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. Jonathan 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.

　　By Suzanne Rostler
　　From Reutershealth