The “Omics” revolution represents truly personalized, precision medicine. The term “omics” has penetrated virtually every field of medicine – from cancer treatment, to medication management, to personalized diet and lifestyle interventions for chronic disease treatment and prevention. In this article, we will provide an overview of some of the ways genomics is being used today to create better health outcomes more efficiently and effectively.
Genes provide the blueprint for all the proteins that run our biological systems, and a person’s unique DNA profile is called a genotype. Small variations in genes called single nucleotide polymorphisms (SNPs, pronounced “snips”) can potentially increase the risk of disease by altering the function of the proteins they produce – leading to disruption in biochemical and metabolic pathways. Interactions with environmental variables can further exacerbate the impact of these gene SNPs.
Results from the Human Genome Project and the 1,000 Genomes Project Consortium have provided the springboard to new scientific disciplines, such as functional genomics and personalized genomics. These disciplines, in turn, promote the development of improved diagnostic testing, treatment and prevention strategies. Some refer to this endeavor as the Precision Medicine Initiative, for others it simply falls under the umbrella of genomics. Regardless of what you call it, genomics has and will continue to transform medicine – one person at a time.
The integration of genomics with clinical medicine is probably best illustrated today in the area of pharmacogenomics. By “unzipping” a person’s DNA, gene SNPs associated with a response to over-the-counter and prescribed medications can be identified, and guide more precise selection and dosing of medications.
Adverse medication reactions are becoming an increasingly prevalent problem, estimated to cost more than $3 billion annually. More than 50 percent of American adults using at least one pharmaceutical intervention on a regular basis, whereas 15 percent using five or more medications each day. Clinicians using pharmacogenomic testing can dramatically improve patient outcomes, and save everyone time and money.
Adverse reactions can be caused by gene-medication interactions as well as drug-drug interactions. Genes also can affect the efficacy of medications in an individual. For example, many common opioids are actually prodrugs, and must be converted into an active form in the liver to have the desired effect. This conversion is under the control of specific genes, including CYP2D6. An individual with a unique genotype of slow metabolizer for the enzyme CYP2D6, will have inefficient conversion of the parent compound, codeine, to the active one – morphine.
The net effect is that the patient does not get the expected pain relief from the medication. Knowing this genotypic information about a person beforehand allows the clinician to choose a different medication to effectively treat that person’s pain.
In contrast, a fast metabolizer genotype for CYP2D6 has an increased risk of morphine toxicity due to more rapid conversion of codeine to morphine. Excessive amounts of morphine can lead to morphine toxicity, causing severe complications and even death. A clinician can then opt to lower the dose of codeine for the person with this genotype.
Pharmacogenomic testing can be even more effective as a preventative tool. Based on known population frequencies of the 12 genes most commonly tested in pharmacogenomics, 99 percent of the population is likely to have a SNP in at least one of these genes.
A recent study by the Mayo Clinic confirmed this. The research showed that 99 percent of study subjects had at least one of the five tested pharmacogenomic gene variants. They also found that 89 percent had two or more gene variants that could compromise normal drug metabolism.
These data support proactively testing a person’s genotype before prescribing a medication to avoid adverse drug reactions, or choosing ineffective medications with a delay in desired treatment.
Nutrition scientists utilize a subcategory of genomics called nutritional genomics to better understand why people respond differently to the foods they eat. Nutritional genomics is the study of how a person’s genes and food interact. Some researchers believe this food-gene interaction can explain why recommending a one-size-fits-all diet has been ineffective in stemming the tide of diet and lifestyle-related chronic disease such as obesity, cardiac disease and diabetes.
Furthermore, nutritional genomics can explain why some people are predisposed to diabetes or obesity when they consume a high carbohydrate diet; why certain foods are more helpful in mitigating health issues in some people but not others; and why nutritional requirements can vary from person to person. By understanding a person’s genotype, dietary interventions can be personalized to each individual.
The field of nutritional genomics is subdivided into two areas: nutrigenetics and nutrigenomics. While these terms are often used interchangeably, there are important differences.
Nutrigenetics is defined as the influence of genes on nutrient utilization, or how a person’s gene SNPs can impact the processes of nutrient absorption, digestion, assimilation and utilization.
Nutrigenomics, on the other hand, is defined as the influence of diet or dietary constituents on gene function. Dietary components have been shown to “talk” to genes, either up-regulating or down-regulating gene expression and bestowing a health benefit on the individual.
An example of nutrigenetics is omega-3 fatty acid metabolism, of which EPA and DHA are best known. EPA is critical in controlling inflammation that is linked to many diseases, and DHA is an essential nutrient needed for brain development. While the primary source of EPA and DHA is cold-water fish, omega-3 fatty acids are also found in walnuts, flaxseed and chia seeds. However, these plant-based omega 3 fatty acids must be converted to EPA by an enzyme called delta-5-desaturase., which is encoded by the FADS1 gene.
A SNP on the FADS1 gene impairs activity of the enzyme, resulting in reduced production of EPA. For the person that relies solely on plant based omega-3 sources, there is a risk of an EPA deficiency. Because EPA is the precursor to DHA, this can also result in DHA deficiency. Individuals with this unique genotype profile must either incorporate fish or EPA/DHA supplements into their diet for optimal health.
An example of nutrigenomics is related to our built-in antioxidant defense system. This system is responsible for protecting DNA from damage that can lead to cancer, disease, and premature aging. This system needs nutrients, called co-factors, to help the enzymes function optimally. These are supplied through diet in the form of vitamins and minerals. Vitamins A, C, E and selenium are examples of these critical nutrients, and are often known as “antioxidants”.
There are other components of foods that also affect enzyme activity through regulation of the genes that encode them. These are called bioactives. Some of the most commonly known bioactives are flavones, including resveratrol, which are found in foods such as berries and red wine. These bioactives “turn on” the genes that produce the enzymes involved in this built-in antioxidant response, providing cellular protection against highly reactive molecules.
Nrf2 is called the “master gene” of this antioxidant system; it controls the response of many other genes that make up this biological system. But, if a person has gene SNPs on any of these genes, including Nrf2, the antioxidant response system is impaired—no longer quenching these highly reactive molecules that lead to cellular and DNA damage.
Knowing a person’s genotype gives a clinician insight into where the antioxidant response may be under-performing, and to what degree extra support is needed. A personalized roadmap based on a person’s genomic test results can be created to provide the right nutrients and bioactives to optimize the antioxidant response, and minimize lifestyle and environmental factors that can put extra burden on this system.
Nutritional genomics is most effective when used as part of a comprehensive health strategy guided by an individual’s unique genotype and DNA.
Genomic medicine is revolutionizing healthcare, improving health outcomes through personalization of diet, lifestyle, and medication management. This approach also saves resources – time and money – by utilizing a more precise roadmap for what each individual needs to achieve optimal health.