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

Arthritis Rheum. 2009 Nov;60(11):3485-92. doi: 10.1002/art.24938.

Abstract

Objective: To examine the role of genetic variation in the renal urate transporter SLC2A9 in gout in New Zealand sample sets of Māori, Pacific Island, and Caucasian ancestry and to determine if the Māori and Pacific Island samples could be useful for fine-mapping.

Methods: Patients (n= 56 Māori, 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 Māori 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 Māori, Pacific Island, and Caucasian samples, respectively). One 4-marker haplotype (1/1/2/1; more prevalent in the Māori 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 Māori 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 Māori and Pacific Island sample is evidence against a role for this nonsynonymous variant as the sole etiologic agent. More extensive linkage disequilibrium in Māori and Pacific Island samples suggests that Caucasian samples may be more useful for fine-mapping.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Case-Control Studies
  • Ethnic Groups / ethnology
  • Ethnic Groups / genetics
  • European Continental Ancestry Group / ethnology
  • European Continental Ancestry Group / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Glucose Transport Proteins, Facilitative / genetics*
  • Gout / ethnology
  • Gout / genetics*
  • Haplotypes / genetics
  • Humans
  • Linkage Disequilibrium / genetics
  • Male
  • Middle Aged
  • New Zealand
  • Oceanic Ancestry Group / ethnology
  • Oceanic Ancestry Group / genetics*
  • Organic Anion Transporters / genetics*
  • Pacific Islands
  • Polymorphism, Single Nucleotide / genetics*
  • Young Adult

Substances

  • Glucose Transport Proteins, Facilitative
  • Organic Anion Transporters
  • SLC2A9 protein, human
  • urate transporter