Functional Medicine in Practice: Concepts in Epigenetics and Nutrigenomics
FUNCTIONAL MEDICINE
Laurie Mueller
DC, CFMP
Genetics 101
As a quick refresher, human beings have 23 pairs of chromosomes. Each chromosome has a given number of genes ranging from 50 to 2,000. Those genes—over 20,000 in total— are made up of base pairs that can total in the hundreds of millions when added together. A nucleotide refers to those base pairs held together with the backbone/bookends of the double helix structure on each side, and those bookends are made of sugar-phosphate chemical bonds. All of these goodies live in the cell nucleus (nuclear DNA). DNA carries the full instructions or blueprint for everything we need to survive, develop, grow, reproduce, and, of course, our cellular functions and characteristics in general. DNA itself has over 3 billion nucleotide bases. As a side note, some can be found in the powerhouses of our cells called the mitochondria, where it is termed mitochondrial DNA or mtDNA. We will get more in-depth into mitochondrial action in a future article.
For now, let’s focus our magnifying glass back down to the level of those 20,000 genes. Each gene carries a specific sequence of bases that provide instructions on how to make important proteins that trigger the various biological and biochemical actions needed to carry out the functions of life. Information is stored as code sequences using four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). Adenine and guanine are purine bases, and cytosine and thymine are pyrimidines. Another part of this puzzle is that adenine always binds to thymine, while cytosine and guanine always bind to one another (also known as complementary base pairing). Another term to recall is “codon.” A codon is a sequence of three DNA or RNA nucleotides that corresponds with a specific amino acid or corresponds to a stop signal during protein synthesis. The order of the bases relates to one of 20 amino acids and has 64 possible permutations of the three-base sequence. Of the 64 codons, 61 are related to amino acids and three are classified as stop codons. For example, the codon CAG represents the amino acid glutamine; TAA represents a stop codon.
The order or sequence of bases will determine the information available for building and maintaining an organism. So, as we previously stated, human DNA as a whole consists of about 3 billion total base units, and interestingly, more than 99% of those bases are the same in all people.
What is Epigenetics?
When we talk about epigenetics, there are a lot of grandiose definitions out there, but I like simple. Epigenetics is the study of turning the function of a gene on or off. Think of each gene as a light switch. The switch itself is the DNA, and we can’t change what we inherited (we are not modifying DNA here). However, what we can help control is the finger (stimulus) that is turning on and off the switch of expression in a given patient. Epigenetics is about how we can influence that finger and thus the expression of a gene; it affects how genes are read by cells and then how the cells react. Changes in gene sequences can affect the function of the affected gene and change (stimulate or suppress) the function that the gene is supposed to perform. Sometimes it is beneficial that a gene is “on” because we want that function in our body, but sometimes we want it to stay “off’ (such as in the generation of breast cancer cells). What is really intriguing and powerful about this is the way that nutrition, environmental factors, and lifestyle can toggle genes on and off.
When We Find Variants
A SNP (pronounced “snip”) stands for “single nucleotide polymorphism.” SNPs are locations within the human genome where the type of nucleotide sequence present (containing A, T, G, or C) can differ between individuals. Some doctors call them “mutations.” In functional medicine, we prefer words such as “variant” or “different.” Let’s face it—patients sometimes panic when words such as mutation are uttered about them. SNPs are the most common type of genetic variation found among people. At least 1% of the population must contain the same variation for it to formally be classified as a SNP. Scientists believe that SNPs occur roughly every 300 nucleotides, and since we have around 3 billion nucleotides, there are approximately 10 million SNPs. Since it has been determined that over 99% of the genome is identical between individuals, SNPs actually provide researchers with a way to study genetic root differences that we find across humanity.
Most SNPs don’t have a direct effect on health, but some do. The identification of disease-causing variations is an important first step in how we can help those patients implement interventions that will make a difference. There are lab-testing panels available to look more deeply into a patient’s genetics and information that can be applied based on those findings. That is where nutrigenomics comes into play.
Nutrigenomics
Nutrigenomics refers to the study of how the nutrients (or toxins for that matter) that we take in influence the expression of our genetic framework. So what can we consume or not consume to make the changes we desire to try to flip that switch in the desired direction?
There are lengthy lists of SNPs that could come into play, but a couple of examples of SNPs that practitioners might find with genetic testing are provided here so that you can start to see how this information might be used clinically. Besides nutritional thoughts that might be mentioned, the role of the gut, detox, and immune health cannot be underestimated for these folks.
MTHFR: MTHFR stands for “methylenetetrahydrofolate reductase,” which is an enzyme that helps convert folate from the diet into a bioactive form that the body can use. Methylation is a very hot topic in medicine right now, and gene profiles can test up to 103 gene locations in their panels. The most commonly studied gene locations include c677T and/or A1298C. The lack of proper MTHFR function may change the way that some people metabolize nutrients into active vitamins, particularly folate. A SNP in these locations can alter neurotransmitter and hormone levels, increase homocysteine levels, and contribute to GI issues, cardiovascular problems, and even depression. This SNP has also been correlated with fibromyalgia and fatigue. These patients may require natural folate in the diet (not folic acid, which is synthetic B9). Often, they are also low in B6 and B9 as well. Some patients need to take a 5-MTHF supplement (the bioactive form of folate ) to bypass their lack of enzyme production. We will look at this mechanism and the process of methylation much more closely in a future article.
COMT: COMT stands for “catechol-O-methyltransferase.” Genetic panels may look at nine genes and 53 possible SNPs. COMT SNP locations often can manifest in mental health symptoms. One of the enzymes that may be affected is responsible for the degradation of catecholamines, which includes dopamine, epinephrine, and norepinephrine. This has a role in mental disorders, including bipolar disorder, depression, and anxiety, and can make individuals more susceptible to the effects of stress. We now know that COMT SNPs are fairly common. As a matter of fact, 80% of the population has a SNP in the COMT V128M gene, which slows down the COMT system by 300%. For these patients, COMT and MAO nutritional protocols for brain support as well as lifestyles that focus on stress reduction may be indicated.
Detox Genes: These include cytochrome P450s, sulfur transferases, glutathione transferases (glutathione being the mother of all antioxidants in the body), and the methyltransferases. The P450s are important for multiple molecular functions, including drug metabolism, hormone production, toxicant detoxification, and more. The P450s are expressed throughout the body, but primarily in the liver. There are 57 different genes for the cytochrome P450 enzymes, and eight of those are responsible for most of the drug metabolism done by the body. The P450 enzymes are responsible for 75% of all drug metabolism. Mutations to P450s can cause changes in the rate of metabolism of some medications, resulting in decreased effectiveness and other dangerous complications. Some medications known to be affected by drug mutations include but are certainly not limited to warfarin, diazepam, antiarrhythmic drugs, antidepressants, and antipsychotics. (12-13) P450s that are known to have alleles in the population that dramatically affect drug metabolism include CYP2C9, CYP2C19, andCYP2D6. (14) Besides the P450s, which are considered phase I detoxification, GPL-SNP1000 covers phase II detoxification enzymes that include glutathione S-transferase, sulfotransferase lal, betaine-homocysteine methyltransferase 2, andUDP glucuronosyltransferase 1A1. In these patients, support and nutrients for phase I and phase II detoxification are often warranted. A future article will be dedicated to detox phases and foods that naturally support detox processes.
References:
1. https://www.greatplainslaboratory.eom/articles-l/2016/3/3/ genetic-testing-the-key-to-traly-personalized-medicine
2. Deloughery TG, Evans A, Sadeghi A, et al. Common mutation in methylenetetrahydrofolate reductase. Correlation with homocysteine metabolism and late-onset vascular disease. Circulation. 1996;94(12):3074-3078.
3. Craddock N, Owen MJ, O'Donovan MC. The catechol-O-methyl transferase (COMT) gene as a candidate for psychiatric phenotypes: evidence and lessons. Mol Psychiatry. 2006;ll(5):446-458.
4. Guengerich FP. Mechanisms of drug toxicity and relevance to pharmaceutical development. Drug Metab Pharmacokinet. 2011;26(1):3-14. Ingelman-Sundberg M. Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Phannacogenomics J. 2005;5(1):6-13.
5. Ingelman-Sundberg M. Genetic susceptibility to adverse effects of drags and environmental toxicants. The role of the CYP family of enzymes. Mutat Res. 2001;482(1-2):11-19.
6. Kalra BS. Cytochrome P450 enzyme isofonns and their therapeutic implications: an update. Indian J Med Sci. 2007;61(2): 102-116.
7. https://ghr.nhn.nih.gov/primer/basics/dna
Laurie Mueller, BA, DC, CFMP served in private practice in San Diego, California. She was the post-graduate director at Palmer College from 2000-2010; served as the ACC Post Graduate subcommittee chair for 6 years; and peer reviewed for the Research Agenda Conference. Dr. Mueller currently works as a private eLearning consultant M>ith a focus on healthcare topics and functional medicine through her company. Impact Writing Solutions, LLC. She is a consultant, clinician, an educator and an expert in online educational pedagogy and is the founder of www. FxMedOnline. com.
