Role of the urate transporter SLC2A9 gene in susceptibility to gout in New Zealand Maori, Pacific Island, and Caucasian case-control sample sets

Abstract

OBJECTIVE: To examine the role of genetic variation in the renal urate transporter SLC2A9 in gout in New Zealand sample sets of Maori, Pacific Island, and Caucasian ancestry and to determine if the Maori and Pacific Island samples could be useful for fine-mapping. METHODS: Patients (n= 56 Maori, 69 Pacific Island, and 131 Caucasian) were recruited from rheumatology outpatient clinics and satisfied the American College of Rheumatology criteria for gout. The control samples comprised 125 Maori subjects, 41 Pacific Island subjects, and 568 Caucasian subjects without arthritis. SLC2A9 single-nucleotide polymorphisms rs16890979 (V253I), rs5028843, rs11942223, and rs12510549 were genotyped (possible etiologic variants in Caucasians). RESULTS: Association of the major allele of rs16890979, rs11942223, and rs5028843 with gout was observed in all sample sets (P = 3.7 x 10(-7), 1.6 x 10(-6), and 7.6 x 10(-5) for rs11942223 in the Maori, Pacific Island, and Caucasian samples, respectively). One 4-marker haplotype (1/1/2/1; more prevalent in the Maori and Pacific Island control samples) was not observed in a single gout case. CONCLUSION: Our data confirm a role of SLC2A9 in gout susceptibility in a New Zealand Caucasian sample set, with the effect on risk (odds ratio >2.0) greater than previous estimates. We also demonstrate association of SLC2A9 with gout in samples of Maori and Pacific Island ancestry and a consistent pattern of haplotype association. The presence of both alleles of rs16890979 on susceptibility and protective haplotypes in the Maori and Pacific Island sample is evidence against a role for this nonsynonymous variant as the sole etiologic agent. More extensive linkage disequilibrium in Maori and Pacific Island samples suggests that Caucasian samples may be more useful for fine-mapping.