News Release

Homocysteine gene implicated in spontaneous cervical artery tears

Peer-Reviewed Publication

American Heart Association

American Heart Association journal report

DALLAS, March 1 – Italian researchers have found strong genetic evidence linking homocysteine to the type of strokes caused by tears in the artery wall, according to a report in the March issue of Stroke: Journal of the American Heart Association.

People in the study with elevated blood levels of homocysteine were significantly more represented in the group of patients with a form of stroke called spontaneous cervical artery dissection (sCAD) than stroke-free control subjects – 64 percent vs. 13.9 percent. In addition, those with sCAD were also three times more likely to have two copies of the "T" version of the C677T MTHFR gene – 36 percent vs. 11 percent – leading researchers to suspect homocysteine’s role may be genetic.

"Increased blood concentration of homocysteine seems to predispose individuals to sCAD," says Alessandro Pezzini, M.D., research assistant in the department of neurology at the University of Brescia, Italy. "Our data also suggests that genetic abnormalities in homocysteine metabolism may be a factor."

Cervical artery dissection (CAD) occurs when the artery from the heart to the brain is cut or torn, allowing blood to rush into the artery lining. Blood clots that form as the body responds to the injury can break away, clogging the artery and causing a stroke when they block the blood flow to the brain.

CAD is estimated to cause 20 percent of ischemic strokes (those caused by a blood clot) in people under age 45. The major symptom of CAD is sudden, excruciating pain on one side of the neck. Although it can be caused by trauma, such as in an automobile accident, more than half the time it is spontaneous, meaning no trauma can be found.

This study focused on 25 patients with sCAD. Researchers compared fasting blood samples collected within 72 hours of symptom onset with samples from 31 non-CAD ischemic stroke patients and 36 subjects without stroke. Researchers also conducted genetic testing to determine variations in the C677T MTHFR gene of these subjects.

Epidemiological studies have shown that too much homocysteine in the blood is related to a higher risk of coronary heart disease, stroke and peripheral vascular disease. Some evidence suggests that homocysteine may have an effect on atherosclerosis by damaging the inner lining of arteries and promoting blood clots, but a direct causal link hasn’t been established. Blood levels of homocysteine are strongly influenced by diet and genetic factors.

"This work not only confirms the association between sCAD and mildly elevated homocysteine, but also demonstrates a significant association with the MTHFR TT genotype,"

says Tobias Brandt, M.D., chairman of neurorehabilitation, and assistant professor at the University of Heidelberg, Germany, who co-authored an editorial accompanying Pezzini’s article.

"The relationship between sCAD and elevated homocysteine seems to be complex, since sCAD is not considered an atherosclerotic disease," says Brandt. Moreover, in the group of non-CAD ischemic stroke patients in the study, no association with the TT MTHFR genotype could be established, Brandt notes.

"An arterial dissection is probably the endpoint of a process of blood vessel wall instability influenced by multiple genetic and environmental factors," says Brandt.

For instance, sCAD is known to be more common in families that have specific diseases in their connective tissue, but even in those families only about 5 percent of the members experience arterial dissections, he explains.

It is conceivable that elevated homocysteine is only a factor in some subtypes of sCAD, the editorial states.

In one of his own studies, Brandt’s group found that a majority of sCAD patients showed abnormalities in their connective tissue even though they had no overt symptoms of connective tissue disease. That indicates that sCAD may be related to abnormalities in the tissue that lines the arteries, he says.

His group is looking for a sCAD patient with a large family available in order to determine more about what causes the disease. Pezzini’s co-authors include: Elisabetta Del Zotto, M.D.; Silvana Archetti, Ph.D.; Riccardo Negrini, M.D.; Paolo Bani, M.D.; Alberto Albertini, M.D.; Mario Grassi, Ph.D.; Deodato Assanelli, M.D.; Roberto Gasparotti, M.D.; Luigi Amedeo Vignolo, M.D.; Mauro Magoni, M.D.; and Alessandro Padovani, M.D., Ph.D. Brandt’s co-author is Caspar Grond-Ginsbach, Ph.D.

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