BACKGROUND: The pathogenic mechanism of homocysteine's effect on cardiovascular risk is poorly understood. Recent studies show that DNA hypomethylation induced by increases in S-adenosylhomocysteine (AdoHcy), an intermediate of Hcy metabolism and a potent inhibitor of methyltransferases, may be involved in homocysteine-related pathology. METHODS: We measured fasting plasma total Hcy (tHcy), AdoHcy, and S-adenosylmethionine (AdoMet) and methylation in leukocytes in 17 patients with vascular disease and in 15 healthy, age- and sex-matched controls. RESULTS: Patient with vascular disease had significantly higher plasma tHcy and AdoHcy concentrations and significantly lower plasma AdoMet/AdoHcy ratios and genomic DNA methylation. AdoMet concentrations were not significantly different between the two groups. More than 50% of the patients fell into the highest quartiles of plasma tHcy, AdoHcy, and [(3)H]dCTP incorporation/ micro g of DNA (meaning the lowest quartile of DNA methylation status) and into the lowest quartile of the AdoMet/AdoHcy ratios of the control group. Plasma tHcy was significantly correlated with plasma AdoHcy and AdoMet/AdoHcy ratios (n = 32; P < 0.001). DNA methylation status was significantly correlated with plasma tHcy and AdoHcy (n = 32; P < 0.01) but not with plasma AdoMet/AdoHcy ratios. CONCLUSION: Global DNA methylation may be altered in vascular disease, with a concomitant increase in plasma tHcy and AdoHcy.
BACKGROUND: The pathogenic mechanism of homocysteine's effect on cardiovascular risk is poorly understood. Recent studies show that DNA hypomethylation induced by increases in S-adenosylhomocysteine (AdoHcy), an intermediate of Hcy metabolism and a potent inhibitor of methyltransferases, may be involved in homocysteine-related pathology. METHODS: We measured fasting plasma total Hcy (tHcy), AdoHcy, and S-adenosylmethionine (AdoMet) and methylation in leukocytes in 17 patients with vascular disease and in 15 healthy, age- and sex-matched controls. RESULTS:Patient with vascular disease had significantly higher plasma tHcy and AdoHcy concentrations and significantly lower plasma AdoMet/AdoHcy ratios and genomic DNA methylation. AdoMet concentrations were not significantly different between the two groups. More than 50% of the patients fell into the highest quartiles of plasma tHcy, AdoHcy, and [(3)H]dCTP incorporation/ micro g of DNA (meaning the lowest quartile of DNA methylation status) and into the lowest quartile of the AdoMet/AdoHcy ratios of the control group. Plasma tHcy was significantly correlated with plasma AdoHcy and AdoMet/AdoHcy ratios (n = 32; P < 0.001). DNA methylation status was significantly correlated with plasma tHcy and AdoHcy (n = 32; P < 0.01) but not with plasma AdoMet/AdoHcy ratios. CONCLUSION: Global DNA methylation may be altered in vascular disease, with a concomitant increase in plasma tHcy and AdoHcy.
Authors: Stepan Melnyk; George J Fuchs; Eldon Schulz; Maya Lopez; Stephen G Kahler; Jill J Fussell; Jayne Bellando; Oleksandra Pavliv; Shannon Rose; Lisa Seidel; David W Gaylor; S Jill James Journal: J Autism Dev Disord Date: 2012-03
Authors: Zhong-Zheng Zhu; Lifang Hou; Valentina Bollati; Letizia Tarantini; Barbara Marinelli; Laura Cantone; Allen S Yang; Pantel Vokonas; Jolanta Lissowska; Silvia Fustinoni; Angela C Pesatori; Matteo Bonzini; Pietro Apostoli; Giovanni Costa; Pier Alberto Bertazzi; Wong-Ho Chow; Joel Schwartz; Andrea Baccarelli Journal: Int J Epidemiol Date: 2010-09-15 Impact factor: 7.196
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