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. CONCLUSION: 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.
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 deficientpatients 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 deficientpatients compared with controls. Global DNA methylation and gene-specific DNA methylation of the H19 DMR was not different between CBS deficientpatients and controls. CONCLUSION: We demonstrate that DNA methylation is not impaired in treated CBS deficientpatients. Further studies are necessary to investigate the precise role of homocysteine-lowering therapy in relation to DNA methylation in patients with homocystinuria.
Authors: Melissa B Glier; Ying F Ngai; Dian C Sulistyoningrum; Rika E Aleliunas; Teodoro Bottiglieri; Angela M Devlin Journal: Epigenetics Date: 2012-12-05 Impact factor: 4.528
Authors: Viktor Kozich; Jitka Sokolová; Veronika Klatovská; Jakub Krijt; Miroslav Janosík; Karel Jelínek; Jan P Kraus Journal: Hum Mutat Date: 2010-07 Impact factor: 4.878
Authors: Pooja R Mandaviya; Roby Joehanes; Dylan Aïssi; Brigitte Kühnel; Riccardo E Marioni; Vinh Truong; Lisette Stolk; Marian Beekman; Marc Jan Bonder; Lude Franke; Christian Gieger; Tianxiao Huan; M Arfan Ikram; Sonja Kunze; Liming Liang; Jan Lindemans; Chunyu Liu; Allan F McRae; Michael M Mendelson; Martina Müller-Nurasyid; Annette Peters; P Eline Slagboom; John M Starr; David-Alexandre Trégouët; André G Uitterlinden; Marleen M J van Greevenbroek; Diana van Heemst; Maarten van Iterson; Philip S Wells; Chen Yao; Ian J Deary; France Gagnon; Bastiaan T Heijmans; Daniel Levy; Pierre-Emmanuel Morange; Melanie Waldenberger; Sandra G Heil; Joyce B J van Meurs Journal: PLoS One Date: 2017-10-30 Impact factor: 3.240