MUSC may help develop new drug

TARGETING CHOLESTEROL: A team of doctors that found the cholesterol gene is conferring with a biotech company. Staff Photo by Brad Nettles- Drs. Mi-Hye Lee (front, from left), Shailesh Patel and Starr Hazard search for abnormalities in a DNA sequence at MUSC’s endocrinology lab Tuesday. Looking on from the lab table is Dr. Kangmo Lu. These doctors have discovered the gene that regulates cholesterol absorption. (384308) Imagine eating a well-marbled steak, french fries, an avocado salad with blue cheese dressing and a croissant with lots of butter – without instant cholesterol overload.

Pop a pill and the cholesterol would flow out of the body instead of building up and causing cardiovascular disease, America’s No. 1 killer.

A dream for now, but one that researchers say may be possible, eventually.

A Charleston doctor discovered a gene that helps to regulate how much cholesterol the body absorbs, and it could lead to a new type of cholesterol-lowering medicine.

Dr. Shailesh Patel and three colleagues at the Medical University of South Carolina are studying the gene and collaborating with a biotech company to develop a drug.

It probably will take eight to 10 years for a medicine to reach the market, but finding the gene starts the process, said Patel, endocrinologist and assistant professor of medicine.

About half of adult Americans have cholesterol levels higher than the desirable 200 or less, Patel said.

South Carolina ranks at the top nationwide in cardiovascular disease occurrence and death rates, and residents eat a diet high in saturated fat, the fat that affects how much cholesterol a person makes and absorbs, Patel said.

The gene that Patel identified, ABCG5, regulates the cholesterol absorption rate. People normally absorb 45 to 55 percent of the cholesterol in their diet and excrete the rest, Patel said.

“You can’t burn cholesterol,” he said. Bile acids absorb cholesterol so it can be excreted, and a smaller amount is directly excreted into the bile, he said.

Patel found the gene by studying individuals and families who have a very rare disease called sitosterolemia.

People with one copy of the gene ABCG5 may have heart attacks in their 30s while people with two copies of the gene (actually either of two genes next to each other on the DNA chain) can have heart attacks as early as age 10, he said. The gene search and discovery are outlined in this month’s “Nature Genetics” in an article by Patel and an international group of researchers including his MUSC colleagues, Drs. Mi-Hye Lee, Kangmo Lu and Star Hazard.

Patel has found the gene in Americans, Amish, Mennonites, Japanese, French, Dutch, Swedish, South African and other peoples, suggesting it is not tied to any ethnic group, he said.

He also checked the records of children with heart disease, found the gene, contacted the patients’ doctors and explained treatments.

“We have lost no one. They all are still alive although some have had (heart) bypasses,” Patel said.

If a doctor doesn’t know about the gene, however, the cholesterol absorption problem isn’t treated, he pointed out.

Patel expects to seek volunteers for a genetics study, based on blood samples, to see if he can predict cholesterol absorption based on genes.

In a couple of years, he hopes to know whether a genetic test will be worthwhile.

Drugs called resins (such as Questran and Colestid) help rid the body of cholesterol but cause difficult side effects. Statin drugs (such as Lipitor and Zocor) inhibit the liver from making cholesterol but don’t help the body shed it, Patel said. The two types combined are very powerful, he added.

A future drug, based on the ABCG5 gene, hopefully would help people who have heart disease and high cholesterol, whether it’s caused by genetics or diet, Patel said.

The gene and the protein it makes might explain why some people respond to a cholesterol-lowering diet while others lose weight without seeing their cholesterol drop much if at all.

Meanwhile, South Carolina residents need to be aggressive in treating high cholesterol as well as the obesity, high blood pressure and diabetes that are so common here and that contribute to cardiovascular disease, said Patel.

“Cut back on saturated fat,” he advised. “Saturated fat affects how much cholesterol you make and absorb in your body. Saturated fat is the killer.”

Saturated fats are found in meat, butter, lard and other fats that remain solid at room temperature, peanut and coconut oils, nuts and avocados, Patel said.

Olive oil, safflower and corn oil are good alternatives as is margarine made from those oils, he said.

Foods stating “contains no cholesterol” may be loaded with saturated fat, cause weight gain and drive up cholesterol, Patel said.