The MI doesn't fall far from the
LGALS2 gene plays a crucial role
in myocardial infarction risk
As a teen, Ken Burrow was a self-avowed
fast food junky. But when his dad dropped dead at 57
from a heart attack, Ken decided to stick to the straight
and narrow as far as diet and exercise were concerned.
So when he had a heart attack at 39, he felt let down
after all, his lifestyle choices had been exemplary.
Cardiology is one of the last bastions of medicine to
resist the onrush of genetics but it turns out that
there may be more to who gets a heart attack than just
diet and exercise. Scientists from the Institute of
Physical and Chemical Research in Tokyo have pinpointed
a gene that seems to play a crucial role in heart attacks.
The results of their study appeared in the May 6 issue
Linking the gene to heart disease
involves some pretty intricate connections. It all starts
with the fact that inflammation leads to atherosclerosis.
Earlier studies had shown that an inflammation-mediating
molecule, lymphotoxin-alpha (LTA), was associated with
a higher risk of heart attack. This led to interest
in another inflammation-implicated protein called galectin-2,
which binds to LTA and controls how much LTA finds its
way into the bloodstream.
Now, how much galectin-2 is made
is controlled by yet another gene, this one called LGALS2.
When researchers analyzed DNA samples from 5,100 subjects,
of whom roughly half had suffered a previous heart attack,
they found that heart attack patients were 34% more
likely to carry a mutation in the LGALS2 gene. This
mutation led to a change in how much galectin-2 was
being made. In theory, this could lead to a change in
LTA levels, which in turn could lead to more inflammation
and a higher risk of myocardial infarction (MI).
The researchers added support to
their theory by showing that galectin-2 and LTA are
present in atherosclerotic plaques but not in adjacent
normal medial smooth muscle cells.
"Decreased expression of galectin-2
might be protective against the risk of MI, so drugs
that can reduce the function of galectin-2 can be therapeutic,"
said lead author Dr Toshihiro Tanaka.
This research can be seen as part
of the growing trend towards viewing heart attack as
a chronic disease process rather than an inevitable
result. Given the tendency for heart disease to run
in families, this change of focus was perhaps overdue.
Smoking, drinking, lounging about
and overeating remain factors, of course, admitted Dr
Tanaka, but now genetic factors may be added to the
long list of cardiac risk factors. He went on to say:
"Unlike monogenic diseases, including cystic fibrosis
or Duchenne muscular dystrophy, in which case mutation
equals disease-causing, the causes of [other] common
diseases [such as heart disease] are a combination of
environmental factors as well as several genetic factors."