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

Veronique Vitart; Igor Rudan; Caroline Hayward; Nicola K. Gray; James Floyd; Colin N. A. Palmer; Sara A. Knott; Ivana Kolcic; Ozren Polasek; Juergen Graessler; James F. Wilson; Anthony Marinaki; Philip L. Riches; Xinhua Shu; Branka Janicijevic; Nina Smolej-Narancic; Barbara Gorgoni; Joanne Morgan; Susan Campbell; Zrinka Biloglav; Lovorka Barac-Lauc; Marijana Pericic; Irena Martinovic Klaric; Lina Zgaga; Tatjana Skaric-Juric; Sarah H. Wild; William A. Richardson; Peter Hohenstein; Charley H. Kimber; Albert Tenesa; Louise A. Donnelly; Lynette D. Fairbanks; Martin Aringer; Paul M. McKeigue; Stuart H. Ralston; Andrew D. Morris; Pavao Rudan; Nicholas D. Hastie; Harry Campbell; Alan F. Wright

doi:10.1038/ng.106

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

Veronique Vitart, Igor Rudan, Caroline Hayward, Nicola K. Gray, James Floyd, Colin N. A. Palmer, Sara A. Knott, Ivana Kolcic, Ozren Polasek, Juergen Graessler, James F. Wilson, Anthony Marinaki, Philip L. Riches, Xinhua Shu, Branka Janicijevic, Nina Smolej-Narancic, Barbara Gorgoni, Joanne Morgan, Susan Campbell, Zrinka BiloglavLovorka Barac-Lauc, Marijana Pericic, Irena Martinovic Klaric, Lina Zgaga, Tatjana Skaric-Juric, Sarah H. Wild, William A. Richardson, Peter Hohenstein, Charley H. Kimber, Albert Tenesa, Louise A. Donnelly, Lynette D. Fairbanks, Martin Aringer, Paul M. McKeigue, Stuart H. Ralston, Andrew D. Morris, Pavao Rudan, Nicholas D. Hastie, Harry Campbell, Alan F. Wright (Lead / Corresponding author)

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Abstract

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.

Original language	English
Pages (from-to)	437-442
Number of pages	6
Journal	Nature Genetics
Volume	40
Issue number	4
DOIs	https://doi.org/10.1038/ng.106
Publication status	Published - Apr 2008

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Vitart, V., Rudan, I., Hayward, C., Gray, N. K., Floyd, J., Palmer, C. N. A., Knott, S. A., Kolcic, I., Polasek, O., Graessler, J., Wilson, J. F., Marinaki, A., Riches, P. L., Shu, X., Janicijevic, B., Smolej-Narancic, N., Gorgoni, B., Morgan, J., Campbell, S., ... Wright, A. F. (2008). SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. Nature Genetics, 40(4), 437-442. https://doi.org/10.1038/ng.106

@article{c3234617835f4633bb71c622442926da,

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

abstract = "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.",

author = "Veronique Vitart and Igor Rudan and Caroline Hayward and Gray, {Nicola K.} and James Floyd and Palmer, {Colin N. A.} and Knott, {Sara A.} and Ivana Kolcic and Ozren Polasek and Juergen Graessler and Wilson, {James F.} and Anthony Marinaki and Riches, {Philip L.} and Xinhua Shu and Branka Janicijevic and Nina Smolej-Narancic and Barbara Gorgoni and Joanne Morgan and Susan Campbell and Zrinka Biloglav and Lovorka Barac-Lauc and Marijana Pericic and Klaric, {Irena Martinovic} and Lina Zgaga and Tatjana Skaric-Juric and Wild, {Sarah H.} and Richardson, {William A.} and Peter Hohenstein and Kimber, {Charley H.} and Albert Tenesa and Donnelly, {Louise A.} and Fairbanks, {Lynette D.} and Martin Aringer and McKeigue, {Paul M.} and Ralston, {Stuart H.} and Morris, {Andrew D.} and Pavao Rudan and Hastie, {Nicholas D.} and Harry Campbell and Wright, {Alan F.}",

year = "2008",

month = apr,

doi = "10.1038/ng.106",

language = "English",

volume = "40",

pages = "437--442",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

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Vitart, V, Rudan, I, Hayward, C, Gray, NK, Floyd, J, Palmer, CNA, Knott, SA, Kolcic, I, Polasek, O, Graessler, J, Wilson, JF, Marinaki, A, Riches, PL, Shu, X, Janicijevic, B, Smolej-Narancic, N, Gorgoni, B, Morgan, J, Campbell, S, Biloglav, Z, Barac-Lauc, L, Pericic, M, Klaric, IM, Zgaga, L, Skaric-Juric, T, Wild, SH, Richardson, WA, Hohenstein, P, Kimber, CH, Tenesa, A, Donnelly, LA, Fairbanks, LD, Aringer, M, McKeigue, PM, Ralston, SH, Morris, AD, Rudan, P, Hastie, ND, Campbell, H & Wright, AF 2008, 'SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout', Nature Genetics, vol. 40, no. 4, pp. 437-442. https://doi.org/10.1038/ng.106

TY - JOUR

T1 - SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout

AU - Vitart, Veronique

AU - Rudan, Igor

AU - Hayward, Caroline

AU - Gray, Nicola K.

AU - Floyd, James

AU - Palmer, Colin N. A.

AU - Knott, Sara A.

AU - Kolcic, Ivana

AU - Polasek, Ozren

AU - Graessler, Juergen

AU - Wilson, James F.

AU - Marinaki, Anthony

AU - Riches, Philip L.

AU - Shu, Xinhua

AU - Janicijevic, Branka

AU - Smolej-Narancic, Nina

AU - Gorgoni, Barbara

AU - Morgan, Joanne

AU - Campbell, Susan

AU - Biloglav, Zrinka

AU - Barac-Lauc, Lovorka

AU - Pericic, Marijana

AU - Klaric, Irena Martinovic

AU - Zgaga, Lina

AU - Skaric-Juric, Tatjana

AU - Wild, Sarah H.

AU - Richardson, William A.

AU - Hohenstein, Peter

AU - Kimber, Charley H.

AU - Tenesa, Albert

AU - Donnelly, Louise A.

AU - Fairbanks, Lynette D.

AU - Aringer, Martin

AU - McKeigue, Paul M.

AU - Ralston, Stuart H.

AU - Morris, Andrew D.

AU - Rudan, Pavao

AU - Hastie, Nicholas D.

AU - Campbell, Harry

AU - Wright, Alan F.

PY - 2008/4

Y1 - 2008/4

N2 - 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.

AB - 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.

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U2 - 10.1038/ng.106

DO - 10.1038/ng.106

M3 - Article

SN - 1061-4036

VL - 40

SP - 437

EP - 442

JO - Nature Genetics

JF - Nature Genetics

IS - 4

ER -

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

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