Increased homocysteine and S-adenosylhomocysteine concentrations and DNA hypomethylation in vascular disease.
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.
Castro
Rita
R
Centro de Patogénese Molecular, Faculdade de Farmácia da Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-039 Lisbon, Portugal.
Rivera
Isabel
I
Struys
Eduard A
EA
Jansen
Erwin E W
EE
Ravasco
Paula
P
Camilo
Maria Ermelinda
ME
Blom
Henk J
HJ
Jakobs
Cornelis
C
Tavares de Almeida
Isabel
I
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
D006710:Homocysteine; D012435:S-Adenosylhomocysteine