title: A genetic marker of uric acid level, carotid atherosclerosis, and arterial stiffness: a family-based study.
abstract: BACKGROUND
  Hyperuricemia associates with atherosclerosis complications, but it is uncertain whether this relationship is causal in nature. The urate transporter GLUT9 (encoded by the SLC2A9 gene) is a major genetic determinant of serum uric acid level in humans. Because polymorphisms are distributed randomly at mating (Mendelian randomization), studies based on GLUT9 polymorphisms may provide unconfounded assessment of the nature of the link between uric acid and atherosclerosis.
  
  
  METHODS
  Cross-sectional study.
  
  
  METHODS
  Family-based study including 449 individuals in 107 families in a genetically homogeneous population in Southern Italy.
  
  
  METHODS
  Serum uric acid level, rs734553 allele, and age.
  
  
  RESULTS
  Ultrasound biomarkers of atherosclerosis (intima-media thickness [IMT] and internal diameter) and pulse wave velocity (PWV).
  
  
  RESULTS
  Serum uric acid level was dose-dependently associated with the T allele of rs734553, a polymorphism in SLC2A9 (P=8×10(-6)). Serum uric acid level was a strong modifier of the relationship between age and IMT in fully adjusted analyses (β=0.33; P=0.01), whereas no such relationship was found for internal diameter (β=-0.15; P=0.3) or PWV (β=0.10; P=0.6). The T allele coherently associated with carotid IMT, internal diameter, and PWV and emerged as an even stronger modifier of the age-IMT and age-internal diameter relationships in both crude and fully adjusted (β=0.40 [P<0.001] and β=0.48 [P=0.003], respectively) analyses.
  
  
  CONCLUSIONS
  This is a hypothesis-generating study.
  
  
  CONCLUSIONS
  Results in this family-based study implicate uric acid as an important modifier of the age-dependent risk for atherosclerosis. Trials testing uric acid-lowering interventions are needed to prove this hypothesis.
authors.affiliation: CNR-IFC/IBIM, Reggio Calabria, Italy; Unità Operativa di Nefrologia, Ipertensione e Trapianto Renale Ospedali Riuniti, Reggio Cal, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mallamaci
authors.affiliation: CNR-IFC/IBIM, Reggio Calabria, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Testa
authors.affiliation: CNR-IFC/IBIM, Reggio Calabria, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Leonardis
authors.affiliation: CNR-IFC/IBIM, Reggio Calabria, Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Tripepi
authors.affiliation: CNR-IFC/IBIM, Reggio Calabria, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pisano
authors.affiliation: CNR-IFC/IBIM, Reggio Calabria, Italy.
authors.forename: Belinda
authors.initials: B
authors.lastname: Spoto
authors.affiliation: CNR-IFC/IBIM, Reggio Calabria, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Sanguedolce
authors.affiliation: CNR-IFC/IBIM, Reggio Calabria, Italy.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Parlongo
authors.affiliation: CNR-IFC/IBIM, Reggio Calabria, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tripepi
authors.affiliation: CNR-IFC/IBIM, Reggio Calabria, Italy; Unità Operativa di Nefrologia, Ipertensione e Trapianto Renale Ospedali Riuniti, Reggio Cal, Italy. Electronic address: carmine.zoccali@tin.it.
authors.forename: Carmine
authors.initials: C
authors.lastname: Zoccali
mesh_terms: D000328:Adult; D000483:Alleles; D015415:Biomarkers / Q000097:blood; D002340:Carotid Artery Diseases / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D059168:Carotid Intima-Media Thickness; D003430:Cross-Sectional Studies; D005260:Female; D005819:Genetic Markers / Q000502:physiology*; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D006801:Humans; D033461:Hyperuricemia / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors; D014527:Uric Acid / Q000097:blood*; D059289:Vascular Stiffness / Q000235:genetics / Q000502:physiology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; D051246:Glucose Transport Proteins, Facilitative; C411811:SLC2A9 protein, human; D014527:Uric Acid
keywords: Atherosclerosis; SLC2A9; cardiovascular disease; glucose transporter type 9 (GLUT9); hyperuricemia; intima-media thickness (IMT); pulse-wave velocity (PWV); rs734553; uric acid