The MI doesn't fall far from the family tree

LGALS2 gene plays a crucial role in myocardial infarction risk

By Tony Craig

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 of Nature.

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."