Let me make a prediction about your future. I predict that soon you’ll become interested in a subject that you probably know nothing about right now. Nutrigenomics! What is it? It is the study of the interplay between our genes and our diet. Nutrigenomics will eventually allow you to walk into a physician’s office, have your genetic makeup analyzed, and walk out with a prescription. But that prescription may not come in the form of pills in a bottle. It may be just a list of specific foods to eat and to avoid.
Let’s begin with a concrete example. About one in 15,000 children is born with an inability to process phenylalanine, a common amino acid found in the diet. The gene that normally gives the instructions for making phenylalanine hydroxylase, the enzyme needed to metabolize phenylalanine, does not function properly. The result is phenylketonurea (PKU), a condition characterized by an accumulation of phenylalanine in the brain, possibly leading to brain damage. Treatment is simple enough. Foods that are high in phenylalanine must be avoided. So here we have a clear example of a link between genetics and nutrition. A genetic aberration sets up the possibility of a disease, but the disease only appears when certain foods are part of the diet.
Luckily, PKU is a rare condition. But heart disease is not. Here, too, both genetics and diet play a role. When a physician takes a medical history and asks about heart disease in the family, he is really performing a primitive genetic test. If the answer is yes, he will likely recommend a more stringent cholesterol-lowering diet than he would in the absence of such a family history. Of course, we know that not everyone benefits from such a diet. There are numerous cases of people who eschew fat, disdain eggs, and exercise religiously, only to suffer a heart attack. Indeed, about half the people who have heart attacks have normal blood cholesterol levels. However, as we learn more about the actions of genes in our body, we will be able to identify those who are likely to benefit from specific dietary recommendations. Like those people who carry a variant of a gene that codes for a protein with the tongue-twisting name of Apolipoprotein E.
Cholesterol is not an evil molecule, although it is clearly associated with heart disease. Actually, every cell in our body requires it. Cholesterol is both part of the cell membrane, and also the raw material cells use to manufacture sex hormones, bile acids, and a variety of essential biochemicals. But we do not need to consume cholesterol in our diet; the liver is capable of making it. Since cholesterol is not soluble in blood, it has to be transported around by attaching to molecules called lipoproteins. One of these is Apolipoprotein E. Like any protein in the body, it is made when the gene that “codes” for it is turned on. Unfortunately, though, there are several different forms, or “alleles,” of this gene. One variant gives rise to a form of Apo E that deposits excessive cholesterol in the coronary arteries, where it can cause the buildup of plaque and lead to hardening of the arteries.
Finland has one of the highest rates of heart disease in the world, and also has one of the highest frequencies of the variant Apo E gene in its population. Japan has a low rate of heart disease, and the variant Apo E is rarely found in Japanese. However, the presence of the gene is not enough to explain the disparity in heart disease rates! The Finns may have a greater genetic susceptibility, but it is their high-fat diet that converts the susceptibility to active disease. In other words, a Finn who knew that he had this genetic variant would do well to pay very close attention to diet. The Apo E variant may be there, but it is less likely to cause damage if there is less cholesterol available to deposit.
The natives of Papua New Guinea present an interesting example. Here, for some reason, the frequency of the variant Apo E gene is extremely high, and one would expect the incidence of heart disease to be high as well. But it isn’t. At least it hasn’t been—until recently. That’s because the diet, perhaps aside from the occasional plump missionary, has been extremely low in fat. Now, with a Western lifestyle encroaching, heart attacks at a young age are becoming common. Genes may deal you a poor hand, but lifestyle can still be an ace in the hole.
Of course, many genes—not just one—play a role in heart disease. Virtually every newspaper picked up a report from the New England Journal of Medicine that described the case of an eighty-eight-year-old gentleman who, for at least fifteen years, ate twenty-five soft-boiled eggs every day and still maintained a normal blood cholesterol level! He had a genetic variation that prevented cholesterol absorption from the gut. Wouldn’t you like to know if you had such a genetic gift?
Heart disease is not the only condition that links genes and diet. There is evidence that autism, and even schizophrenia, may have such connections as well. A flaw in the production of an intestinal enzyme may lead to milk proteins not being completely degraded into amino acids in the gut, and result in the absorption of amino acid aggregates, which may have adverse effects on the brain. Then there is cancer. In some cases, a gene that codes for an enzyme, known as cyclooxygenase-2, is overactive and can lead to malignancy. However, resveratrol in grapes and curcumin in turmeric have been shown to inhibit the activity of this gene. So in the future, once your doctor has looked at your genetic profile, you may be told to drink grape juice and eat curry to reduce your personal risk of colon cancer. And how will the doctor do the genetic test? Believe it or not, a palm-sized instrument capable of analyzing your DNA is around the corner. Nutrigenomics, here we come!