Open Access Research article

The SLC2A9 nonsynonymous Arg265His variant and gout: evidence for a population-specific effect on severity

Jade E Hollis-Moffatt1, Peter J Gow2, Andrew A Harrison3, John Highton4, Peter BB Jones5, Lisa K Stamp6, Nicola Dalbeth5 and Tony R Merriman1*

Author Affiliations

1 Department of Biochemistry, University of Otago, 710 Cumberland Street, Dunedin 9012, New Zealand

2 Department of Rheumatology, Middlemore Hospital, 100 Hospital Road, Auckland 2025, New Zealand

3 Department of Medicine, University of Otago, 23A Mein Street, Wellington 6242, New Zealand

4 Department of Medicine, University of Otago, 201 Great King Street, Dunedin 9016, New Zealand

5 Department of Medicine, University of Auckland, 2 Park Road, Auckland 1023, New Zealand

6 Department of Medicine, University of Otago, 2 Riccarton Avenue, Christchurch 8140, New Zealand

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Arthritis Research & Therapy 2011, 13:R85  doi:10.1186/ar3356

Published: 9 June 2011

Abstract

Introduction

The C allele of the nonsynonymous Arg265His (rs3733591) variant of SLC2A9 confers risk for gout in Han Chinese, Solomon Island and Japanese samples, with a stronger role in tophaceous gout. There is no evidence for an association with gout in Caucasian populations. In the present study, we tested rs3733591 for association with gout in New Zealand (NZ) Māori, Pacific Island and Caucasian samples.

Methods

Rs3733591 was genotyped across gout patients (n = 229, 232 and 327 NZ Māori, Pacific Island and Caucasian samples, respectively) and non-gout controls (n = 343, 174 and 638 Māori, Pacific Island and Caucasian samples, respectively). Further Caucasian sample sets consisting of 67 cases and 4,712 controls as well as 153 cases and 6,969 controls were obtained from the Framingham Heart Study and the Atherosclerosis Risk in Communities study, respectively. The Polynesian samples were analyzed according to Eastern and Western Polynesian ancestry.

Results

No evidence for risk conferred by the C allele of rs3733591 with gout was found in the sample sets of NZ Māori (odd ratio (OR) = 0.98, P = 0.86), Eastern Polynesians (OR = 0.99, P = 0.92), Western Polynesians (OR = 1.16, P = 0.36) or combined Caucasians (OR = 1.15, P = 0.13). The C allele was significantly overrepresented in Māori tophaceous cases compared to cases without tophi (OR = 2.21, P = 0.008), but not in the other ancestral groupings.

Conclusions

Noting that our study's power was limited for detecting weak genetic effects, we were unable to replicate associations of rs3733591 with gout in Eastern Polynesian, Western Polynesian and Caucasian samples. However, consistent with a previous study of Han Chinese and Solomon Island populations, our data suggest that rs3733591 could be a marker of severe gout in some populations. Our results also suggest that the effect of this variant is population-specific, further confirming population heterogeneity regarding the association of SLC2A9 with gout.