Nutrigenomics has received a bad rap in recent years, largely because companies have been offering individually tailored cocktails of supplements based on unproven research. But research like Marini’s begins to provide a way to more rigorously analyze vitamins’ impact. The work is unique because it provides an easy way to assess gene function, something that hasn’t been done much in nutrigenomics, says Bruce Ames, a biochemist at Berkeley who helped pioneer the study of vitamins in metabolism and human health. Ames, who was not involved in the research, adds that analysis in more complex systems will likely be needed to determine optimal dosages. “In the future, scientists may take a cell from an actual person and grow it in culture to determine if a bit extra of this vitamin or that vitamin can help,” he says.
Marini, Rine, and their colleagues are now following up their research in humans to try to better understand the enzyme’s role in birth defects. In collaboration with the Children’s Hospital Oakland Research Institute and the Joint Genome Center, in Walnut Creek, CA, the scientists will sequence the gene in 250 children with neural-tube defects and 250 normal children to see whether the poorly functioning variants appear more often in the former. “This could be incredibly important for shedding light on birth defects,” says Gary Shaw, the research director for the California Research Division of the March of Dimes, who is based at the Children’s Hospital Oakland Research Institute.
The Berkeley research has been enabled by new technologies, such as inexpensive gene sequencing, that allow scientists to search for a multitude of rare variants unlikely to be detected with other genetic tools. “We think that low-frequency variations, which would only be identified through sequencing, are important,” says Marini. For example, scientists have long known that there is a genetic component to neural-tube defects, because a woman who gives birth to one affected child is likely to have another. “But it’s been difficult to pinpoint the genetic cause, probably because it’s linked to low-frequency variants,” says Marini.
The findings might also shed light on a growing controversy over folate and heart disease. The MTHFR enzyme breaks down homocysteine, an amino acid that has been linked to heart disease in some studies but not others. An ineffective enzyme causes homocysteine to build up in the blood. It’s possible that only people who have both an ineffective enzyme and low levels of folate sustain high levels of the amino acid long enough to cause harm, says Syed Hussein Askree, a postdoctoral researcher in Ames’s lab. Because most studies examine people with a range of genotypes and diets, that link may have gotten lost.
Ultimately, Marini and his collaborators hope to take a much broader look at our nutritional requirements. Based on the rate of rare genetic impairments within the MTHFR region, the researchers calculated that everyone harbors about 250 disadvantageous mutations amid the 600 enzymes that require vitamins or minerals to function. That might mean we’re missing out on a lot of vitamins.