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.
