Published in The Scientist, September 2006:
Jose M. Ordovas has been studying the role of lipoproteins in heart disease for decades. His laboratory and others have tried to tease out how these proteins factor into why some people
can eat an unhealthy diet – that is, lots of dietary fat – and still have high levels of what is often referred to as good high-density lipoprotein (HDL) cholesterol. The senior scientist and director of the Nutrition and Genomics Laboratory at Tufts University in Boston honed in on APOA1, which encodes the HDL component apolipoprotein (apo) A-I. A specific SNP in its promoter region (APOA1 – 75G/A) was first identified in the early 1980s, and studies in the decade followin scrutinized the association between the G and A alleles and HDL concentrations. The results varied widely. Some studies suggested that carriers of the A allele (about 25% of the population) had higher HDL levels than carriers of the more common G allele, but other studies came to the exact opposite conclusion.
In 2002, he and his colleagues tested whether dietary fat might modulate the effect of the allele. “We decided to consider whether APOA1 is regulated by nutrients, since people are eating different things,” Ordovas recalls. They looked at 755 men and 822 women who were participants in the Framingham Offspring Study, a population for which there are rigorous data on HDL levels, other cardiovascular risk factors, and dietary fat intake. They paired this information with genotype data for each patient and found that the polymorphism on its own didn’t have an effect on HDL level. Instead, in people heterozygous or homozygous for the A allele, “what we found is that polyunsaturated fatty acids, which are very good regulators of gene expression, happen to modulate the expression of this genotype,” Ordovas says.
It was the sort of finding that laid the foundation for the nascent field of nutrigenomics. At its core, the field is the study of how genes and nutrients interact to promote health or disease. It also includes understanding how gene and protein expression are affected by the presence or absence of specific nutrients, whether and how diet-regulated genes play a role in disease, the degree to which an individual’s diet affects the risk of disease given his or her genetics, and whether one’s diet may be altered to maintain that balance between health and disease.