Sausage or Fresh Fruit? It May Not Matter at All to Your Genes

By SHARON BEGLEY | Staff Reporter of THE WALL STREET JOURNAL – 8/23/02

The research of Jose Ordovas is driven by a simple observation: Only some of us take prescription drugs; everyone eats.

Research in “pharmacogenomics” has shown that the reason the same drug helps some patients, has no effect on others and kills an unlucky few reflects not blind chance but individual genetic differences.

Variations in cytochrome P450 genes, for instance, determine whether or not you make the enzyme that breaks down selective serotonin reuptake inhibitors, also know as SSRIs, like Prozac and dozens of other drugs, and so whether a standard dose will harm you. Tiny variations in the beta 2AR gene determine how asthma patients respond to albuterol. And Genaissance Pharmaceuticals of New Haven, Conn., recently discovered 29 genetic variations that affect how you respond to cholesterol-busting statins.

If DNA variations shape how we respond to drugs, reasoned Dr. Ordovas, director of nutrition and genomics at USDA’s Human Nutrition Research Center, Tufts University, Boston, shouldn’t they affect how we respond to food?

Circumstantial evidence says so. One person goes on a low-fat/low-cholesterol diet and sees levels of LDL, or “bad cholesterol,” plunge. Another substitutes trout for T-bone until he swims and still doesn’t see his cholesterol budge. One person can live on marbled beef and butter with no ill effects. Another gets a coronary.

This month, researchers led by biochemist James Ntambi of the University of Wisconsin in Madison report that mice lacking a gene called SCD-1 can eat all the rich, fatty foods they want and never become obese or diabetic. Humans have SCD-1 equivalents, raising the intriguing possibility that absence of these genes explains the lucky few who reach the age of 90 despite living on Big Macs.

The study of how food interacts with genes is called nutrigenomics. Although barely out of the starting gate, it is already explaining some puzzles. For instance, a gene called Apo E comes in three common varieties, or alleles. Apo E4 is associated with a higher risk of cardiovascular disease. But if an Apo E4 person eats a heart-healthy diet (fewer than 30% of calories from fat, fewer than 300 mg of cholesterol a day), he gets much more benefit than do other genotypes, and so faces virtually no increased risk of heart disease despite the “bad” gene.

“Environment is the leverage you have over your genes,” says geneticist Frederic Abramson. “What you can change most easily in your environment is what you eat.”

Only when an Apo E4 person meets a high-fat diet does trouble brew. His lipid and cholesterol levels soar, much more than Apo E2s or 3s do on an identical diet. Those lucky slobs can pack in buttered muffins with near impunity. But things even out: The lipid and cholesterol levels of Apo E2s and 3s respond less to a heart-healthy diet. And if you have mutations in the Apo A4 gene, those levels don’t respond at all to a healthy diet. All that broccoli for nothing.

A drink or two a day also seems to reduce the risk of heart disease, but this one-size-fits-all advice is genomically naive, too. Alcohol dials down cholesterol levels in Apo E2s, but increases it in Apo E4s. Similarly, exercise increases HDL, or “good cholesterol,” in Apo E4s, but has little effect on HDL in 2s and 3s. Still choking on oat bran? It can lower serum cholesterol only in Apo E3s, notes Artemis Simopoulos, president of the Center for Genetics, Nutrition, and Health in Washington. The rest of us needn’t bother.

Also genomically naive is the advice to limit sodium. Only 15% of the population has sodium-sensitive hypertension; for everyone else, cutting sodium has almost no effect on high blood pressure, says Gerald Combs, director of the USDA’s Human Nutrition Research Center in Grand Forks, N.D.

A final example. Women are told to load up on calcium for bone health. But the gene for the Vitamin D receptor has multiple alleles. “Some of the forms this receptor takes don’t respond as well to increased calcium,” says Dr. Simopoulos. With nutrigenomics, she says, “we’ll be able to target dietary advice based on your genome, rather than make general rules that fail for so many people.”

Dr. Abramson founded AlphaGenics in 1999 on that premise. For about $1,000, the Washington, D.C., company plans to offer genetic profiles, based on about 300 genes that predict how an individual will respond to a particular diet.

Standard medical testing is a long way off. But if a pilot test goes well this fall, AlphaGenics hopes to tell you whether choosing oatmeal over sausage will actually make a difference to your health.

E-mail me at sciencejournal@wsj.com.

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