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Not only lipids and inflammation: Insight into a new cause of heart attack and other vascular disease

08 Jan 2008 - deCODE scientists report that the genetic variant on chromosome 9p21 that the company has linked to increased risk of heart attack is also associated with up to 70% increase in risk of abdominal aortic aneurysm (AAA) and intracranial aneurysm (IA). This is the first common genetic variant ever found to associate with either condition. The paper, entitled 'The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm,' is published in Nature Genetics.
 
AAA and IA are the most common aneurysms - balloon-like protrusions on arteries in the abdomen and head, respectively - and are potentially lethal if they are left untreated and burst. "Today's findings enhance the importance of our 9p21 variant when it comes to risk of cardiovascular disease, and suggest that it confers this risk by affecting how artery walls respond to other risk factors such as atherosclerotic plaque and inflammation," said Kari Stefansson, CEO of deCODE. "As we bring these findings into our cardiovascular therapeutics program, we are also incorporating them into our deCODE MI diagnostic test and our deCODEme(TM) personal genome analysis service. With today's discovery and others we expect to announce in the weeks and months ahead, we underscore our global leadership in human genetics and our commitment to convert this leadership into products and the products into profit for our shareholders."
 
Six months ago, deCODE reported that this SNP confers significantly increased risk of coronary artery disease (CAD) and accounts for roughly one-third of early-onset heart attacks. This discovery has now been replicated in studies of ten populations. The study published today was aimed in part at investingating how this risk is conferred. To do so, the deCODE team, - enlisting the participation of academic researchers and thousands of their patients from Iceland, New Zealand, the Netherlands, Finland, the US, Belgium, Sweden, Italy, Denmark and the UK - analyzed the association of the variant with several other cardiovascular conditions. The results show that the 'G' allele is suggestively but not definitively associated with conditions involving the buildup of atherosclerotic plaque, including peripheral artery disease and large artery stroke. However those with one copy of this version of the SNP had a more than 30% greater risk of both AAA and IA than non-carriers. Those with two copies - that is, who inherited the risk variant form both parents - were at more than 70% greater risk of both AAA and IA than were non-carriers. What heart attack and these types of aneurysm have in common is that all three can result from an abnormal or deficient remodeling and/or repair of vessel walls.