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 microM) compared with other mammals (3-120 microM). About 70% of daily urate disposal occurs via the kidneys, and in 5-25% of the human population, impaired renal excretion leads to hyperuricemia. 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, and we now show that it has strong uric acid transport activity in Xenopus laevis oocytes.
authors.affiliation: MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK.
authors.forename: Veronique
authors.initials: V
authors.lastname: Vitart
authors.forename: Igor
authors.initials: I
authors.lastname: Rudan
authors.forename: Caroline
authors.initials: C
authors.lastname: Hayward
authors.forename: Nicola K
authors.initials: NK
authors.lastname: Gray
authors.forename: James
authors.initials: J
authors.lastname: Floyd
authors.forename: Colin N A
authors.initials: CN
authors.lastname: Palmer
authors.forename: Sara A
authors.initials: SA
authors.lastname: Knott
authors.forename: Ivana
authors.initials: I
authors.lastname: Kolcic
authors.forename: Ozren
authors.initials: O
authors.lastname: Polasek
authors.forename: Juergen
authors.initials: J
authors.lastname: Graessler
authors.forename: James F
authors.initials: JF
authors.lastname: Wilson
authors.forename: Anthony
authors.initials: A
authors.lastname: Marinaki
authors.forename: Philip L
authors.initials: PL
authors.lastname: Riches
authors.forename: Xinhua
authors.initials: X
authors.lastname: Shu
authors.forename: Branka
authors.initials: B
authors.lastname: Janicijevic
authors.forename: Nina
authors.initials: N
authors.lastname: Smolej-Narancic
authors.forename: Barbara
authors.initials: B
authors.lastname: Gorgoni
authors.forename: Joanne
authors.initials: J
authors.lastname: Morgan
authors.forename: Susan
authors.initials: S
authors.lastname: Campbell
authors.forename: Zrinka
authors.initials: Z
authors.lastname: Biloglav
authors.forename: Lovorka
authors.initials: L
authors.lastname: Barac-Lauc
authors.forename: Marijana
authors.initials: M
authors.lastname: Pericic
authors.forename: Irena Martinovic
authors.initials: IM
authors.lastname: Klaric
authors.forename: Lina
authors.initials: L
authors.lastname: Zgaga
authors.forename: Tatjana
authors.initials: T
authors.lastname: Skaric-Juric
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Wild
authors.forename: William A
authors.initials: WA
authors.lastname: Richardson
authors.forename: Peter
authors.initials: P
authors.lastname: Hohenstein
authors.forename: Charley H
authors.initials: CH
authors.lastname: Kimber
authors.forename: Albert
authors.initials: A
authors.lastname: Tenesa
authors.forename: Louise A
authors.initials: LA
authors.lastname: Donnelly
authors.forename: Lynette D
authors.initials: LD
authors.lastname: Fairbanks
authors.forename: Martin
authors.initials: M
authors.lastname: Aringer
authors.forename: Paul M
authors.initials: PM
authors.lastname: McKeigue
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Ralston
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Morris
authors.forename: Pavao
authors.initials: P
authors.lastname: Rudan
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Hastie
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.forename: Alan F
authors.initials: AF
authors.lastname: Wright
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001693:Biological Transport, Active; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016022:Case-Control Studies; D017523:Croatia; D005260:Female; D005632:Fructose / Q000378:metabolism; D008040:Genetic Linkage; D015894:Genome, Human; D005838:Genotype; D005858:Germany; D051246:Glucose Transport Proteins, Facilitative / Q000502:physiology*; D006073:Gout / Q000097:blood* / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D027361:Organic Anion Transporters / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014527:Uric Acid / Q000097:blood*; D014982:Xenopus laevis / Q000378:metabolism
chemical_list: D015415:Biomarkers; D051246:Glucose Transport Proteins, Facilitative; D027361:Organic Anion Transporters; C411811:SLC2A9 protein, human; C103862:urate transporter; D014527:Uric Acid; D005632:Fructose