Study reported in PLoS Medicine says that overexpression of SLC2A9 in embryonic kidney cells doubled urate uptake.

Scientists have found 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. The research team says, however, that variants of this gene do not explain the link between  serum urate levels and high blood pressure.

The investigators used genome-wide association scanning to find that some genetic variants of the human gene SLC2A9 are more common in people with high serum urate levels than in people with normal levels. So the team decided to test whether the protein made by the SLC2A9 gene might be a urate transporter as well as 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, which do not have their own urate transporter. The group found that SLC2A9 transported urate about 50 times faster than it did glucose and that glucose facilitated SLC2A9-mediated urate transport. Similarly, overexpression of SLC2A9 in human embryonic kidney cells more than doubled their urate uptake. Additionally, when the researchers used RNAi to reduce the expression of SLC2A9 in mouse cells that normally makes this protein, urate transport was reduced.

The scientists then looked at two sites for SNPs of SLC2A9 that differed in nearly 900 men who had had their serum urate levels and urinary urate excretion rates measured. They found that certain variations at these two sites were associated with increased serum urate levels and decreased urinary urate excretion. And finally, a study involving 20,000 people found no link between this gene variant and blood pressure.

Researchers from William Harvey Research Institute at Barts and The London School of Medicine and Dentistry, the University of Alberta, and the University of Washington worked on the study. Their findings are published in the October 7 issue of PLoS Medicine.

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