Not Just What You Eat That Affects Risk For Heart Disease And Stroke; Your Genes Influence How Much Damage High-Fat Diet Causes

February 14, 1998

While you can control how much saturated fat and cholesterol you eat in foods, you can't yet control whether your genetic inheritance will turn these fats against you or will confer some protection from them.

Recent research findings, to be presented today at a symposium at the American Association for the Advancement of Sciences (AAAS)'s annual meeting, will highlight the strong influence that genes play in determining individual variations in response to diet. As a result of their actions, these genes can influence whether an individual is predisposed to obesity or to developing atherosclerosis, the disease process that underlies heart disease and stroke, the nation's No. 1 killer.

Such research may help explain why two people who eat the same foods can have very different blood levels of cholesterol, particularly "bad" LDL cholesterol.

High blood cholesterol and in particular high LDL is one of the risk factors for heart disease, according to the American Heart Association, co-sponsor of the AAAS symposium titled, "Gene-Diet Interactions in Coronary Heart Disease." The LDL (low-density lipoprotein) sticks to the inside lining of blood vessels, helping to create the plaque obstructions that block blood flow, causing heart attacks and strokes.

"When a large group of people go on the same diet low in saturated fat and cholesterol, their LDL levels can vary widely," said Ronald Krauss, M.D., organizer of and one of the speakers at the AAAS symposium.

Also speaking at the symposium will be three other internationally recognized scientists in research on genetics and nutrition in cardiovascular disease: Claude Bouchard, M.D., Jan L. Breslow, M.D., and Rene Malinow, M.D.

"Recent evidence indicates that genetic factors can contribute to these differences in dietary response," said Krauss, who is also chairman of the American Heart Association's national volunteer nutrition committee.

Research on the interaction of genes and diet also may help explain the often puzzling differences in dietary response that may occur between two similar individuals who eat the same foods. One individual may be slender and another may be overweight and find losing weight a challenge. One person may have dangerously high blood levels of cholesterol and severe atherosclerosis. The other individual may have low blood levels of homocysteine, the topic of Malinow's talk at the symposium. Recent research suggests that homocysteine may be a new marker for heart disease and stroke risk.

"We now know that individual responses to food cannot be reliably predicted on the basis of studies of large populations of people," said Dr. Krauss. Population studies provide an average, for example, of the effect on blood pressure of reducing salt in food, but not how a specific individual will respond to salt restriction. Medical treatments - such as cholesterol-lowering drugs - are also based on such population studies.

Results of research on the interaction of genes and diet may lead to diet plans and possibly drug regimens tailored to an individual's genetic predisposition for heart disease and stroke, said Dr. Krauss, senior scientist and head of the Molecular Medicine Department at the Lawrence Berkeley National Laboratory, University of California, Berkeley.

"That's our hope, that's our dream," he said, adding that it can be reached by research that will enable easy and effective genetic analysis of individuals.

"As new tools become available for genetic analysis, health professionals may be able to recommend dietary practices that are more appropriate and individualized for heart disease and stroke prevention," explained Dr. Krauss.

At the symposium, Krauss will speak on, "Genetic Factors Influencing Cholesterol Response to Diet." Among his topics will be the apoE4 variant of the apoprotein E, the most well-defined genetic trait affecting LDL response to diet. "People with apoE4 have a tendency for higher blood cholesterol levels, increased heart disease risk, and increased risk for Alzheimer's disease," he said.

Krauss also will describe recent research on the LDL subclass pattern B, characterized by "small, dense" forms of LDL, lower blood levels of the "protective" HDL form of cholesterol, increased blood levels of triglyceride and a predisposition to the most common form of diabetes mellitus. This common, genetically influenced condition influences the blood cholesterol response to a low fat diet. "This trait is found in about one in three adult men and one in five to six postmenopausal women," he said.

"Each of these features confers increased risk of coronary heart disease, resulting in an overall three-fold higher risk compared with individuals with larger LDL," he explained. Larger LDL is called pattern A. His research has shown that "efforts to reduce the incidence of heart disease by modifying fat intake may be much more effective in high-risk pattern B individuals than in pattern A subjects who have a normal blood cholesterol profile."

Research findings showing that dietary fat-induced changes in LDL particle size and density phenotypes are linked to candidate genetic loci also will be described by Dr. Krauss.

"Genetic factors can predispose people to obesity," said Bouchard, a scientist and Donald B. Brown Chair on Obesity at the department of preventive medicine at Laval University in Quebec, Canada, who will speak about, "Genetics of Obesity and of the Response to Overfeeding."

"When pairs of identical twins were overfed by the same amount of calories, we noted that brothers of the same pairs were very much alike in weight and body fat gain and in blood cholesterol changes.

"In contrast, we observed large differences between members of different twin pairs," he added. "On the basis of these observations and of research conducted on the panel of families from the Quebec Family Study, we conclude that there are individuals genetically at risk of becoming overweight and obese.

"Similarly, when exposed to a caloric surplus for long periods of time, there are individuals who are at greater risk of experiencing detrimental alterations in the regulation of their blood cholesterol levels," he said.

Breslow, senior scientist at the laboratory of biochemical genetics and metabolism and Frederick Henry Leonhardt Professor at Rockefeller University, New York, will speak about, "Induced Mutant Mouse Models of Lipoprotein Disorders and Atherosclerosis."

"As a species, the mouse is highly resistant to atherosclerosis," said Breslow. "Through induced genetic mutations, it has been possible to develop lines of mice that are susceptible to this disease. For example, mice that are deficient in apoliprotein E (ApoE), an organizing molecule important to lipoprotein clearance from the blood, develop atherosclerotic lesions resembling those that occur in humans." These lesions are worse when the mice are fed a high-cholesterol, high-fat, Western type diet.

"These mice now give us a good animal model to test the effects of diet constituents, such as monounsaturated fats, trans fatty acids, fish oils, and vitamins, not only on the lipoprotein profile but on atherosclerosis itself," Breslow added.

"Genes, Vitamins, Homocyst(e)ine and Cardiovascular Diseases" will be the symposium topic of Malinow, a scientist at the Oregon Regional Primate Research Center, Beaverton, and professor of medicine at Oregon Health Sciences University, Portland.

High blood levels of the amino acid homocysteine, a natural byproduct of the metabolism of food, have been associated with increased risk for heart disease, stroke and atherosclerosis in blood vessels of the limbs.

"Thus, blood homocysteine may be a risk factor for atherosclerosis in a similar fashion as smoking, high blood pressure and high cholesterol levels," he said. Indeed, due to scientists' increasing attention on homocysteine, this amino acid may be "the cholesterol of the next century," he said.

Insufficient intake of folic acid or vitamin B-6 has been cited as one of the causes of high blood levels of homocysteine.

"Many scientists have demonstrated that folic acid supplementation lowers homocysteine levels in most individuals, sometimes requiring additional supplementation of vitamins B-6 and B-12," said Malinow. "We have demonstrated that the decrease of blood homocysteine by folic acid supplementation depends in part on the individual's genetic background."

Note to reporters: fact sheets about each of the four presentations are available. Contact: American Heart Association News Media Relations at 214-706-1340.
-end-


American Heart Association

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