Study Downgrades Gene as Heart Risk Factor

TUESDAY Sept. 18, 2007 -- Variations in the apolipoprotein (APO) gene are not as important an indicator of coronary risk as has been thought, according to a new British analysis of previously published studies.

The APO gene comes in three varieties -- E2, E3 and E4. All forms of the gene produce a protein that is an important component of the fat and protein complexes found in blood plasma, and that plays an important role in the metabolism of cholesterol and the fats called triglycerides.

Some previous studies have found an association between specific APOE versions -- generally E2 -- and lipid levels, according to the report, published in the Sept. 19 issue of the Journal of the American Medical Association by a group led by John Danesh of the University of Cambridge.

But many of those studies were too small to be reliable, said study co-author Dr. Emanuele Di Angelantonio. A meta-analysis that assessed 82 studies of blood fat levels and 121 studies of coronary outcome showed that the association with APO E variants showed that the links were not as strong as once suspected, he said.

"People with APO E2 have a 20 percent lower risk of coronary disease," Di Angelantonio said. That was about twice as weak as had been previously reported, the journal report said. Coronary risk was increased slightly for carriers of the APO E4 variant.

There has been talk about screening for APO E variants to help determine coronary risk, but "it is almost impossible to use APO E for screening," Di Angelantonio said. "APO E2 is a relatively rare mutation."

Which is just as well, said Dr. Daniel J. Rader, director of preventive cardiology at the University of Pennsylvania, since APO E variants can affect the risk of other conditions. Specifically, APO E4 has been linked to an increased risk of Alzheimer's disease, Rader noted.

"I actually did APO screening for a while," he said. "I found myself in the awkward position of having to explain what APO E4 means in terms of Alzheimer's disease."

The new meta-analysis does confirm "what we've known for some time, that APO E is one of the more important genes that determine the risk of heart disease," Rader said. "But it is a great example of why we need federal legislation in terms of protecting people in genetic screening programs."

Positive steps can be taken to reduce the risk of coronary disease for those carrying a gene that increases the risk, Rader said. "But for Alzheimer's, we can do nothing. If you carry E4, you might be subject to discrimination."

Such a screening program involving APO E is highly unlikely now, Di Angelantonio said. "It is too early to speak about assessing coronary risk with genotypes, and this study demonstrates that," he said.

More information

More on heredity as a risk factor for heart disease is provided by the American Heart Association.

Posted: September 2007


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