title: DNA methylation status is not impaired in treated cystathionine beta-synthase (CBS) deficient patients.
abstract: BACKGROUND
  Cystathionine beta-synthase (CBS) deficiency is an inborn error of metabolism that is biochemically characterized by severe hyperhomocysteinemia and homocystinuria. In tissues of mice deficient for CBS it has been demonstrated that global DNA methylation and DNA methylation of the H19 differentially methylated region (DMR) were impaired. In this study we aimed to investigate whether DNA methylation is disturbed in patients with hyperhomocysteinemia due to CBS-deficiency.
  
  
  METHODS
  Genomic DNA was isolated from heparin blood from nine CBS deficient patients that were treated with homomcysteine-lowering therapy and eight healthy controls. Global DNA methylation was measured by liquid chromatography-electrospay ionization-tandem mass spectrometry and gene-specific DNA methylation of the H19 DMR was determined by bisulphite-sequencing.
  
  
  RESULTS
  Homocysteine, AdoMet and AdoHcy levels were significantly elevated, whereas no differences in AdoMet:AdoHcy ratio were observed in plasma of treated CBS deficient patients compared with controls. Global DNA methylation and gene-specific DNA methylation of the H19 DMR was not different between CBS deficient patients and controls.
  
  
  CONCLUSIONS
  We demonstrate that DNA methylation is not impaired in treated CBS deficient patients. Further studies are necessary to investigate the precise role of homocysteine-lowering therapy in relation to DNA methylation in patients with homocystinuria.
authors.affiliation: Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands. sandraheil@planet.nl
authors.forename: Sandra G
authors.initials: SG
authors.lastname: Heil
authors.forename: Niels P
authors.initials: NP
authors.lastname: Riksen
authors.forename: Godfried H
authors.initials: GH
authors.lastname: Boers
authors.forename: Yvo
authors.initials: Y
authors.lastname: Smulders
authors.forename: Henk J
authors.initials: HJ
authors.lastname: Blom
mesh_terms: D002853:Chromatography, Liquid; D003541:Cystathionine beta-Synthase / Q000172:deficiency* / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D019175:DNA Methylation; D006710:Homocysteine / Q000097:blood / Q000378:metabolism; D006712:Homocystinuria / Q000378:metabolism; D006801:Humans; D020138:Hyperhomocysteinemia / Q000378:metabolism*; D012435:S-Adenosylhomocysteine / Q000097:blood / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000097:blood / Q000378:metabolism; D017422:Sequence Analysis, DNA; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D006710:Homocysteine; D012436:S-Adenosylmethionine; D004247:DNA; D012435:S-Adenosylhomocysteine; D003541:Cystathionine beta-Synthase