David E. L. Wilcken

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Endothelium–dependent vasodilatation is mediated by release of nitric oxide formed by constitutively expressed endothelial nitric oxide synthase (ecNOS). We explored the distribution of polymorphism ecNOS4a/b in 549 subjects with, and 153 without, coronary artery disease in relation to smoking. In current and ex–cigarette smokers, but not nonsmokers, there(More)
BACKGROUND The results of retrospective and prospective case-control studies have clearly established that mild elevations of the plasma homocysteine level are associated with increased risk of coronary, cerebral, and peripheral vascular disease. Recently, a mutation (677C-->T) was identified in the methylenetetrahydrofolate reductase (MTHFR) gene that(More)
Both markedly and mildly elevated circulating homocysteine concentrations are associated with increased risk of vascular occlusion. Here we review possible mechanisms that mediate these effects. Inborn errors of homocysteine metabolism result in markedly elevated plasma homocysteine (200-300 micromol/L) and thromboembolic (mainly venous) disease: treatment(More)
Among 40 patients with homocystinuria due to cystathionine β-synthase deficiency diagnosed in the state of New South Wales, Australia (population 6 million) and followed long-term, there were 10 deaths at ages 2-30 years. Of these 8 were definite vascular deaths, one was a presumed vascular death, and the other was due to an accident and unrelated to(More)
Homocystinuria, an abnormality of methionine metabolism is associated with severe vascular disease in infancy and childhood. Homocysteine is formed during the metabolism of methionine and accumulations of this and of cysteine-homocysteine mixed disulfide in the plasma indicate a partial block in the methionine degradation pathway. Methionine metabolism was(More)
An inborn error of metabolism, homocystinuria due to cystathionine beta-synthase deficiency, results in markedly elevated levels of circulating homocysteine. Premature vascular events are the main life-threatening complication. Half of all untreated patients have a vascular event by 30 years of age. We performed a multicenter observational study to assess(More)
We recently showed that loss of a MspI restriction site in the 5'-end (intron 1) of the apolipoprotein (apo) AI gene is due to a C to T transition (+83 bp) and/or a G to A transition (+84 bp). Since this region may be relevant to the regulation of apo AI gene expression and therefore to plasma high density lipoprotein cholesterol (HDL-C), we explored the(More)
BACKGROUND DNA variants of the lipoprotein lipase gene are associated with changes in lipid metabolism similar to those in diabetes and may relate to the development of atherosclerotic lesions, particularly premature lesions. METHODS AND RESULTS To determine whether lipoprotein lipase gene variants are relevant to ongoing atherogenesis, we explored(More)
Modest elevations of circulating homocyst(e)ine are common in patients with vascular disease. We explored in normal and coronary artery disease (CAD) populations the distribution of a mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene that results in enzyme thermolability and reduced activity and in homocyst(e)ine elevation to assess its(More)
Nitric oxide (NO) has an important physiological role in regulating vascular tone and is also relevant to many pathological processes including hypertension and atherosclerosis. Endothelial constitutive nitric oxide synthase (ecNOS) is the key enzyme in determining basal vascular wall NO production. We used a combination of maximum-likelihood-based(More)