Wednesday, July 02, 2008

Taking Vitamins Based on Your Genome

Newly discovered genetic variations could predict who needs more folic acid.

By Emily Singer

Credit: Technology Review

Newly discovered genetic variations can impair an enzyme whose malfunction has been linked to birth defects and heart disease--but added nutrients can reverse the effect, according to new research. The findings could signify a step forward for nutrigenomics, a growing field examining how our diet and genes interact to affect our health. Scientists hope that nutrigenomics research will one day help people overcome some of their genetic foibles with personally tailored cocktails of vitamins.

The daily vitamin dosages recommended by the U.S. Department of Agriculture "are based on studies done 60 years ago, and are based on the assumption that everyone is biochemically the same," says Nick Marini, a biologist at the University of California, Berkeley, who led the new research in collaboration with Jasper Rine, another Berkeley biologist. "We also think compliance would be better if an individual knew they personally needed more of a particular vitamin."

The human genome codes for approximately 600 enzymes that must interact with vitamins or minerals in order to function properly. Scientists have known for years that some rare and severe metabolic disorders, caused by misspellings in the genes for vitamin-dependant enzymes, can be treated with vitamins. But research linking such genetic variations to more subtle health effects, which might affect a much broader swath of the population, is only just beginning.

In a pilot study published in June, scientists focused on an enzyme called MTHFR, or methylenetetrahydrofolate reductase, which converts the B vitamin folate (also called folic acid) from one form into another. Folate plays many roles in maintaining human health: it's been linked to preterm birth and birth defects, as well as to cardiovascular disease, stroke, and colorectal cancer. The U.S. Food and Drug Administration mandated the addition of the vitamin to cereals and other grains in 1993.

Previous research suggested that variations in the MTHFR enzyme may make some people more susceptible to the effects of folate deficiency. A common genetic variant that produces a weakened version of the enzyme increases risk of birth defects and possibly of heart disease, although it's not clear why. About 12 percent of people of European descent have two copies of that variation.

Marini and his colleagues sequenced the MTHFR gene in 564 people of different ethnicities and found four new variants that also impair enzyme function. In a unique step, the researchers then rigged a molecular system to measure how efficiently the different forms of the enzyme could churn out their molecular products. They added the human gene sequences to yeast cells, which were engineered such that their growth rate depended on how well the enzyme was working. Three of those sequences performed poorly: the yeast cells containing them grew more slowly than their counterparts when fed limited amounts of folate. But the same yeast grew at normal rates when given the vitamin in excess, suggesting that higher doses of folate might help people who are genetically susceptible to health problems linked to B-vitamin deficiency. The findings were published in the Proceedings of the National Academy of Sciences.