SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout.
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.
Vitart
Veronique
V
MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK.
Rudan
Igor
I
Hayward
Caroline
C
Gray
Nicola K
NK
Floyd
James
J
Palmer
Colin N A
CN
Knott
Sara A
SA
Kolcic
Ivana
I
Polasek
Ozren
O
Graessler
Juergen
J
Wilson
James F
JF
Marinaki
Anthony
A
Riches
Philip L
PL
Shu
Xinhua
X
Janicijevic
Branka
B
Smolej-Narancic
Nina
N
Gorgoni
Barbara
B
Morgan
Joanne
J
Campbell
Susan
S
Biloglav
Zrinka
Z
Barac-Lauc
Lovorka
L
Pericic
Marijana
M
Klaric
Irena Martinovic
IM
Zgaga
Lina
L
Skaric-Juric
Tatjana
T
Wild
Sarah H
SH
Richardson
William A
WA
Hohenstein
Peter
P
Kimber
Charley H
CH
Tenesa
Albert
A
Donnelly
Louise A
LA
Fairbanks
Lynette D
LD
Aringer
Martin
M
McKeigue
Paul M
PM
Ralston
Stuart H
SH
Morris
Andrew D
AD
Rudan
Pavao
P
Hastie
Nicholas D
ND
Campbell
Harry
H
Wright
Alan F
AF
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
D015415:Biomarkers; D051246:Glucose Transport Proteins, Facilitative; D027361:Organic Anion Transporters; C411811:SLC2A9 protein, human; C103862:urate transporter; D014527:Uric Acid; D005632:Fructose