Plasma S -adenosylhomocysteine is a more sensitive indicator of cardiovascular disease than plasma homocysteine

Kerins, David M.; Koury, Mark J.; Capdevila, Antonieta; Rana, Sarvadaman; Wagner, Conrad

doi:10.1093/ajcn/74.6.723

Cited by 156 publications

(109 citation statements)

References 32 publications

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“…The results, shown in Table 1, were consistent with those in fresh control samples established in our laboratory 14 and with data from other laboratories, 9,12,[15][16][17][18] including studies that used specimens stored for several years. 10,19 The sole problem occurred with AdoHcy; our control sera produced abnormally high mean values and wide variations among samples.…”

Section: Laboratory Methodssupporting

confidence: 88%

“…The difficulty of studying adequate numbers of patients with the relatively uncommon disease of pernicious anemia, especially the minority who have neurologic dysfunction, is exacerbated by the need to test them before they are treated and by the many exclusion criteria necessary for study of the issues they raise. Our resultant dependence on less than ideal specimens was partially addressed in several ways: (1) Results in control sera that were processed and stored like the test samples closely matched our 13 and others' reference ranges 9,12,[15][16][17][18] in freshly obtained samples; the sole exception was AdoHcy, which was therefore not included. (2) Experiments on sample-processing variations identified no relevant artifacts (see "Patients, materials, and methods").…”

Section: Transsulfuration and Related Thiol Metabolismmentioning

confidence: 99%

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Cobalamin deficiency with and without neurologic abnormalities: differences in homocysteine and methionine metabolism

Carmel

Melnyk

James

2003

Blood

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The unknown biochemical basis for neurologic dysfunction in cobalamin deficiency and the frequent divergence between neurologic and hematologic manifestations led us to study homocysteine metabolism in 22 patients with pernicious anemia. Serum levels of total homocysteine (tHcy), methionine, S-adenosylmethionine (AdoMet), cysteine, cysteinylglycine (cys-gly), and glutathione (GSH) were measured. Only levels of tHcy and cysteine were increased and only GSH was decreased in cobalamin deficiency as a whole, compared with 17 control subjects. AdoMet correlated only with methionine levels (P ‫؍‬ .015) and cysteine only with cys-gly (P ‫؍‬ .007) in healthy subjects, but in cobalamin-deficient patients AdoMet correlated instead with cysteine, cys-gly, and folate levels only (P ‫؍‬ .008, P ‫؍‬ .03, and P ‫؍‬ .03, respectively). Significant differences appeared in clinically subgrouped cobalamin-deficient patients. The 11 patients with neurologic defects had higher mean levels of folate (

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Section: Laboratory Methodssupporting

confidence: 88%

Section: Transsulfuration and Related Thiol Metabolismmentioning

confidence: 99%

Cobalamin deficiency with and without neurologic abnormalities: differences in homocysteine and methionine metabolism

Carmel

Melnyk

James

2003

Blood

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“…The relation between Hcy and hypomethylation has become a topic of utmost interest because the hypomethylation of many tissue components, including proteins, DNA, RNA, phospholipids, and small molecules, is one important mechanism by which Hcy may be cytotoxic [10]. In this respect a cause-control study showed that plasma AdoHcy concentration was a better predictor of cardiovascular diseases than plasma homocysteine [7].…”

Section: Introductionmentioning

confidence: 99%

Homocysteine‐induced endothelial cell adhesion is related to adenosine lowering and is not mediated by S‐adenosylhomocysteine

et al. 2007

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Hyperhomocysteinemia is a cardiovascular risk factor and may contribute to the pathogenesis of atherosclerosis by altering endothelial functions. The mechanism of homocysteine-induced cell adhesion has been here investigated using EA.hy 926 cells. Homocysteine induces a stereospecific, time-and dosedependent cell adhesion which is prevented by adenosine. The dramatic increase of S-adenosylhomocysteine induced by adenosine-2 0 ,3 0 -dialdehyde does not cause cell adhesion, indicating that no apparent relationship exists between this process and intracellular S-adenosylhomocysteine content. Homocysteine-induced cell adhesion is abolished by pre-treatment with adenosine-2 0 ,3 0 -dialdehyde, demonstrating that the adenosine depletion caused by reversal of S-adenosylhomocysteine hydrolase reaction is responsible for homocysteine-induced cell damage.

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“…The AHCY gene has been assigned to chromosome 20cen-q13.1 (Ensembl locus 20q11. 22) and consists of 10 exons spanning about 23 kb. Native human AHCY is a cytosolic protein composed of four identical subunits and requires NAD þ as a cofactor.…”

Section: Introductionmentioning

confidence: 99%

Effect of genetic variation in the human S-adenosylhomocysteine hydrolase gene on total homocysteine concentrations and risk of recurrent venous thrombosis

Gellekink¹,

Heijer²,

Kluijtmans³

et al. 2004

Eur J Hum Genet

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Hyperhomocysteinemia is an independent and graded risk factor for arterial vascular disease and venous thrombosis. It is still debated via which mechanism homocysteine (Hcy) causes vascular disease. Sadenosylhomocysteine hydrolase (AHCY) catalyses the reversible hydrolysis of S-adenosylhomocysteine (AdoHcy) to Hcy. As an increase in AdoHcy, a strong inhibitor of many methyltransferases, is observed in hyperhomocysteinemic individuals, AdoHcy may play a role in the development of cardiovascular diseases by inhibiting transmethylation reactions. We sequenced the entire coding region and parts of the untranslated regions (UTRs) of the AHCY gene of 20 patients with recurrent venous thrombosis in order to identify genetic variation within this gene. We identified three sequence variants in the AHCY gene: a C4T transition in the 5 0 UTR (À34 bp C4T), a missense mutation in exon 2, which mandates an amino-acid conversion at codon 38 (112 C4T; Arg38Trp) and a silent mutation in exon 4 (390 C4T; Asp130Asp). We studied the effect of the first two variants on total plasma Hcy and venous thrombosis risk in a case -control study on recurrent venous thrombosis. The two polymorphisms under study seem to have no evident effect on tHcy. The adjusted relative risk of venous thrombosis associated with the 112CT genotype compared with 112CC individuals was 1.27 (95% CI 0.55 -2.94), whereas the À34CT genotype confers a risk of 1.25 (95% CI 0.44-3.52) compared with the wild-type genotype at this locus. However, the wide confidence intervals do not allow firm conclusions to be drawn.

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Plasma S -adenosylhomocysteine is a more sensitive indicator of cardiovascular disease than plasma homocysteine

Cited by 156 publications

References 32 publications

Cobalamin deficiency with and without neurologic abnormalities: differences in homocysteine and methionine metabolism

Cobalamin deficiency with and without neurologic abnormalities: differences in homocysteine and methionine metabolism

Homocysteine‐induced endothelial cell adhesion is related to adenosine lowering and is not mediated by S‐adenosylhomocysteine

Effect of genetic variation in the human S-adenosylhomocysteine hydrolase gene on total homocysteine concentrations and risk of recurrent venous thrombosis

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