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Studies Highlight New Cholesterol Findings

Gene linked to the substance; levels found to vary with the seasons

MONDAY, April 26, 2004 (HealthDayNews) -- New experiments in mice have uncovered a gene that can increase cholesterol levels.

And a second study has confirmed that your cholesterol reading can change with the seasons.

In the first study, a newly discovered gene was found to play a large role in the levels of low-density lipoprotein (LDL) cholesterol, a fatty molecule that contributes to hardening of the arteries.

Kara Maxwell, an M.D.-Ph.D. student at Rockefeller University in New York City, and her colleague, Dr. Jan L. Breslow, found that a gene called Pcsk9 reduces the number of receptors on liver cells that remove LDL cholesterol from the blood.

"It appears that when you have too much of Pcsk9, it causes decreased LDL receptor protein and function," Maxwell said. "This leads to high levels of LDL cholesterol in the blood."

Maxwell and Breslow fed one group of mice normal diets and another group high-cholesterol diets. They then examined the gene activity in the mice and found a previously unknown gene.

This gene was seen at much lower levels among mice on the high-cholesterol diet, compared with mice fed normal the diet.

To find out what the gene did, the researchers inserted the gene into normal mice, where it made high levels of Pcsk9 protein inside liver cells. The mice developed five times the normal level of LDL cholesterol.

Maxwell was able to confirm this finding in other experiments, according to her report in this week's issue of the Proceedings of the National Academy of Sciences.

"It is not yet clear how this gene works in humans," Maxwell said. "But we hope the mouse study will help us understand how the gene works in humans."

Maxwell believes this gene could one day be a drug target to reduce LDL cholesterol. "Much more work needs to be done before you could take these findings and make a drug target," she added.

Dr. Ron Krauss, director of atherosclerosis research at Children's Hospital Oakland Research Institute and a spokesman for the American Heart Association, said that "lowering LDL cholesterol is an important target for reducing heart disease risk."

Krauss thinks a drug targeted at this gene combined with current treatment might be able to lower cholesterol even more. It may also be useful for patients who experience side effects from current cholesterol medications.

But since the exact beneficial level of the Pcsk9 protein is not yet known, "it is hard to imagine how this finding will be translated into something that is clinically useful," Krauss added.

In the second study, a research team led by Dr. Ira S. Ockene, a professor of preventive cardiology at the University of Massachusetts Medical Center, confirmed earlier research that had shown cholesterol levels vary with the seasons, reaching highest levels during the winter.

"There is seasonal variation in the level of cholesterol," Ockene said. "But the level of variation is smaller than had been previously reported."

The level of change was greater in women than in men, and it was also greater in people with higher levels of cholesterol, Ockene noted.

Ockene and his colleagues collected data on 517 healthy volunteers. For 12 months, the scientists recorded diet, physical activity, exposure to light, general behavioral information and cholesterol levels, according to their report in the April 26 issue of the Archives of Internal Medicine.

The researchers found the average cholesterol level in men was 222 milligrams per deciliter (mg/dL) of blood and 213 mg/dL in women.

The level considered the start of high cholesterol is 240 mg/dL, according to the U.S. National Cholesterol Education Program guidelines.

Over the year, men's cholesterol levels increased by 3.9 mg/dL, peaking in December, and women's increased by 5.4 mg/dL, peaking in January. In addition, these increases were greater in those who had high cholesterol levels in the beginning.

These changes were not explained by diet or weight change, Ockene said. He suggested that since blood volume increases in the summer and decreases in the winter, cholesterol is diluted during the summer and more concentrated in the winter.

Based on these findings, Ockene said doctors need to measure cholesterol at different times during the year to get an accurate reading and determine the effectiveness of cholesterol treatment.

Ockene noted there "are tides in our lives, big seasonal changes that affect us in many ways," and this seasonal variation in cholesterol levels is just one of those.

Dr. Russell V. Luepker, the Mayo Professor of Epidemiology at the University of Minnesota, said this finding is interesting and it's something his research team has reported before.

"The differences aren't great enough to change the standards for diagnosis or treatment," Luepker said. "We all have cycles we go through, and seasons affect these cycles just as day and night affects them."

More information

The National Heart, Lung, and Blood Institute can tell you about cholesterol and the risk of heart attack. The American Heart Association can tell you more about cholesterol.

SOURCES: Kara Maxwell, M.D.-Ph.D. student, Rockefeller University, New York City; Ira S. Ockene, M.D., professor, preventive cardiology, University of Massachusetts Medical Center, Worcester; Russell V. Luepker, M.D., Mayo Professor of Epidemiology, University of Minnesota, Minneapolis; Ron Krauss, M.D., director, atherosclerosis research, Children's Hospital Oakland Research Institute, Calif., and spokesman, American Heart Association; April 26, 2004, Archives of Internal Medicine; April 26-30, 2004, Proceedings of the National Academy of Sciences
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