丹麦科学家最新研究发现，一种影响铁代谢的普通基因变异后，可使其携带者患中风的风险大大上升。
据英国《新科学家》杂志网络版3月27日报道，丹麦海莱乌大学医院的研究人员发现，这种名为ＨＦＥ的基因一旦发生被称为Ｈ６３Ｄ突变的细微变异，就会导致变异基因携带者血液中的铁元素过量进入细胞，由于这种现象通常不易发现，有些这种基因变异的人还会因此患上肝硬化。
为了研究这种基因变异是否对神经系统有影响，研究人员在丹麦收集了9000人的ＤＮＡ样本，然后跟踪这些人的健康情况长达24年。这期间约有400名参与者出现过大脑缺血性卒中。ＨＦＥ基因变异后会出现不同版本。在156名携带两个ＨＦＥ基因变异版本的参与者中，有１０％在研究期间死于这种中风。相比较，携带一个变异版本或不携带变异版本的参与者中，只有４％死于中风。
研究人员在考虑如年龄、性别和胆固醇水平等因素后推算出，携带两个ＨＦＥ基因变异版本的人患中风的风险比不携带者高１８０％。
这项研究的负责人推测，这种基因发生Ｈ６３Ｄ突变，会使血液中的铁元素过量进入细胞，有可能加快血管内危险血凝块的形成，从而使大脑血液循环中断。不过这一研究还没有发现Ｈ６３Ｄ突变与血管内血凝块形成之间有任何关系。
研究人员认为，对Ｈ６３Ｄ突变进行基因测试有助于发现中风风险较高的人，这些人可及时服用药物如他汀类药物或阿斯匹林，以降低出现血凝块的风险。
英文原文：
Common gene mutation linked to tripled stroke risk
12:05 27 March 2007 NewScientist.com news service Roxanne Khamsi
People with a common gene mutation that affects iron metabolism are nearly three times more likely to suffer stroke, a new study reports. The finding should help doctors identify patients who are most at risk of stroke, enabling them to take preventative measures, the researchers say.
As many as one in four Europeans carry one defective copy of this gene, called HFE. Borge Nordestgaard at Herlev University Hospital in Copenhagen, Denmark, explains that a tiny change in the HFE gene, known as the H63D defect, appears to cause excessive iron uptake from the blood into cells. He adds that while this iron overload usually goes undetected, some people may develop liver cirrhosis late in life as a result.
To see whether this gene had an effect on the nervous system, Nordestgaard and colleagues collected DNA samples from 9000 people in Denmark, and then tracked their health over the course of 24 years. During that period about 400 participants suffered an ischemic stroke – a sudden loss of blood supply to a region of the brain.
Ten per cent of the 156 subjects with two copies of the defective HFE gene died from this type of stroke during the study. By comparison only 4% of people with one or no mutated versions of HFE died from stroke. After adjusting for possible confounding factors such as age, gender and cholesterol levels, researchers calculated that people with two mutated HFE genes had a 180% higher risk of stroke than those with no mutations in the gene.
Missing plaques
Nordestgaard says he expected that the iron overload associated with the H63D mutation may somehow increase the formation of dangerous plaques inside blood vessels, thereby disrupting circulation in the brain. But his team did not find any link between the H63D mutation and symptoms of plaque build-up in the subjects.
"Further research is needed to determine why this gene appears to cause such a significant increased risk of stroke, since our data suggests plaque build-up in the arteries and iron overload are not to blame," he says.
He says that a gene test for the H63D mutation could help encourage patients with stroke risk factors to take drugs such as statins or aspirin to reduce the risk of blood clotting. "If people are told they have a genetic risk they might better stick to their preventative medication."
Daniel Woo at the University of Cincinnati in Ohio, US, says that further research into how the H63D mutation and other gene defects prime the brain for stroke could eventually help drug developers find targets for new preventative medicines.
Journal reference: Neurology (vol 68, p 1025)
