Lab Stat Anal, Ctr Genom Med, Minato Ku, Tokyo 1088639, Japan

[10] Natl Def Med Coll, Lab Biofunct, Cent Res Inst, Tokorozawa, Saitama 3598513, Japan

[11] Teikyo Univ, Sch Pharmaceut Sci, Dept Human Physiol & Pathol, Itabashi Ku, Tokyo 1738605, Japan

来源：

NATURE COMMUNICATIONS | 2012年 / 3卷

基金：

日本学术振兴会;

关键词：

CANCER RESISTANCE PROTEIN; URIC-ACID; ANION EXCHANGER; TRANSPORTER; GOUT; IDENTIFICATION; SLC2A9; ABCG2; CLASSIFICATION; ASSOCIATION;

D O I：

10.1038/ncomms1756

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

ABCG2, also known as BCRP, is a high-capacity urate exporter, the dysfunction of which raises gout/hyperuricemia risk. Generally, hyperuricemia has been classified into urate 'overproduction type' and/or 'underexcretion type' based solely on renal urate excretion, without considering an extra-renal pathway. Here we show that decreased extra-renal urate excretion caused by ABCG2 dysfunction is a common mechanism of hyperuricemia. Clinical parameters, including urinary urate excretion, are examined in 644 male outpatients with hyperuricemia. Paradoxically, ABCG2 export dysfunction significantly increases urinary urate excretion and risk ratio of urate overproduction. Abcg2-knockout mice show increased serum uric acid levels and renal urate excretion, and decreased intestinal urate excretion. Together with high ABCG2 expression in extra-renal tissues, our data suggest that the 'overproduction type' in the current concept of hyperuricemia be renamed 'renal overload type', which consists of two subtypes-'extra-renal urate underexcretion' and genuine 'urate overproduction'-providing a new concept valuable for the treatment of hyperuricemia and gout.

引用

页数：7

共 41 条

[1]

[Anonymous], 2010, GUID MAN HYP GOUT, P60

[2]

[Anonymous], 2008, HARRISONS PRINCIPLES

[3]

The multivalent PDZ domain-containing protein PDZK1 regulates transport activity of renal urate-anion exchanger URAT1 via its C terminus [J].

Anzai, N ;

Miyazaki, H ;

Noshiro, R ;

Khamdang, S ;

Chairoungdua, A ;

Shin, HJ ;

Enomoto, A ;

Sakamoto, S ;

Hirata, T ;

Tomita, K ;

Kanai, Y ;

Endou, H .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (44) :45942-45950

[4]

Plasma urate level is directly regulated by a voltage-driven urate efflux transporter URATv1 (SLC2A9) in humans [J].

Anzai, Naohiko ;

Ichida, Kimiyoshi ;

Jutabha, Promsuk ;

Kimura, Toru ;

Babu, Ellappan ;

Jin, Chun Ji ;

Srivastava, Sunena ;

Kitamura, Kenichiro ;

Hisatome, Ichiro ;

Endou, Hitoshi ;

Sakurai, Hiroyuki .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (40) :26834-26838

[5]

Becker M. A., 2001, METABOLIC MOL BASES, P2513

[6]

HYPER-URICEMIA AND GOUT - CLASSIFICATION, COMPLICATIONS AND MANAGEMENT [J].

BOSS, GR ;

SEEGMILLER, JE .

NEW ENGLAND JOURNAL OF MEDICINE, 1979, 300 (26) :1459-1468

[7]

Cheng LSC, 2004, AM J HUM GENET, V75, P498, DOI 10.1086/423429

[8]

Large-scale search of SNPs for type 2 DM susceptibility genes in a Japanese population [J].

Daimon, M ;

Ji, GJ ;

Saitoh, T ;

Oizumi, T ;

Tominaga, M ;

Nakamura, T ;

Ishii, K ;

Matsuura, T ;

Inageda, K ;

Matsumine, H ;

Kido, T ;

Htay, L ;

Kamatani, N ;

Muramatsu, M ;

Kato, T .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2003, 302 (04) :751-758

[9]

Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study [J].

Dehghan, Abbas ;

Kottgen, Anna ;

Yang, Qiong ;

Hwang, Shih Jen ;

Kao, W. H. Linda ;

Rivadeneira, Fernando ;

Boerwinkle, Eric ;

Levy, Daniel ;

Hofman, Albert ;

Astor, Brad C. ;

Benjamin, Emelia J. ;

van Duijn, Cornelia M. ;

Witteman, Jacqueline C. ;

Coresh, Josef ;

Fox, Caroline S. .

LANCET, 2008, 372 (9654) :1953-1961

[10]

SLC2A9 influences uric acid concentrations with pronounced sex-specific effects [J].

Doering, Angela ;

Gieger, Christian ;

Mehta, Divya ;

Gohlke, Henning ;

Prokisch, Holger ;

Coassin, Stefan ;

Fischer, Guido ;

Henke, Kathleen ;

Klopp, Norman ;

Kronenberg, Florian ;

Paulweber, Bernhard ;

Pfeufer, Arne ;

Rosskopf, Dieter ;

Voelzke, Henry ;

Illig, Thomas ;

Meitinger, Thomas ;

Wichmann, H-Erich ;

Meisinger, Christa .

NATURE GENETICS, 2008, 40 (04) :430-436

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