Genetic Involvement in Heart Disease - I

If you watch television at all, you have seen numerous advertisements for various pharmaceuticals. One group of particular importance are drugs designed to lower cholesterol levels, but have you ever wondered what is cholesterol, where does it come from, and how do these drugs act to reduce cholesterol levels?

Cholesterol is a lipid that is an essential component in animal cell membranes. It is produced naturally by the liver but also comes from our diet, specifically from animal foods. Cholesterol and other lipids are essential in that they build hormones, act as cellular messengers, and are a source of energy for the body.

Cholesterol travels through blood plasma in the form of particles composed of cholesterol plus protein. One form of particle is called low-density lipoprotein (LDL) and is associated with atherosclerosis or the narrowing of coronary arteries due to cholesterol deposits called “plaques”. High-density lipoproteins (HDL) or “good cholesterol” serves to reduce plaque formation. Elevated cholesterol levels are associated with coronary artery disease but interestingly, significantly reduced levels of cholesterol can negatively affect the normal growth and development of an individual.

Risk factors associated with cardiovascular disease include smoking, obesity, hypertension, increased cholesterol levels, and positive family history (usually having one or more affected first degree relatives). An individual with a positive family history is 2 to 7 times more likely to have heart disease than one with no family history. This risk range can increase with more affected family members and an early age of onset of the disease.

What role do genes play in familial heart disease? There are more than a dozen identified genes known to contribute but one that has played a key role in our understanding is the LDL receptor gene located on chromosome 19. This gene was cloned in 1984 and has led to significant understanding of cellular mechanisms like endocytosis, which is the process of engulfing particles into the cell, and receptor activity. More than 600 mutations of this gene are recognized. Understanding these mutations and other cellular processes provides critical information on how cholesterol levels are regulated both within the cell and in the plasma.

Next time, we will review a dominantly inherited heart disease called familial hypercholesterolemia (FH). FH is one of the most common autosomal dominant disorders, accounting for approximately 5% of myocardial infarctions (heart attacks) in individuals under the age of 60.