Scientists have moved closer to understanding why some individuals seem to get away with eating high-cholesterol foods without absorbing any more cholesterol than other, more health-conscience people.

Researchers from UT Southwestern and the National Institutes of Health (NIH) recently made a discovery that narrowed the search for a gene responsible for abnormal, cholesterol absorption in individuals with a rare hereditary disease. While cholesterol metabolism has been well-documented, scientists understand little about how cholesterol is absorbed from our diet and excreted by the body.

"Only a fraction of the cholesterol we consume is actually absorbed by the body," said Dr. Shailendra Patel, a scholar in the Center for Human Nutrition and assistant professor of clinical nutrition at UT Southwestern. "Different people absorb different amounts. Some might eat a cholesterol-laden meal and absorb 30 percent of it; someone else might eat a low-cholesterol
meal but absorb 60 percent of it."

The researchers studied 10 families with sistosterolemia, a rare, recessively inherited disease characterized by the accumulation of plant sterols, premature heart disease and fatty deposits on the skin and tendons. Plant sterol is akin to cholesterol in animal products but normally is not absorbed by the body.

"In normal individuals, the body has the ability to selectively absorb cholesterol and exclude plant sterols," said Dr. Patel, lead author of the study published in the Journal of Clinical Investigation. "Individuals with sistosterolemia hyperabsorb cholesterol but also absorb plant and shellfish sterols that are not normally absorbed. Hence, the gene that is disrupted may regulate selective absorption of dietary cholesterol.

"If we want to change someone's cholesterol absorption, this gene would be the target of treatment," Dr. Patel said. "We hope this is the key gene that will allow us to target cholesterol absorption as a whole new form of drug therapy." "Our studies of sitosterolemia may help explain the mechanisms responsible for cholesterol uptake from the diet and on mechanisms that protect us from absorbing and retaining substances in food that are potentially harmful, "said co-author Dr. Michael Brownstein, chief of the NIH's Section on Genetics.

The researchers examined the genes of families from India, Finland, the Netherlands, Japan and the United States and mapped the genetic defect to chromosome 2p21. Others participating in the study included Dr. Scott Grundy, director of the Center for Human Nutrition; Mi-Hye Lee, a fellow in the nutrition center; Dr. Gerald Salen of UMDNJ-New Jersey Medical School; and scientists from Shiga University of Medical Science (Japan), Johns Hopkins Hospital, University Hospital Jijmegen (The Netherlands) and University Hospital of Helsinki (Finland).

The study was supported in part by grants from the Department of Veterans Affairs, U.S. Public Health Service, Ministry of Education (Japan), American Heart Association, Southwestern Medical Foundation and the Moss Heart Foundation.