Eating According to Your Genome

Emily Singer
Technology Review

If you knew that you were especially susceptible to heart disease when you gained weight, would it increase your motivation to diet? How much would you be willing to pay to find out if you are one of the lucky people who can eat as much fat as you want and not have an increased risk of heart disease? Such tests are the goal of nutrigenomics, which seeks to identify the links between nutrition and disease based on an individual's genome.

While the field is still too young to offer personal dietary advice for the average consumer, research has uncovered links among genes, diet, and heart disease. Jose Ordovas, director of the Nutrition and Genomics Laboratory at Tufts University, has spent years studying the link between metabolism of dietary fats and risk of cardiovascular disease. After analyzing data from the Framingham Heart Study, a large-scale study that has traced the health of some 5,000 people since 1948, his team has found that certain genetic variants can protect people from diet-induced cardiovascular disease--or put them at increased risk. Ordovas spoke with Technology Review about his research and the future of the field.

TR: Why is nutrigenomics important?

JO: Everybody knows that some people can smoke and live a long life or eat little and still gain weight. But we don't know in advance who these people are. If we did know, these people could be educated to try to avoid the health concerns that could hit later in life. [Nutrigenomics] offers the potential to understand the relationship between food and our health on an individual level.

TR: You have found a striking link between genetic variations in a gene known as apolipoprotein E, or APOE, and risk factors for heart disease, but only under certain dietary conditions.

JO: People with a certain variation, known as APOE e4, are born with a predisposition to heart disease. For these people, a high-fat diet, smoking, or a high BMI [body-mass index] is very bad. For example, they have higher blood glucose levels, a risk factor for heart disease, but only if they have a body-mass index over 30, which is considered obese.

But these people also respond much better to a low-fat, low-cholesterol diet. So they are the ones who should really follow dietary guidelines. If you want to select people for behavior modification, these are the people to start with.

TR: Can people get tested for their APOE variant?

JO: That's a tricky situation. If you have the APOE e4 variant, you're at increased risk for heart disease, which you can do something about. But you also have a higher risk for dementia, which we don't know if you can do anything about. So there are legal and ethical issues associated with testing.

TR: One of the current nutrition debates is over the benefits of omega-3 fatty acids--different studies have produced conflicting results regarding omega-3's ability to protect against heart disease. Can nutrigenomics help sort this out?

JO: We have found that some people are more susceptible to the negative effects of omega-6 [a related fatty acid] than others. Those with a certain variant in the apolipoprotein A, or APOA, gene show a rise in triglycerides, a risk factor for cardiovascular disease, when they eat a diet high in omega-6. In these cases, the protective effect of omega-3 may be overwhelmed by overconsumption of omega-6.

This allele is much more common in Asia, and those who have it are more susceptible to the effect of omega-6 consumption. That may explain the rising rates of cardiovascular disease in Asian populations.

TR: What are the major hurdles in identifying how our genes affect our body's response to food?

JO: There are so many combinations of genes and environmental factors, you need huge populations to study. Most studies in the field are underpowered. We've done studies with 5,000 people, but that's just not enough. We need to do studies on the order of 100,000 people to take into account all the different factors.

We also need better statistical tools. Currently, we are borrowing analysis tools from situations that are much simpler, such as Medelian genetics, where a single gene leads to a certain phenotype. But applying those methods to huge networks of interactions is just not feasible.

TR: Is the nutrigenomics community using new genetic tools, such as the large gene chips that can detect 500,000 genetic variations in a single experiment?

JO: Yes, those chips do help to accumulate data. But because we need to run thousands of subjects, the cost is still prohibitive.

TR: A few consumer nutrigenomics tests are already on the market. What do you think of them?

JO: These tests may point people in the right direction, but they are not by far a final answer. Their worth also depends on the feedback the consumer gets. If the test is accompanied by prudent recommendations on diet and does not make snake-oil promises, then they probably don't have much potential to harm. And they may even have some benefit. One study found that people who took the test and went to a dietician did better than people who just went to a dietician. I think it's the placebo effect. People will pay better attention because they feel they are getting advice that is just for them.


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