Nutrigenomics and metabolomics

The next step in understanding what the human genome is telling us, especially

Despite some cosmetic differences, we all have the same genetic makeup that evolved from primitive man. Unfortunately, the genes that were in place before the advent of the earliest civilizations were not designed to carry individuals through today’s typical age span, now approximately eight decades of wear and tear. Additionally, the multiple genetic mutations that could survive in ancient times more than likely surrender to the chronic disorders that can be attributed to metabolic stress today. Thus the dramatic increase of those age-related diseases in current times.

Scientists have known that dietary patterns are strongly linked to the development of seven of the ten top causes of morbidity and mortality in the United States, primarily cardiovascular diseases, cancer, and diabetes. Consequently, a scientific and technological revolution has been going on in the areas of nutrition and biochemistry. This revolution has lead to significant new understandings of the role of food and nutrition in human health, and with the Human Genome Project, a new ability to understand the role of genetics in metabolism and health. The advancement of biotechnology into the development of genomics, proteomics (expression of proteins), and metabolomics provides new tools for establishing the role of food and nutrients in human health.

This is the focus of the upcoming presentation, “Genomics and Proteomics: Potential Role In Characterizing Risk for Coronary Heart Disease,” being offered by Jose Ordovas, PhD, United States Department of Agriculture, Human Nutrition Research Center on Aging, Tufts University, Boston, MA. His findings are being presented during the 54th Annual Meeting of the American Association for Clinical Chemistry (AACC). AACC (http://www.aacc.org/) is the scientific organization for clinical laboratory professionals, physicians, and research scientists. More than 11,000 attendees are expected for the meeting, which is being held at the Orange County Convention Center, Orlando, FL, July 28-August 1, 2002

Dr. Ordovas, a noted researcher, will present his views on how genomics, metabolomics and informatics can be used to understand how food and nutrients impact gene function and metabolism. He will also discuss the role of “metabolomics” in defining biochemical markers and the effective construction of the data into useful formats through infomatics.

This combination of various disciplines is called “Nutrigenomics,” and provides a potential for early identification of those at high risk to metabolic stress and to understand the molecular basis of physiological defects. This has the potential for providing the tools for a more personalized and effective dietary intervention that in some cases may need to be combined with pharmacological therapy.

Background

In the last five million years, our genes have not changed significantly. This is shown by the common occurrence of many genetic variants in all different ethnic groups. Early humans were hunters and gatherers, close to nature, with little obesity. Modern man has a high “waist-to-hip” ratio (obesity) but his genes evolved unable to cope with metabolic stress resulting from the high caloric, high saturated fat diets.

Key to the ability to survive in spite of metabolic stress is the presence of “survival” genetic alleles that in combination with the proper environment will allow them to reach the maximum life span in relatively good health. On the other hand, certain individuals carry predisposing mutations (or polymorphisms) that in combination with the wrong environment will shorten their lives. These subjects will die in their fifties and sixties (or even earlier) from heart disease, cancer, diabetes and other chronic disorders. The extreme situation will be represented by those subjects with genetic diseases, such as familial hypercholesterolemia, who will perish to the disease before their forties.

Cardiovascular disease is the number one killer in the United States and in most industrialized countries and serves to illustrate some of the current advances in nutrigenomics. High-density lipoproteins (HDL) have received the familial name of carriers of the “good cholesterol”. This is based on the evidence that increasing concentrations in blood are protective for coronary heart disease (CHD). The major protein in HDL is apoA-I and this is coded by the APOA1 gene. This gene is part of the APOA1-C3-A4 gene complex on chromosome 11 here showing some of the common polymorphism. Dr. Ordovas’ research efforts have demonstrated that the apoC-III/SstI polymorphism may be quite relevant for non-insulin dependent diabetes mellitus (NIDDM) and interaction with dietary habits and ethnicity. Accordingly, the ApoA-IV 360 polymorphism is a marker of dietary response.

Dr. Ordovas believes we now have access to the technology that is allowing us to move forward into the nutrigenomics and later on into the full spectrum of the “-omics” involved in functional genomics. This will allow in furthering understanding of the variant genes, or phenotypes under consideration. The goal of the “-omics” effort is to reach the scientific dream of understanding the complex biochemical pathways and their interaction with the hope of being able to control them and to achieve the maximum life expectancy with the highest quality of life.

Editor’s Note: To interview Dr. Ordovas, please contact Donna Krupa at 703.527.7357 (direct dial), 703.967.2751 (cell) or djkrupa1@aol.com.
Or contact the AACC Newsroom at: 407.685.4215.