title: SLC2A9 Genotype Is Associated with SLC2A9 Gene Expression and Urinary Uric Acid Concentration.
abstract: OBJECTIVE
  SLC2A9 gene variants have been associated with urinary uric acid (UA) concentration, but little is known about the functional mechanism linking these gene variants with UA. SLC2A9 encodes a UA transporter present in the proximal tubule of the kidney, and gene expression levels of SLC2A9 and other genes in the uricosuric pathway (ABCG2, SLC17A1, SLC17A3, and SLC22A12) could potentially mediate the relationship between SLC2A9 gene variants and urinary UA excretion.
  
  
  METHODS
  The association between urinary UA concentrations and single nucleotide polymorphisms (SNPs) within the SLC2A9 gene region, expression levels of genes in the uricosuric pathway, and dietary protein intake were analyzed for a sample of non-Hispanic white participants from the Genetic Epidemiology Network of Arteriopathy (GENOA) cohort. The SLC2A9 SNP most significantly associated with urinary UA concentration was then tested for associations with gene expression levels from uric acid absorption/secretion associated genes. Models including interactions between dietary protein (total, animal, and vegetable) and genetic factors were also assessed.
  
  
  RESULTS
  The most significant SLC2A9 SNP associated with urinary UA (rs12509955, corrected p = 0.001) was also associated with SLC2A9 gene expression levels (corrected p = 0.0084); however, SLC2A9 gene expression levels were not significantly associated with urinary UA concentrations (p = 0.509). The interactions between rs12509955 and total dietary protein, and SLC2A9 gene-level gene expression and dietary vegetable protein on the outcome of urinary UA were marginally significant (p = 0.11 and p = 0.07, respectively). Gene expression level of one SLC2A9 transcript had a significant interaction with dietary animal protein (SLC2A9-001 ENST00000506583, p = 0.01) and a marginally significant interaction with total dietary protein (p = 0.07) on urinary UA.
  
  
  CONCLUSIONS
  Our results illustrate that SNPs in the SLC2A9 gene influence SLC2A9 gene expression as well as urinary UA excretion. Evidence is also suggestive that gene-by-diet interactions may disproportionately increase urinary UA in genetically susceptible individuals that consume higher amounts of protein.
authors.affiliation: Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, United States of America; Institute for Social Research, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Erin B
authors.initials: EB
authors.lastname: Ware
authors.affiliation: Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Ellen
authors.initials: E
authors.lastname: Riehle
authors.affiliation: Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Smith
authors.affiliation: Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United States of America.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Turner
authors.affiliation: Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Sharon L R
authors.initials: SL
authors.lastname: Kardia
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, United States of America; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States of America.
authors.forename: John C
authors.initials: JC
authors.lastname: Lieske
mesh_terms: D000368:Aged; D004044:Dietary Proteins / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005838:Genotype; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014527:Uric Acid / Q000652:urine*
chemical_list: D004044:Dietary Proteins; D051246:Glucose Transport Proteins, Facilitative; C411811:SLC2A9 protein, human; D014527:Uric Acid