title: Endothelial nitric oxide synthase single nucleotide polymorphism and left ventricular function in early chronic kidney disease.
abstract: BACKGROUND
  Chronic kidney disease (CKD) is associated with accelerated cardiovascular disease and heart failure. Endothelial nitric oxide synthase (eNOS) Glu298Asp single nucleotide polymorphism (SNP) genotype has been associated with a worse phenotype amongst patients with established heart failure and in patients with progression of their renal disease. The association of a cardiac functional difference in non-dialysis CKD patients with no known previous heart failure, and eNOS gene variant is investigated.
  
  
  METHODS
  140 non-dialysis CKD patients, who had cardiac magnetic resonance (CMR) imaging and tissue doppler echocardiography as part of two clinical trials, were genotyped for eNOS Glu298Asp SNP retrospectively.
  
  
  RESULTS
  The median estimated glomerular filtration rate (eGFR) was 50 mls/min and left ventricular ejection fraction (LVEF) was 74% with no overt diastolic dysfunction in this cohort. There were significant differences in LVEF across eNOS genotypes with GG genotype being associated with a worse LVEF compared to other genotypes (LVEF: GG 71%, TG 76%, TT 73%, p = 0.006). After multivariate analysis, (adjusting for age, eGFR, baseline mean arterial pressure, contemporary CMR heart rate, total cholesterol, high sensitive C-reactive protein, body mass index and gender) GG genotype was associated with a worse LVEF, and increased LV end-diastolic and systolic index (p = 0.004, 0.049 and 0.009 respectively).
  
  
  CONCLUSIONS
  eNOS Glu298Asp rs1799983 polymorphism in CKD patients is associated with relevant sub-clinical cardiac remodelling as detected by CMR. This gene variant may therefore represent an important genetic biomarker, and possibly highlight pathways for intervention, in these patients who are at particular risk of worsening cardiac disease as their renal dysfunction progresses.
authors.affiliation: Department of Nephrology, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2WB, United Kingdom; Centre for Translational Inflammation Research, University of Birmingham, Birmingham, B15 2WB, United Kingdom.
authors.forename: Sourabh
authors.initials: S
authors.lastname: Chand
authors.affiliation: Department of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2WB, United Kingdom.
authors.forename: Colin D
authors.initials: CD
authors.lastname: Chue
authors.affiliation: Department of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2WB, United Kingdom.
authors.forename: Nicola C
authors.initials: NC
authors.lastname: Edwards
authors.affiliation: Department of Statistics, Wolfson Laboratory, Old Queen Elizabeth Hospital, Birmingham, B15 2TH, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Hodson
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Headington, Oxford, OX3 7LJ, United Kingdom.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Simmonds
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Headington, Oxford, OX3 7LJ, United Kingdom.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hamilton
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Headington, Oxford, OX3 7LJ, United Kingdom; Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, OX3 7LG, United Kingdom.
authors.forename: Stephen C L
authors.initials: SC
authors.lastname: Gough
authors.affiliation: Department of Nephrology, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2WB, United Kingdom; Centre for Translational Inflammation Research, University of Birmingham, Birmingham, B15 2WB, United Kingdom.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Harper
authors.affiliation: Department of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2WB, United Kingdom.
authors.forename: Rick P
authors.initials: RP
authors.lastname: Steeds
authors.affiliation: Department of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2WB, United Kingdom.
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Townend
authors.affiliation: Department of Nephrology, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2WB, United Kingdom.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Ferro
authors.affiliation: Department of Nephrology, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2WB, United Kingdom; Centre for Translational Inflammation Research, University of Birmingham, Birmingham, B15 2WB, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Borrows
mesh_terms: D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D018618:Echocardiography, Doppler, Color; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011859:Radiography; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D016277:Ventricular Function, Left
chemical_list: D002097:C-Reactive Protein; D002784:Cholesterol; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III