Homocysteine

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Abstract

The interest in homocysteine has burgeoned during recent years. Homocysteine is now considered a risk factor for several diseases, particularly cardiovascular disease, where elevated levels of the amino acid is associated with increased risk of morbidity and mortality.

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The advent of simple assays has changed homocysteine measurement from a research tool into a standard and routine clinical test. The following sections will discuss the biochemical background, as well as the association between elevated levels of homocysteine and disease.

The History of Homocysteine
Homocysteine was first described by Butz and du Vigneaud in 1932. It is a sulphur-containing amino acid that is closely related to the essential amino acid methionine and to cysteine.

An association between elevated homocysteine levels and human disease was first suggested in 1962 by Carson and Neil, who found high homocysteine concentrations in the urine of some children with mental retardation. The elevated homocysteine levels in these patients were caused by severe enzyme defects blocking the homocysteine metabolism.

This condition, homocystinuria, was later found to be associated with premature occlusive cardiovascular disease, even in childhood, and about 25% of patients died as a result of cardiovascular events before the age of 30.

In 1969, McCully described the vascular pathology in these patients, including smooth muscle proliferation, progressive arterial stenosis and haemostatic changes. During the last 15 years it has been thoroughly documented that also moderately elevated homocysteine levels in serum or plasma is a strong and independent risk factor for occlusive arterial disease, and of venous thrombosis, and also predicts vascular and all-cause mortality. As many as 50% of patients with stroke and other atherothrombotic diseases have high homocysteine levels (greater than 15 micromol per litre (├é┬Ámol/litre)).

In addition, hyperhomocysteinaemia is associated with adverse pregnancy outcome, such as spontaneous early abortion, placental vasculopathy and birth defects. It is not only neural tube defects (NTDs) but also cardiac malformations and cleft lip and/or palate, which are associated with higher homocysteine levels than in controls.

Many studies have also found an association between elevated homocysteine levels and impaired cognitive performance and dementia. Several prospective studies have now shown that folate and/or vitamin B12 status or elevated levels of homocysteine, even within the currently accepted reference range, predisposes for the development of dementia, or increases the rate of disease progress. An association with depression and other neuropsychiatric disorders is also found. There is also much focus on the association between carcinogenesis and impaired homocysteine metabolism./>/>/>/>/>/>/>/>/>/>/>/>/>

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References
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