title: Association between global leukocyte DNA methylation, renal function, carotid intima-media thickness and plasma homocysteine in patients with stage 2-4 chronic kidney disease.
abstract: BACKGROUND
  Patients with chronic kidney disease (CKD) have an increased risk of cardiovascular disease (CVD). Preliminary evidence suggests a role for global DNA hypomethylation in the pathogenesis of atherosclerotic complications in CKD. The aims of this study in patients with stage 2-4 CKD were (1) to assess the association between renal function and DNA methylation, (2) to assess the association between DNA methylation and two markers of atherosclerosis [common carotid intima-media thickness (CCA-IMT)] and brachial artery endothelium-dependent, flow-mediated dilatation (BA-FMD) and (3) to examine the effect of a multi-step treatment strategy on DNA methylation.
  
  
  METHODS
  In the Anti-Oxidant Therapy In Chronic Renal Insufficiency study (ATIC-study), 93 patients with stage 2-4 CKD were included. In a randomized, double-blind, placebo-controlled design, the treatment group received pravastatin to which vitamin E was added after 6 months and homocysteine-lowering B-vitamin therapy after another 6 months. DNA methylation was assessed using tandem mass spectrometry. CCA-IMT and BA-FMD were assessed using B-mode ultrasonography.
  
  
  RESULTS
  At baseline, global DNA methylation was not associated with the estimated glomerular filtration rate (P = 0.32) or with CCA-IMT (P = 0.62) or BA-FMD (P = 0.51). No effect of the treatment strategy including B-vitamin on global DNA methylation was found either in the total study group or within separate strata of homocysteine concentration and renal function.
  
  
  CONCLUSIONS
  In patients with stage 2-4 CKD, global DNA methylation is not associated with renal function or with CCA-IMT or BA-FMD. A treatment strategy that includes B-vitamins did not alter global DNA methylation in these patients. These data do not support the role of DNA hypomethylation in CKD-associated vascular disease in patients with stage 2-4 CKD.
authors.affiliation: Department of Internal Medicine, Institute for Cardiovascular Research, VU University Medical Center, VU University, Amsterdam, The Netherlands. p.nanayakkara@vumc.nl
authors.forename: Prabath W B
authors.initials: PW
authors.lastname: Nanayakkara
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Kiefte-de Jong
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
authors.forename: Frans J
authors.initials: FJ
authors.lastname: van Ittersum
authors.forename: Margreet R
authors.initials: MR
authors.lastname: Olthof
authors.forename: Rob M
authors.initials: RM
authors.lastname: Kok
authors.forename: Henk J
authors.initials: HJ
authors.lastname: Blom
authors.forename: Coen
authors.initials: C
authors.lastname: van Guldener
authors.forename: Piet M
authors.initials: PM
authors.lastname: ter Wee
authors.forename: Yvo M
authors.initials: YM
authors.lastname: Smulders
mesh_terms: D000328:Adult; D002339:Carotid Arteries / Q000473:pathology*; D019175:DNA Methylation; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000008:administration & dosage; D017539:Tunica Intima / Q000473:pathology; D014803:Vitamin B Complex / Q000008:administration & dosage; D014810:Vitamin E / Q000008:administration & dosage
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006710:Homocysteine; D014803:Vitamin B Complex; D014810:Vitamin E; D017035:Pravastatin