journal.pmed.0050197.pdf (483.58 kB)
SLC2A9 is a high-capacity urate transporter in humans.
journal contribution
posted on 2012-10-24, 09:04 authored by M. J. Caulfield, P. B. Munroe, D. O'Neill, K. Witkowska, F. J. Charchar, M. Doblado, S. Evans, S. Eyheramendy, A. Onipinla, P. Howard, S. Shaw-Hawkins, R. J. Dobson, C. Wallace, S. J. Newhouse, M. Brown, J. M. Connell, A. Dominiczak, M. Farrall, G. M. Lathrop, Nilesh J. Samani, M. Kumari, M. Marmot, E. Brunner, J. Chambers, P. Elliott, J. Kooner, M. Laan, E. Org, G. Veldre, M. Viigimaa, F. P. Cappuccio, C. Ji, R. Iacone, P. Strazzullo, K. H. Moley, C. CheesemanSerum uric acid levels in humans are influenced by diet, cellular breakdown, and renal elimination, and correlate with blood pressure, metabolic syndrome, diabetes, gout, and cardiovascular disease. Recent genome-wide association scans have found common genetic variants of SLC2A9 to be associated with increased serum urate level and gout. The SLC2A9 gene encodes a facilitative glucose transporter, and it has two splice variants that are highly expressed in the proximal nephron, a key site for urate handling in the kidney. We investigated whether SLC2A9 is a functional urate transporter that contributes to the longstanding association between urate and blood pressure in man.
Funding
The BRIGHT study and current work are supported by the Medical Research Council (MRC) of Great Britain (grant no. G9521010D) and the British Heart Foundation (grant no. PG02/128). K.H. Moley is supported by an American Diabetes Association Research Grant. S. Evans is funded by National Institutes of Health (NIH) grant no. NIH-NIDDK T32-DK07120. C. Cheeseman is funded by the Canadian Breast Cancer Foundation. The Wellcome Trust Case Control Consortium was funded by the Wellcome Trust (grant number 076113/B/04/Z). The Barts and The London Charity funded the Barts and The London Genome Centre. A. Dominiczak and N.J. Samani are British Heart Foundation Chair holders. C. Wallace is funded by the British Heart Foundation (grant no. FS/05/061/19501). The LOLIPOP Study was funded by the British Heart Foundation. The HYPEST sample collection was financed by Wellcome Trust International Senior Research Fellowship to M. Laan (grant no. 070191/Z/03/Z) in Biomedical Science in Central Europe and by Estonian Ministry of Education and Science core grant no. 0182721s06. M. Marmot is supported by an MRC Research Professorship. The Whitehall II study has been supported by grants from the UK: MRC; Economic and Social Research Council; British Heart Foundation; Health and Safety Executive; Department of Health; National Heart Lung and Blood Institute (grant no. HL36310); and from the US: NIH, National Institute on Aging (NIA; grant no. AG13196); NIH, Agency for Health Care Policy Research (grant no. HS06516); and the John D. and Catherine T. MacArthur Foundation Research Networks on Successful Midlife Development and Socio-economic Status and Health. Samples from the English Longitudinal Study of Ageing (ELSA) DNA Repository (EDNAR), received support under a grant (AG1764406S1) awarded by the NIA. ELSA was developed by a team of researchers based at the National Centre for Social Research, University College London and the Institute of Fiscal Studies. The data were collected by the Nat
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PLoS Medicine, 2008, 5 (10), pp. e197-e197Published in
PLoS Medicineissn
1549-1277eissn
1549-1676Copyright date
2008Available date
2012-10-24Publisher DOI
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http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0050197Language
engAdministrator link
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AdultAgedAnimalsBiological TransportBlottingWesternCell LineTumorChromatographyThin LayerFatty AcidsVolatileFemaleFructoseGlucoseGlucose Transport ProteinsFacilitativeHexosesHumansImmunohistochemistryKineticsLongitudinal StudiesMiceMiddle AgedOocytesOrganic Anion TransportersUric AcidUricosuric AgentsXenopus laevis
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