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The renal urate transporter SLC17A1 locus: confirmation of association with gout
Authors:Jade E Hollis-Moffatt  Amanda J Phipps-Green  Brett Chapman  Gregory T Jones  Andre van Rij  Peter J Gow  Andrew A Harrison  John Highton  Peter B Jones  Grant W Montgomery  Lisa K Stamp  Nicola Dalbeth  Tony R Merriman
Institution:1. Department of Biochemistry, University of Otago, 710 Cumberland Street, Dunedin, 9054, New Zealand
2. Queensland Institute of Medical Research, 300 Herston Road, 4006, Brisbane, Queensland, Australia
3. Department of Medicine, University of Otago, 210 Great King Street, Dunedin, 9016, New Zealand
4. Department of Rheumatology, Middlemore Hospital, 100 Hospital Road, Auckland, 2025, New Zealand
5. Department of Medicine, University of Otago, 23A Mein Street, Wellington, 6242, New Zealand
6. Department of Medicine, University of Auckland, 2 Park Road, Auckland, 1023, New Zealand
7. Department of Medicine, University of Otago, 2 Riccarton Avenue, Christchurch, 8140, New Zealand
Abstract:

Introduction

Two major gout-causing genes have been identified, the urate transport genes SLC2A9 and ABCG2. Variation within the SLC17A1 locus, which encodes sodium-dependent phosphate transporter 1, a renal transporter of uric acid, has also been associated with serum urate concentration. However, evidence for association with gout is equivocal. We investigated the association of the SLC17A1 locus with gout in New Zealand sample sets.

Methods

Five variants (rs1165196, rs1183201, rs9358890, rs3799344, rs12664474) were genotyped across a New Zealand sample set totaling 971 cases and 1,742 controls. Cases were ascertained according to American Rheumatism Association criteria. Two population groups were studied: Caucasian and Polynesian.

Results

At rs1183201 (SLC17A1), evidence for association with gout was observed in both the Caucasian (odds ratio (OR) = 0.67, P = 3.0 × 10-6) and Polynesian (OR = 0.74, P = 3.0 × 10-3) groups. Meta-analysis confirmed association of rs1183201 with gout at a genome-wide level of significance (OR = 0.70, P = 3.0 × 10-8). Haplotype analysis suggested the presence of a common protective haplotype.

Conclusion

We confirm the SLC17A1 locus as the third associated with gout at a genome-wide level of significance.
Keywords:
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