title: Sugar-sweetened beverage consumption: a risk factor for prevalent gout with SLC2A9 genotype-specific effects on serum urate and risk of gout.
abstract: OBJECTIVE
  Consumption of high fructose corn syrup (HFCS)-sweetened beverages increases serum urate and risk of incident gout. Genetic variants in SLC2A9, that exchanges uric acid for glucose and fructose, associate with gout. We tested association between sugar (sucrose)-sweetened beverage (SSB) consumption and prevalent gout. We also tested the hypothesis that SLC2A9 genotype and SSB consumption interact to determine gout risk.
  
  
  METHODS
  Participants were 1634 New Zealand (NZ) European Caucasian, Ma¯ori and Pacific Island people and 7075 European Caucasians from the Atherosclerosis Risk in Communities (ARIC) study. NZ samples were genotyped for rs11942223 and ARIC for rs6449173. Effect estimates were multivariate adjusted.
  
  
  RESULTS
  SSB consumption increased gout risk. The OR for four drinks/day relative to zero was 6.89 (p=0.045), 5.19 (p=0.010) and 2.84 (p=0.043) for European Caucasian, Ma¯ori and Pacific Islanders, respectively. With each extra daily SSB serving, carriage of the gout-protective allele of SLC2A9 associated with a 15% increase in risk (p=0.078), compared with a 12% increase in non-carriers (p=0.002). The interaction term was significant in pooled (pInteraction=0.01) but not meta-analysed (pInteraction=0.99) data. In ARIC, with each extra daily serving, a greater increase in serum urate protective allele carriers (0.005 (p=8.7×10(-5)) compared with 0.002 (p=0.016) mmol/L) supported the gout data (pInteraction=0.062).
  
  
  CONCLUSIONS
  Association of SSB consumption with prevalent gout supports reduction of SSB in management. The interaction data suggest that SLC2A9-mediated renal uric acid excretion is physiologically influenced by intake of simple sugars derived from SSB, with SSB exposure negating the gout risk discrimination of SLC2A9.
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Batt
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Phipps-Green
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Black
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Murray
authors.initials: M
authors.lastname: Cadzow
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Marilyn E
authors.initials: ME
authors.lastname: Merriman
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Ruth
authors.initials: R
authors.lastname: Topless
authors.affiliation: Department of Rheumatology, Middlemore Hospital, Auckland, New Zealand.
authors.forename: Peter
authors.initials: P
authors.lastname: Gow
authors.affiliation: Department of Medicine, University of Otago, Wellington, New Zealand.
authors.forename: Andrew
authors.initials: A
authors.lastname: Harrison
authors.affiliation: Department of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: John
authors.initials: J
authors.lastname: Highton
authors.affiliation: Department of Medicine, University of Auckland, Auckland, New Zealand.
authors.forename: Peter
authors.initials: P
authors.lastname: Jones
authors.affiliation: Department of Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: Lisa
authors.initials: L
authors.lastname: Stamp
authors.affiliation: Department of Medicine, University of Auckland, Auckland, New Zealand.
authors.forename: Nicola
authors.initials: N
authors.lastname: Dalbeth
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Tony R
authors.initials: TR
authors.lastname: Merriman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001628:Beverages; D016022:Case-Control Studies; D019422:Dietary Sucrose / Q000009:adverse effects*; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D006073:Gout / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D033461:Hyperuricemia / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D014527:Uric Acid / Q000097:blood*; D055815:Young Adult
chemical_list: D019422:Dietary Sucrose; D051246:Glucose Transport Proteins, Facilitative; C411811:SLC2A9 protein, human; D014527:Uric Acid
keywords: Epidemiology; Gene Polymorphism; Gout
references.citation: Ann Rheum Dis. 2013 Nov;72(11):1868-73
references.pmid: 23349133
references.citation: Nephron. 1975;14(1):7-20
references.pmid: 1124137
references.citation: PLoS Med. 2008 Oct 7;5(10):e197
references.pmid: 18842065
references.citation: Metabolism. 2012 May;61(5):641-51
references.pmid: 22152650
references.citation: Arthritis Rheum. 2008 Jan 15;59(1):109-16
references.pmid: 18163396
references.citation: Semin Nephrol. 2011 Sep;31(5):420-5
references.pmid: 22000648
references.citation: Arthritis Rheum. 2007 Jun;56(6):2049-55
references.pmid: 17530645
references.citation: J Biol Chem. 2004 Apr 16;279(16):16229-36
references.pmid: 14739288
references.citation: Nat Genet. 2008 Apr;40(4):430-6
references.pmid: 18327256
references.citation: Am J Physiol Renal Physiol. 2012 Aug 15;303(4):F527-39
references.pmid: 22647630
references.citation: Arch Intern Med. 2009 Mar 9;169(5):502-7
references.pmid: 19273781
references.citation: Lancet. 1967 Sep 9;2(7515):528-31
references.pmid: 4166890
references.citation: Am J Physiol Renal Physiol. 2009 Sep;297(3):F612-9
references.pmid: 19587147
references.citation: Nat Genet. 2013 Feb;45(2):145-54
references.pmid: 23263486
references.citation: Semin Nephrol. 2011 Sep;31(5):426-32
references.pmid: 22000649
references.citation: Arthritis Rheum. 1977 Apr;20(3):895-900
references.pmid: 856219
references.citation: N Engl J Med. 2004 Mar 11;350(11):1093-103
references.pmid: 15014182
references.citation: Am J Med. 1987 Mar;82(3):421-6
references.pmid: 3826098
references.citation: Joint Bone Spine. 2011 Jan;78(1):35-40
references.pmid: 20472486
references.citation: Arthritis Care Res (Hoboken). 2012 Mar;64(3):389-96
references.pmid: 22076806
references.citation: Lancet. 2004 Apr 17;363(9417):1277-81
references.pmid: 15094272
references.citation: BMJ. 2008 Feb 9;336(7639):309-12
references.pmid: 18244959
references.citation: J Nutr. 2012 May;142(5):916-23
references.pmid: 22457397
references.citation: Arthritis Rheum. 2009 Nov;60(11):3485-92
references.pmid: 19877038
references.citation: Endocr Rev. 2009 Feb;30(1):96-116
references.pmid: 19151107
references.citation: JAMA. 2010 Nov 24;304(20):2270-8
references.pmid: 21068145