Study finds genetic link to high cholesterol

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Study finds genetic link to high cholesterol

By Suzanne Rostler

NEW YORK, Apr 12 (Reuters Health) - Patients with a disorder that places

them at high risk of premature heart disease may have a gene that causes

them to overproduce a cholesterol-carrying molecule, researchers suggest.

While the new research does not implicate a particular gene responsible for

production of the substance, known as apolipoprotein B (apoB), the findings

could pave the way for finding such a gene, or genes.

This could in turn lead to the development of new treatments to reduce heart

disease risk, Dr. Q. Purnell of Oregon Health Sciences University

in Portland said in a statement.

Patients with the disorder, known as familial combined hyperlipidemia

(FCHL), have metabolic defects that cause them to have very high fat levels

in their blood. They also tend to be insulin resistant, meaning their bodies

are less sensitive to the effects of this hormone, which is needed for

normal sugar metabolism. About 1 in 10 Americans with premature heart

disease have FCHL, and roughly 1 in 100 Americans overall have FCHL.

Purnell and colleagues tested whether insulin resistance and increased

levels of apoB were related in people with FCHL. They also investigated

whether having an accumulation of fat in the abdomen--which, for people in

the general population, increases the risk of insulin resistance--played a

role in insulin resistance in people with FCHL.

The investigators found that while abdominal fat and insulin resistance did

indeed contribute to elevated apoB levels in FCHL patients, these factors

alone were not enough to account for the increase. Genes, they conclude in

the April 13th issue of Arteriosclerosis, Thrombosis and Vascular Biology:

Journal of the American Heart Association, may also play a role.

Purnell's team compared levels of apoB, total cholesterol and triglycerides,

and measured insulin resistance and abdominal fat in three groups of people.

The first group included 11 patients with FCHL, the second group included 11

people without the disorder matched for age, and the third group included 11

healthy people matched with patients for both age and weight.

Not surprisingly, individuals with the genetic disorder had significantly

higher levels of apoB, total cholesterol, triglycerides, LDL ( " bad " )

cholesterol, and another type of fat known as very-low density lipoprotein

(VLDL) than people in the other groups. But levels of apoB were higher in

patients with FCHL even when the degree of insulin resistance and amount of

abdominal fat were equal.

And while insulin resistance was found to correlate with abdominal fat, it

was not related to apoB levels among patients. Similarly, abdominal fat was

not associated with increased levels of apoB.

" We found that central obesity and insulin resistance cannot fully account

for the elevated lipid levels and that some other process is occurring that

further increases secretion of triglyceride and cholesterol-rich particles, "

Purnell told Reuters Health.

These results, the authors write, suggest that there may be a genetic

component to FCHL that controls the production of apoB.

" These data provide support for genetic models describing a major, but

separate, gene(s) for elevated apoB distinct from genes with effects on

triglyceride and small dense LDL in subjects with FCHL, " the authors

conclude.

Purnell said that his team is currently investigating the gene or genes that

may cause the further elevation of apoB and lipid levels in patients.

SOURCE: Arteriosclerosis, Thrombosis and Vascular Biology 2001;21.