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International study identifies gene variants associated with early heart attack
Date:2/8/2009

a gene chip developed by Altshuler's team that can simulaneously screen for SNPs and for copy-number variants deletions or duplications of gene segments, a type of change associated with several disease categories. After analysis of the consortium's samples identified SNPs that could be associated with heart attack risk, the researchers ran replication screens in three independent groups of samples, resulting in a total of 13,000 heart attack patients and 13,000 controls.

Significant associations with the risk of early-onset heart attacks were found for common SNPs in nine genetic regions. Three of those associations with heart attack risk were identified for the first time; and one of the novel regions also had been found, in a separate study by O'Donnell, to promote the buildup of atherosclerotic plaque in the coronary arteries. To analyze the effect of inheriting several risk-associated SNPs, participants were assigned a genotype score, which revealed that those with the highest number of risk-associated variants had more than twice the risk of an early-onset heart attack as those with the fewest. No risk associations were identified with copy-number variants.

Although the increased risk associated with individual SNPs is small, knowledge gained from the association could prove extremely valuable. "One of the known variants we identified is at a gene called PCSK9, which was originally identified in 2003," explains Kathiresan, an assistant professor of Medicine at Harvard Medical School. "Extensive study of that gene region has led to significant insight into the biology of atherosclerosis and heart attack and to efforts to develop targeted drugs. We are optimistic that investigating the mechanics of the newly mapped variants could yield similar insights. And since we already have effective ways to reduce heart-attack risk, individuals at higher genetic risk may benefit from earlier intervention, something that needs to be tested in fu
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
Source:Eurekalert

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