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Arteries clogged? Blame yuor genes

You don't smoke, you exercise regularly, count every gram of fat and are ever-vigilant of your cholesterol, yet your arteries remain full of the low-density lipoproteins that can lead to obstructions.

Blame it on your genes.Scientists are building a strong case that genetic variations influence how the human body processes foods, particularly fats, predisposing some people to have high "bad" cholesterol levels and be at higher risk for heart attack or stroke, as well as to obesity.

But as researchers gain better understanding of how gene variations affect response to diet, it may be possible to make more sophisticated adjustments to compensate, experts said during the annual meeting of the American Association for the Advancement of Science, which ended Tuesday.

"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. That's our hope. That's our dream," said Dr. Ronald Krauss, head of the Molecular Medicine Department at the Lawrence Berkley National Laboratory, University of California, Berkeley.

Most of what has been done in heart disease and blood pressure prevention treatment in the past few decades has been based on population studies that averaged out how a large number of people responded to a change in diet or other liffestyle change, like reducing salt intake to lower blood pressure.

"We know that individual responses to food cannot be reliably predicted on the basis of these studies," Krauss said.

Krauss said recent research on LDL cholesterol has found two different patterns, A and B, that seem to be geneticlaly influenced. The B pattern is characterized by small, dense particles of LDL, lower blood levels of the "good" HDL type of cholesterol, increased blood levels of triglycerides and a predisposition to the most common form of diabetes. By contrast, pattern A features larger LDL particles.

"Each of the features in Pattern B confers increased risk of heart disease, resulting in an overall three-fold higher risk compared with individuals with larger LDL," Krauss said. Pattern B is found in about one in three adult men and one in five or six post-menopausal women.

He added that his research has shown "efforts to reduce incidence of heart disease by modifying fat intake may be much more effective in high risk Pattern B individuals than in Pattern A subjects."

Dr. Jan Breslow is a senior scientist at the lab for bichemical genetics and metabolism at Rockefeller University who has been devloping genetically altered mice to study heart disease. He said that "at this point we don't know how many genes might influence the arteries, but it's more than one. It might be five, 10 or 100.

Mice don't ordinarily get arterial disease, but when genes are mutated so that they make less of a cholesterol-clearing substance in their blood, they develop lesions that can become clots resembling those in humans. And if the mice are fed high-cholesterol, high-fat, Western style diets, they develop the lesions even faster.

And Dr. Claude Bouchard, an obesity researcher at Laval University in Quebec who has done extensive work on the metabolism of identical twins, said he believes that 50 to 70 percent of all people suffering from high cholesterol are genetically influenced, while between 20 and 40 percent of obesity is genetically programmed.

His study involved 12 pairs of young adult male twins who were overfed by about 1,000 calories a day for 100 days. The twin brothers, who were kept inactive, were all very much like each other in weight and body fat gain and blood cholesterol changes and were also largely in tandem when it came to shedding the 4 to 6 pounds each had gained.