title: Twenty-eight loci that influence serum urate levels: analysis of association with gout.
abstract: OBJECTIVE
  Twenty-eight genetic loci are associated with serum urate levels in Europeans. Evidence for association with gout at most loci is absent, equivocal or not replicated. Our aim was to test the loci for association with gout meeting the American College of Rheumatology gout classification criteria in New Zealand European and Polynesian case-control sample sets.
  
  
  METHODS
  648 European cases and 1550 controls, and 888 Polynesian (Ma¯ori and Pacific) cases and 1095 controls were genotyped. Association with gout was tested by logistic regression adjusting for age and sex. Power was adequate (>0.7) to detect effects of OR>1.3.
  
  
  RESULTS
  We focused on 24 loci without previous consistent evidence for association with gout. In Europeans, we detected association at seven loci, one of which was the first report of association with gout (IGF1R). In Polynesian, association was detected at three loci. Meta-analysis revealed association at eight loci-two had not previously been associated with gout (PDZK1 and MAF). In participants with higher Polynesian ancestry, there was association in an opposing direction to Europeans at PRKAG2 and HLF (HLF is the first report of association with gout). There was obvious inconsistency of gout association at four loci (GCKR, INHBC, SLC22A11, SLC16A9) that display very similar effects on urate levels.
  
  
  CONCLUSIONS
  We provide the first evidence for association with gout at four loci (IGF1R, PDZK1, MAF, HLF). Understanding why there is lack of correlation between urate and gout effect sizes will be important in understanding the aetiology of gout.
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: A J
authors.initials: AJ
authors.lastname: Phipps-Green
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: M E
authors.initials: ME
authors.lastname: Merriman
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: R
authors.initials: R
authors.lastname: Topless
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: S
authors.initials: S
authors.lastname: Altaf
authors.affiliation: Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
authors.forename: G W
authors.initials: GW
authors.lastname: Montgomery
authors.affiliation: Department of Medicine, University of Auckland, Auckland, New Zealand.
authors.forename: C
authors.initials: C
authors.lastname: Franklin
authors.affiliation: Department of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: G T
authors.initials: GT
authors.lastname: Jones
authors.affiliation: Department of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: A M
authors.initials: AM
authors.lastname: van Rij
authors.affiliation: Waikato District Health Board, Hamilton, New Zealand.
authors.forename: D
authors.initials: D
authors.lastname: White
authors.affiliation: Department of Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: L K
authors.initials: LK
authors.lastname: Stamp
authors.affiliation: Department of Medicine, University of Auckland, Auckland, New Zealand.
authors.forename: N
authors.initials: N
authors.lastname: Dalbeth
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: T R
authors.initials: TR
authors.lastname: Merriman
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D005838:Genotype; D006073:Gout / Q000097:blood* / Q000235:genetics*; D006801:Humans; D028322:Inhibin-beta Subunits / Q000235:genetics; D008565:Membrane Proteins; D027501:Monocarboxylic Acid Transporters / Q000235:genetics; D009520:New Zealand; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics; D051257:Proto-Oncogene Proteins c-maf / Q000235:genetics; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000235:genetics; D014527:Uric Acid / Q000097:blood*; D044465:White People / Q000235:genetics*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D002352:Carrier Proteins; C490671:HLF protein, human; C000597236:IGF1R protein, human; C504186:INHBC protein, human; C495607:MAF protein, human; D008565:Membrane Proteins; D027501:Monocarboxylic Acid Transporters; D029362:Organic Anion Transporters, Sodium-Independent; C484659:PDZK1 protein, human; D051257:Proto-Oncogene Proteins c-maf; D017451:Receptors, Somatomedin; C549233:SLC16A9 protein, human; C427207:SLC22A11 protein, human; D014527:Uric Acid; D028322:Inhibin-beta Subunits; D017526:Receptor, IGF Type 1; C526223:PRKAG2 protein, human; D055372:AMP-Activated Protein Kinases
keywords: Epidemiology; Gene Polymorphism; Gout