title: Role of the urate transporter SLC2A9 gene in susceptibility to gout in New Zealand Māori, 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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Jade E
authors.initials: JE
authors.lastname: Hollis-Moffatt
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.forename: Nicola
authors.initials: N
authors.lastname: Dalbeth
authors.forename: Marilyn E
authors.initials: ME
authors.lastname: Merriman
authors.forename: Ruth
authors.initials: R
authors.lastname: Topless
authors.forename: Chloe
authors.initials: C
authors.lastname: Waddell
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Gow
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Harrison
authors.forename: John
authors.initials: J
authors.lastname: Highton
authors.forename: Peter B B
authors.initials: PB
authors.lastname: Jones
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Stamp
authors.forename: Tony R
authors.initials: TR
authors.lastname: Merriman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D005006:Ethnicity / Q000208:ethnology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D006073:Gout / Q000208:ethnology / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009520:New Zealand; D027361:Organic Anion Transporters / Q000235:genetics*; D010139:Pacific Islands; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People / Q000208:ethnology / Q000235:genetics*; D055815:Young Adult
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D027361:Organic Anion Transporters; C411811:SLC2A9 protein, human; C103862:urate transporter