Genes Explored As Key
To Cholesterol Levels

NEW YORK (Reuters Health) - Genetic research on inherited forms of high cholesterol is offering clues to the roots of the elevated cholesterol counts commonly seen in the general population, researchers report.

Scientists are finding that a glitch in the liver's ability to clear fats from the blood is the common thread among the four different types of inherited high cholesterol. This suggests that in the general population, some yet-unidentified genes may impair the liver's cholesterol-clearing capacity, according to a report in the May 18th issue of Science.

LDL cholesterol, the ``bad'' cholesterol linked to heart disease, is significantly elevated in four types of genetic disorders that cause soaring cholesterol and heart disease at a young age. And recent research has shown all four disorders inflict their harm by preventing LDL receptors in the liver from clearing LDL from the blood, write Drs. Joseph L. Goldstein and Michael S. Brown of the University of Texas Southwestern Medical Center in Dallas.

According to the authors, this understanding of how genes affect LDL creates ``a sense of optimism that new and more powerful ways'' of lowering blood cholesterol are on the horizon.

For most people, a diet high in saturated fat and cholesterol is the key culprit behind unhealthy LDL levels. But as with the genetic disorders, liver LDL receptors are also involved; overwhelming the liver with dietary cholesterol causes the receptors to become less active.

``The liver decides, 'I don't want anymore,''' Brown explained in an interview with Reuters Health. ``It defends itself. And then LDL builds up in the blood.''

But while a fatty diet can overburden the liver, Brown said, experts believe that genetic factors determine whether a person is more or less susceptible to these dietary effects.

``Nearly everyone in our society eats a high-cholesterol diet,'' he said, ``but not everyone gets heart disease.''

The search for genes linked to cholesterol levels in the general population is just starting, but the recent successes in research on inherited cholesterol disorders should help, according to Brown.

Just last month, investigators reported in Science that they had discovered the genetic defect linked to one of the disorders, called autosomal recessive hypercholesterolemia. That work and other research, Brown said, has ``exposed a group of genes'' that affect LDL levels, at least for some people.

It may be, he explained, that these same genes are involved in elevated LDL among ``normal'' people. More subtle mutations in these genes, for example, may make healthy people prone to higher cholesterol levels. On the other hand, entirely different genes may be to blame.

Once scientists can pinpoint the responsible genes, Brown said, the goal will be to tailor cholesterol drugs to an individual's genetic make-up.

SOURCE: Science May 18, 2001.

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