SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout

被引：622

作者：

Vitart, Veronique ^{[1
]}

Rudan, Igor ^{[2
,3
]}

Hayward, Caroline ^{[1
]}

Gray, Nicola K. ^{[1
,12
]}

Floyd, James ^{[4
]}

Palmer, Colin Na ^{[5
]}

Knott, Sara A. ^{[4
]}

Kolcic, Ivana ^{[6
]}

Polasek, Ozren ^{[2
,6
]}

Graessler, Juergen ^{[7
]}

Wilson, James F. ^{[2
]}

Marinaki, Anthony ^{[8
]}

Riches, Philip L. ^{[9
]}

Shu, Xinhua ^{[1
]}

Janicijevic, Branka ^{[11
]}

Smolej-Narancic, Nina ^{[11
]}

Gorgoni, Barbara ^{[12
]}

Morgan, Joanne ^{[1
]}

Campbell, Susan ^{[1
]}

Biloglav, Zrinka ^{[6
]}

Barac-Lauc, Lovorka ^{[11
]}

Pericic, Marijana ^{[11
]}

Klaric, Irena Martinovic ^{[11
]}

Zgaga, Lina ^{[6
]}

Skaric-Juric, Tatjana ^{[11
]}

Wild, Sarah H. ^{[2
]}

Richardson, William A. ^{[1
]}

Hohenstein, Peter ^{[1
]}

Kimber, Charley H. ^{[5
]}

Tenesa, Albert ^{[10
]}

Donnelly, Louise A. ^{[5
]}

Fairbanks, Lynette D. ^{[9
]}

Aringer, Martin ^{[7
]}

McKeigue, Paul M. ^{[2
]}

Ralston, Stuart H. ^{[9
]}

Morris, Andrew D. ^{[13
]}

Rudan, Pavao ^{[11
]}

Hastie, Nicholas D. ^{[1
]}

Campbell, Harry

Wright, Alan F. ^{[1
]}

机构：

[1] Western Gen Hosp, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland

[2] Univ Edinburgh, Sch Med, Community Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland

[3] Univ Split, Fac Med, Croatian Ctr Global Hlth, Split 21000, Croatia

[4] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH9 3JT, Midlothian, Scotland

[5] Ninewells Hosp & Med Sch, Biomed Res Ctr, Populat Pharmacogenet Grp, Dundee DD1 9SY, Scotland

[6] Univ Zagreb, Fac Med, Andriji Stampar Sch Publ Hlth, Zagreb 10000, Croatia

[7] Tech Univ Dresden, Carl Gustav Carus Med Sch, Dept Internal Med, Div Pathol Biochem & Rheumatol, D-01307 Dresden, Germany

[8] Guys & St Thomas Hosp, Univ London Kings Coll, Dept Chem Pathol, Purine Res Lab, London SE1 9RT, England

[9] Univ Edinburgh, Western Gen Hosp, Rheumat Dis Unit, Sch Mol & Clin Med, Edinburgh EH4 2XU, Midlothian, Scotland

[10] Univ Edinburgh, Western Gen Hosp, Colon Canc Genet Grp, Sch Mol & Clin Med, Edinburgh EH4 2XU, Midlothian, Scotland

[11] Inst Anthropol Res, Zagreb 10000, Croatia

[12] Univ Edinburgh, Sch Clin Sci & Community Hlth, Edinburgh EH16 4SB, Midlothian, Scotland

[13] Ninewells Hosp & Med Sch, Div Med Therapeut, Diabet Res Grp, Dundee DD1 9SY, Scotland

来源：

NATURE GENETICS | 2008年 / 40卷 / 04期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

D O I：

10.1038/ng.106

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Uric acid is the end product of purine metabolism in humans and great apes, which have lost hepatic uricase activity, leading to uniquely high serum uric acid concentrations (200 500 mu M) compared with other mammals (3-120 mu M)(1). About 70% of daily urate disposal occurs via the kidneys, and in 5-25% of the human population, impaired renal excretion leads to hyperuricemia(2). About 10% of people with hyperuricemia develop gout, an inflammatory arthritis that results from deposition of monosodium urate crystals in the joint. We have identified genetic variants within a transporter gene, SLC2A9, that explain 1.7-5.3% of the variance in serum uric acid concentrations, following a genome-wide association scan in a Croatian population sample. SLC2A9 variants were also associated with low fractional excretion of uric acid and/or gout in UK, Croatian and German population samples. SLC2A9 is a known fructose transporter(3), and we now show that it has strong uric acid transport activity in Xenopus laevis oocytes.

引用

页码：437 / 442

页数：6

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