title: Caveolin-1 single-nucleotide polymorphism and arterial stiffness in non-dialysis chronic kidney disease.
abstract: Arteriosclerosis is an independent predictor of increased cardiovascular mortality in chronic kidney disease (CKD). Histologically it is characterized by hypertrophy and fibrosis of the arterial media wall leading to increased arterial stiffness and end-organ damage. Caveolin-1 acts as an intracellular signalling pathway chaperone in human fibrotic and vascular diseases. The purpose of this study was to assess the association between caveolin-1 (CAV1) single-nucleotide polymorphism (SNP) rs4730751 and arterial stiffness as measured by arterial pulse wave velocity (PWV) in an early-stage CKD cohort and in a cohort with more severe CKD.
  
  
  
  Two prospectively maintained patient cohorts with non-dialysis CKD were studied: 144 patients in the Chronic Renal Impairment in Birmingham (CRIB) cohort and 147 patients in the Renal Impairment in Secondary Care (RIISC) cohort, with matched exclusion criteria and DNA sampling availability. At entry to each cohort database, each patient's initial arterial PWV was measured, as well as their anthropomorphic and biochemical data. CAV1 rs4730751 SNP genotyping was performed using Taqman technology.
  
  
  
  The CAV1 rs4730751 SNP CC genotype was associated with lower arterial PWV in both CRIB early stage CKD patients [8.1 versus 8.6 m/s; coefficient -0.780 (-1.412, -0.149); P = 0.016] and RIISC more advanced stage CKD patients [8.7 versus 9.4 m/s; coefficient -0.695 (-1.288, -0.102); P = 0.022]; these relationships held following adjustment for other important confounders.
  
  
  
  This replicated study suggests potential utility of the studied CAV1 SNP as a genetic biomarker in CKD and a role for CAV1 in the development of arteriosclerosis in this setting. Further studies are warranted to further explore the basic science driving these clinical observations.
authors.affiliation: Department of Renal Medicine, Queen Elizabeth Hospital Birmingham, Birmingham, UK Centre for Translational Inflammation Research, University of Birmingham, Birmingham, UK.
authors.forename: Sourabh
authors.initials: S
authors.lastname: Chand
authors.affiliation: Department of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham, UK.
authors.forename: Nicola C
authors.initials: NC
authors.lastname: Edwards
authors.affiliation: Department of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham, UK.
authors.forename: Colin D
authors.initials: CD
authors.lastname: Chue
authors.affiliation: Department of Renal Medicine, Queen Elizabeth Hospital Birmingham, Birmingham, UK Centre for Translational Inflammation Research, University of Birmingham, Birmingham, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Jesky
authors.affiliation: Department of Renal Medicine, Queen Elizabeth Hospital Birmingham, Birmingham, UK Centre for Translational Inflammation Research, University of Birmingham, Birmingham, UK.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Stringer
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Simmonds
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Duff
authors.affiliation: Department of Renal Medicine, Queen Elizabeth Hospital Birmingham, Birmingham, UK Centre for Translational Inflammation Research, University of Birmingham, Birmingham, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Cockwell
authors.affiliation: Department of Renal Medicine, Queen Elizabeth Hospital Birmingham, Birmingham, UK Centre for Translational Inflammation Research, University of Birmingham, Birmingham, UK.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Harper
authors.affiliation: Department of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham, UK.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Steeds
authors.affiliation: Department of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham, UK.
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Townend
authors.affiliation: Department of Renal Medicine, Queen Elizabeth Hospital Birmingham, Birmingham, UK Centre for Translational Inflammation Research, University of Birmingham, Birmingham, UK.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Ferro
authors.affiliation: Department of Renal Medicine, Queen Elizabeth Hospital Birmingham, Birmingham, UK Centre for Translational Inflammation Research, University of Birmingham, Birmingham, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Borrows
mesh_terms: D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000175:diagnosis / Q000235:genetics*; D051242:Caveolin 1 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D063177:Pulse Wave Analysis; D051436:Renal Insufficiency, Chronic / Q000235:genetics*; D059289:Vascular Stiffness / Q000235:genetics
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1
keywords: arterial stiffness; caveolin-1; chronic kidney disease; pulse wave velocity; single-nucleotide polymorphism