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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.

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