Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers discover that SLC2A9 is a high-capacity urate transporter in humans

07.10.2008
An international team of researchers led by Professors Mark Caulfield and Patricia Munroe, from the William Harvey Research Institute at Barts and The London School of Medicine and Dentistry with Chris Cheeseman at the University of Alberta in Canada and Kelle Moley at the University of Washington in USA, have shown that the SLC2A9 gene, which encodes a glucose transporter, is also a high-capacity urate transporter, and thus possibly a new drug target for gout. Their findings are published in this week's PLoS Medicine (7 October 2008).

Several urate transporters have already been identified but recently, using an approach called genome-wide association scanning, Caulfield and others found that some genetic variants of a human gene called SLC2A9 are more common in people with high serum urate levels than in people with normal levels. SLC2A9 encodes a glucose transporter (a protein that helps to move the sugar glucose through cell membranes) and is highly expressed in the kidney's main urate handling site. Professor Caulfield and his team investigated the possibility that the protein made by the SLC2A9 gene might be a urate transporter and tested whether genetic variations in SLC2A9 might be responsible for the association between serum urate levels and high blood pressure.

The team first expressed SLC2A9 in frog eggs, a type of cell that does not have its own urate transporter. They found that SLC2A9 transported urate about 50 times faster than glucose, and that glucose facilitated SLC2A9-mediated urate transport. Similarly, over expression of SLC2A9 in human embryonic kidney cells more than doubled their urate uptake. Conversely, when the researchers used a technique called RNA interference to reduce the expression of mouse SLC2A9 in mouse cells that normally makes this protein, urate transport was reduced. Researchers then looked at two genetic variations within SLC2A9 that vary between individuals (so-called single polynucleotide polymorphisms) in nearly 900 men who had had their serum urate levels and urinary urate excretion rates measured. They found that certain genetic variations at these two sites were associated with increased serum urate levels and decreased urinary urate excretion. Finally, the researchers used a statistical technique called meta-analysis to look for an association between one of the SLC2A9 gene variants and blood pressure. In two separate meta-analyses that together involved more than 20,000 participants in several studies, there was no association between this gene variant and blood pressure.

Overall, these findings indicate that SLCA9 is a high capacity urate transporter, and suggest that this protein plays an important part in controlling serum urate levels. They provide confirmation that common genetic variants in SLC2A9 affect serum urate levels to a marked degree, although they do not show exactly which genetic variant is responsible for increasing serum urate levels. They also provide important new insights into how the kidneys normally handle urate and suggest ways in which this essential process may sometimes go wrong. The findings could eventually lead to new treatments for gout and possibly for other diseases that are associated with increased serum urate levels.

Professor Mark Caulfield said: "This MRC funded study shows how a team of international researchers can find a completely unsuspected mechanism for urate handling in the kidney. Such discoveries could pave the way for new medicines."

Citation: Caulfield MJ, Munroe PB, O'Neill D, Witkowska K, Charchar FJ, et al. (2008) SLC2A9 is a high-capacity urate transporter in humans. PLoS Med 5(9): e197. doi:10.1371/journal.pmed.0050197

For further information contact:
Alex Fernandes
Communications Office
Queen Mary, University of London
Tel: 020 7882 7910
email: a.fernandes@qmul.ac.uk
Barts and The London School of Medicine and Dentistry
Barts and The London School of Medicine and Dentistry – at Queen Mary, University of London - offers international levels of excellence in research and teaching while serving a population of unrivalled diversity amongst which cases of diabetes, hypertension, heart disease, TB, oral disease and cancers are prevalent, within east London and the wider Thames Gateway. Through partnership with our linked trusts, notably Barts and The London NHS Trust, and our associated University Hospital trusts – Homerton, Newham, Whipps Cross and Queen's – the School's research and teaching is informed by an exceptionally wide ranging and stimulating clinical environment.

At the heart of the School's mission lies world class research, the result of a focused programme of recruitment of leading research groups from the UK and abroad and a £100 million investment in state-of-the-art facilities. Research is focused on translational research, cancer, cardiology, clinical pharmacology, inflammation, infectious diseases, stem cells, dermatology, gastroenterology, haematology, diabetes, neuroscience, surgery and dentistry.

The School is nationally and internationally recognised for research in these areas, reflected in the £40 million it attracts annually in research income. Its fundamental mission, with its partner NHS Trusts, and other partner organisations such as CRUK, is to ensure that that the best possible clinical service is underpinned by the very latest developments in scientific and clinical teaching, training and research.

Alex Fernandes | EurekAlert!
Further information:
http://www.qmul.ac.uk

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>