Does anyone else feel that one of life’s singularly unfair phenomena is that some people can live on buttered eggs, dripping bacon and marbled steak yet never show any sign of heart disease? You know—the people who live to 95 and smugly assert that they never so much as met a low-fat food.
A study in today’s issue of the journal Science goes a long way toward solving the mystery, which you can probably guess: some people carry a genetic mutation that defends the heart against the effects of a high-fat diet—specifically, breaking down triglycerides, those fats that clog arteries like hair in your bathroom drain.
The researchers, led by Toni I. Pollin and Alan R. Shuldiner of the University of Maryland School of Medicine, hit on a neat approach: they recruited 809 volunteers from among the Old Order Amish of Lancaster County, Pa. The virtue of this population is that they are pretty genetically homogeneous, compared to a random group of Americans. That means that if a gene has a certain effect, the researchers are more likely to find it. Think of it this way: the effect of any one gene—for, say, levels of an enzyme—depends on all the rest of the genes an individual carries. If some of those “background” genes wash out the effect of the gene of interest, by (say) affecting levels of the same enzyme, then the gene of interest will have different effects in different people, and the study will have a hard time linking it to any particular phenotype. Genetic homogeneity should prevent that complication.
One gene stood out: about 5 percent of the Amish had a mutation in a gene called APOC3. This gene encodes a protein, called apoC-III, that inhibits the breakdown of triglycerides, those nasty fat particles in the blood. People with the mutation produce half the amount of apoC-III that the rest of us do. With only half of the protein that inhibits the breakdown of triglycerides, that breakdown can proceed at warp speed—and the result is fewer triglycerides sloshing around the bloodstream and clogging arteries, including after that high-fat milkshake. The people with the mutation also had high levels of “good” (HDL), low levels of “bad” (LDL) cholesterol and, not surprisingly, less atherosclerosis (hardening of the arteries). In short, they are less likely to develop cardiovascular disease even if they eat all the wrong things.
“Our findings suggest that having a lifelong deficiency of apoC-III helps to protect people from developing cardiovascular disease,” Pollin said.
The practical import of this isn’t that you should rush off to have your genome tested for this mutation so you can safely switch from skim milk to 78-percent-fat milkshakes. For one thing, genetic analysis suggests that the mutation was introduced into the Amish of Lancaster County by someone born in the mid-1700s, which is when the Amish arrived in Pennsylvania from Europe. If you do not trace your ancestry to this group, there’s about zero chance that you have the protective mutation. (Though I can certainly foresee the day when people with other protective mutations will tell dietitians to take their advice, meant for the general population, and shove it).
Instead, Pollin and her colleagues think the discovery may pave the way to drugs that target apoc-III. Just as the mutation causes a body to make less of the protein that inhibits the breakdown of triglycerides, so a drug might also lower levels of apoc-II and make triglycerides sitting ducks for enzymes that tear them apart.