title: Increased homocysteine and S-adenosylhomocysteine concentrations and DNA hypomethylation in vascular disease.
abstract: 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.
  
  
  CONCLUSIONS
  Global DNA methylation may be altered in vascular disease, with a concomitant increase in plasma tHcy and AdoHcy.
authors.affiliation: Centro de Patogénese Molecular, Faculdade de Farmácia da Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-039 Lisbon, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Castro
authors.forename: Isabel
authors.initials: I
authors.lastname: Rivera
authors.forename: Eduard A
authors.initials: EA
authors.lastname: Struys
authors.forename: Erwin E W
authors.initials: EE
authors.lastname: Jansen
authors.forename: Paula
authors.initials: P
authors.lastname: Ravasco
authors.forename: Maria Ermelinda
authors.initials: ME
authors.lastname: Camilo
authors.forename: Henk J
authors.initials: HJ
authors.lastname: Blom
authors.forename: Cornelis
authors.initials: C
authors.lastname: Jakobs
authors.forename: Isabel
authors.initials: I
authors.lastname: Tavares de Almeida
mesh_terms: D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics*; D019175:DNA Methylation; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012435:S-Adenosylhomocysteine / Q000097:blood
chemical_list: D006710:Homocysteine; D012435:S-Adenosylhomocysteine