March 26, 2007 / 8:57 PM / in 12 years

Hemochromatosis gene linked to stroke risk

NEW YORK (Reuters Health) - Patients with a specific gene variation for hereditary hemochromatosis, an autosomal recessive disease associated with increased iron accumulation, have more than double the risk of stroke, new research suggests.

Hemochromatosis affects how the body metabolizes iron, which results an iron build-up in the liver. Without treatment, the condition causes liver enlargement that can lead to cirrhosis or liver cancer. The disease can also cause diabetes, heart disease, arthritis, and other serious conditions.

The study, which is reported in the journal Neurology, focused on two variations in the hemochromatosis gene — H63D and C282Y. Of all the various combinations of these mutations, only patients with two copies of H63D had a significantly increased risk of cerebrovascular disease and ischemic stroke, a stroke caused by a blockage in an artery in the brain, which cuts off the blood supply.

“This type of gene has previously been associated with brain diseases such as Alzheimer’s disease, Parkinson disease, ALS, multiple sclerosis, and cerebrovascular disease, but this is the first time we’ve been able to determine this gene predicts such a significant increased risk of stroke,” senior author Borge G. Nordestgaard, from Herlev University Hospital in Denmark, said in a statement.

The findings stem from two studies. The first included 701 patients who had symptoms of atherosclerosis, or “hardening of the arteries,” in the carotid artery, an artery that carries blood from the heart to the brain, and 2777 patients without this condition.

The second study included 9178 subjects who were followed for 24 years. During follow-up, 504 of these subjects developed ischemic carotid atherosclerosis, including 393 with ischemic stroke.

The hemochromatosis gene types were not consistently associated with the risk of symptomatic carotid atherosclerosis, the findings indicate.

However, two copies of the H63D gene increased the risk of ischemic cerebrovascular disease by 2.1-fold and the risk of ischemic stroke by 2.8-fold. By contrast, individuals with hemochromatosis with other gene patterns did not have an increase in either of these risks.

“Further research is needed to determine why this gene appears to cause such a significant increased risk of stroke, since our data suggest plaque build-up in the arteries and iron overload are not to blame,” Nordestgaard said.

SOURCE: Neurology, March 27, 2007.

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