WINSTON-SALEM, N.C. -- Physicians at Wake Forest University Baptist Medical Center reported today the first demonstration of a gene-diet interaction that affects the absorption of cholesterol in humans.
Richard B. Weinberg, M.D., professor of internal medicine and head of the section on gastroenterology reported at the American Heart Association meeting that the demonstration could eventually pave the way for individualized diet prescriptions.
For several years, Weinberg has been studying a common genetic variant of a standard protein in the blood that appears to protect the people who have it from excess dietary cholesterol.
In the current study, Weinberg and his colleagues reported, "The amount of cholesterol our subjects absorbed was controlled by the type of fat in the diet and whether or not they carried the variant gene. Subjects with the apo A-IV-2 (the scientific name for the variant gene) absorbed much less cholesterol than the 'normal' subjects."
He said about 15 percent of the population carry the apo A-IV-2 gene; most of the rest have the apo-A-IV-1 gene. In the current study, the subjects, mostly medical students and staff members of the Wake Forest University Baptist Medical Center, were tested with three high cholesterol diets, varying the amounts of saturated fat or polyunstaurated fat.
The investigators compared people with the normal gene to people with the variant gene on each of the three diets.
One diet had 35 percent of the daily calories from fat, and 15 percent of total calories were from saturated fat. The second diet also had 35 percent of the calories from fat, and 15 percent of total calories from polyunsaturated fat. The third high-cholesterol diet was low fat, with only 20 percent of the calories from fat, and the fat was made up of equal amounts of saturated fat, polyunsaturated fat (such as vegetable oil) and monounsaturated fat (such as olive oil).
On the diet where the fat came from polyunsaturated fat, the amount of cholesterol absorbed jumped substantially in the "normal" group, while remaining virtually unchanged in the group with the variant gene. The difference was statistically significant.
Absorption of cholesterol was lowest on the low fat diet, but the difference between the gene groups was not significant. On the high saturated fat diet, both gene groups absorbed more cholesterol, but again the difference was not significant.
"Studies such as this represent the first wave of applying knowledge of the human genome to the study of how diet can prevent chronic diseases," Weinberg said
The study was conducted in the General Clinical Research Center under one of the initial nutrition initiative grants of the Center for Research on Human Nutrition and Chronic Disease Prevention.
In one earlier study, published in the New England Journal of Medicine, Weinberg and two residents had tried a four-egg-a-day diet on 23 medical students. They compared 11 medical students with the variant gene to 12 who had the more common gene. In the normal students on the four-egg diet, cholesterol increased 22 points in three weeks, a low density lipoprotein (LDL, the bad cholesterol), increased by 19 points. In contrast, cholesterol increased by only 5 points, and LDL by only 2 points in students with the variant gene.
Weinberg said the variant gene affects dietary responsiveness by altering the efficiency of intestinal absorption of cholesterol.
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