Scientists at deCODE genetics (Nasdaq:DCGN) and academic colleagues from the United States today report the discovery of a common genetic variant that confers increased risk of myocardial infarction (MI), or heart attack. The variant, a SNP (a single-letter variant in the genome) on chromosome 9p21, was discovered through genome-wide SNP analysis in Iceland and replicated in three cohorts of European descent from Philadelphia, Atlanta and Durham, North Carolina. Of more than 17,000 patients and control subjects in the study, more than 20% of participants carry two copies of the variant, corresponding to a more than 60% increase in risk of heart attack compared to those without the variant. Moreover, in early onset cases – men and women who suffered a heart attack before the ages of 50 and 60, respectively – carrying two copies of the variant corresponds to an approximate doubling of risk compared to non-carriers. The variant is estimated to account for approximately one-fifth of the incidence of heart attack in populations of European origin, and nearly one third of early-onset cases, making it the one of the most significant genetic risk factors found to date for heart attack as a public health problem.
The paper, entitled “A common Variant on Chromosome 9p21 Affects the Risk of Myocardial Infarction,” is published today in the online edition of Science, and will appear in an upcoming printed edition of the journal.
deCODE scientists began the study by genotyping a large group of Icelandic heart patients and controls with the Illumina HumanHap300 gene chip, which captures more than 300,000 SNPs across the genome. This analysis yielded several markers significantly associated with the disease, and the deCODE team then utilized data from the international HapMap project to identify additional SNPs not on the gene chip but which correlated with those identified in the first analysis. This yielded a SNP, called rs10757278, with the highest association to the disease, and which was replicated in all of the cohorts. This SNP lies within a block of the genome containing two well know tumor supressor genes, CDKN2A and CDKN2B. The proteins encoded by these genes are also involved in cell proliferation, cell aging and apoptosis. These processes are important in atherogenesis, the development of plaques within arteries, a hallmark of coronary artery disease and a precursor to heart attack.
deCODE plans to bundle this discovery with other genetic variants it has linked to risk of heart attack into a DNA-based test for gauging inherited risk of MI. The company believes that such a test, particularly for those with a strong family history of heart attack or early onset heart attack, as well as those with other risk factors, may enable individuals and their doctors to adopt more informed and thus potentially more effective prevention regimes. deCODE will also continue to study the function of these variants to better understand the means by which these variants confer risk. This information may enable the identification of drug targets for the development of compounds to counteract the biological effects of these variants and thereby prevent heart attack.