title: Tubular urate transporter gene polymorphisms differentiate patients with gout who have normal and decreased urinary uric acid excretion.
abstract: OBJECTIVE
  Primary gout has been associated with single-nucleotide polymorphisms (SNP) in several tubular urate transporter genes. No study has assessed the association of reabsorption and secretion urate transporter gene SNP with gout in a single cohort of documented primary patients with gout carefully subclassified as normoexcretors or underexcretors.
  
  
  METHODS
  Three reabsorption SNP (SLC22A12/URAT1, SLC2A9/GLUT9, and SLC22A11/OAT4) and 2 secretion transporter SNP (SLC17A1/NPT1 and ABCG2/BRCP) were studied in 104 patients with primary gout and in 300 control subjects. The patients were subclassified into normoexcretors and underexcretors according to their serum and 24-h urinary uric acid levels under strict conditions of dietary control.
  
  
  RESULTS
  Compared with control subjects, patients with gout showed different allele distributions of the 5 SNP analyzed. However, the diagnosis of underexcretor was only positively associated with the presence of the T allele of URAT1 rs11231825, the G allele of GLUT9 rs16890979, and the A allele of ABCG2 rs2231142. The association of the A allele of ABCG2 rs2231142 in normoexcretors was 10 times higher than in underexcretors. The C allele of NPT1 rs1165196 was only significantly associated with gout in patients with normal uric acid excretion.
  
  
  CONCLUSIONS
  Gout with uric acid underexcretion is associated with transporter gene SNP related mainly to tubular reabsorption, whereas uric acid normoexcretion is associated only with tubular secretion SNP. This finding supports the concept of distinctive mechanisms to account for hyperuricemia in patients with gout with reduced or normal uric acid excretion.
authors.affiliation: From the Department of Biochemistry, Department of Rheumatology, Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital; Department of Epidemiology and Public Health, Madrid Autonoma University, IdiPaz, Madrid, Spain.R.J. Torres, MD, PhD, Department of Biochemistry; E. de Miguel, MD, PhD, Department of Rheumatology; R. Bailén, MD; J.G. Puig, MD, PhD, Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital; J.R. Banegas, MD, PhD, Department of Epidemiology and Public Health, Madrid Autonoma University. rtorres.hulp@salud.madrid.org.
authors.forename: Rosa J
authors.initials: RJ
authors.lastname: Torres
authors.affiliation: From the Department of Biochemistry, Department of Rheumatology, Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital; Department of Epidemiology and Public Health, Madrid Autonoma University, IdiPaz, Madrid, Spain.R.J. Torres, MD, PhD, Department of Biochemistry; E. de Miguel, MD, PhD, Department of Rheumatology; R. Bailén, MD; J.G. Puig, MD, PhD, Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital; J.R. Banegas, MD, PhD, Department of Epidemiology and Public Health, Madrid Autonoma University.
authors.forename: Eugenio
authors.initials: E
authors.lastname: de Miguel
authors.affiliation: From the Department of Biochemistry, Department of Rheumatology, Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital; Department of Epidemiology and Public Health, Madrid Autonoma University, IdiPaz, Madrid, Spain.R.J. Torres, MD, PhD, Department of Biochemistry; E. de Miguel, MD, PhD, Department of Rheumatology; R. Bailén, MD; J.G. Puig, MD, PhD, Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital; J.R. Banegas, MD, PhD, Department of Epidemiology and Public Health, Madrid Autonoma University.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Bailén
authors.affiliation: From the Department of Biochemistry, Department of Rheumatology, Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital; Department of Epidemiology and Public Health, Madrid Autonoma University, IdiPaz, Madrid, Spain.R.J. Torres, MD, PhD, Department of Biochemistry; E. de Miguel, MD, PhD, Department of Rheumatology; R. Bailén, MD; J.G. Puig, MD, PhD, Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital; J.R. Banegas, MD, PhD, Department of Epidemiology and Public Health, Madrid Autonoma University.
authors.forename: José R
authors.initials: JR
authors.lastname: Banegas
authors.affiliation: From the Department of Biochemistry, Department of Rheumatology, Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital; Department of Epidemiology and Public Health, Madrid Autonoma University, IdiPaz, Madrid, Spain.R.J. Torres, MD, PhD, Department of Biochemistry; E. de Miguel, MD, PhD, Department of Rheumatology; R. Bailén, MD; J.G. Puig, MD, PhD, Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital; J.R. Banegas, MD, PhD, Department of Epidemiology and Public Health, Madrid Autonoma University.
authors.forename: Juan G
authors.initials: JG
authors.lastname: Puig
mesh_terms: D000368:Aged; D000483:Alleles; D005260:Female; D006073:Gout / Q000235:genetics* / Q000652:urine; D006801:Humans; D033461:Hyperuricemia / Q000235:genetics* / Q000652:urine; D008297:Male; D008875:Middle Aged; D027361:Organic Anion Transporters / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014527:Uric Acid / Q000652:urine*
chemical_list: D027361:Organic Anion Transporters; C103862:urate transporter; D014527:Uric Acid
keywords: ARTHRITIS; GENE POLYMORPHISM; GOUT