Follow-up to: Individual Risk: The Influence of Single Nucleotide Polymorphisms, Nutrient Deficiencies, Synergism of Simultaneous Exposures on Total Body Burden, and the Manifestation of Disease
We received several comments/questions after Steve Ottersberg's lecture on how to apply the principles of snps and detoxification in patient care. So I thought I would fill in a few blanks.
First here is a recent article by Jeffrey Bland and Deanna Minich outlining the rationale and some of the data behind the efficacy of personalized medicine: Personalized Lifestyle Medicine.
And another short but relevant article on the topic of Detoxigenetics: In Search of Host Susceptibility to Environmental Toxicants
I'll come back to this last article in a few minutes so you might want to read it before moving on here.
The $99.00 panel for saliva-derived gene polymorphisms that are offered direct to patients by 23andme have some drawbacks (contamination with bacteria that may have sulfite oxidase (SUOX) snps) but the affordability of the test may make up for the reliability of that specific snp. The Illumina chip that they use tests for over 200,000 snps plus 30,000 they have identified from the medical literature that correlate with disease states. Blood testing with Amy Yasko PhD, who runs and interprets personalized snp profiles for autistic children, charges $500.00 for the panels of specific snps she has found to be helpful in this population (no affiliation although I do think she deserves attention).
Personalized lifestyle medicine, as it's being called, is becoming more and more popular in medical and academic circles, particularly with current research on MTHFR variants and remission of depression in those who had previously failed SSRI therapy.
Fortunately, you don't need to have the methylation snps, their effects, or interventions memorized. Dr Jim Roberts, a nutrition-oriented cardiologist has utilized the work of Amy Yasko and created a page on his practice website on Nutrigenomics that, in great detail, explains all of the methylation snps, their place in the cycle, and suggested nutrient supplementation for each.
What is less well-recognized, evaluated or utilized in integrative medical practice, but equally important, is the role of snps in "detoxification" or as we like to correctly term it: biotransformation. Let's take a look at some 23andme results:
Here are the results of one 23andme salivary gene array testing that is then put through the no-cost analysis at www.geneticgenie.org to produce two panels: Methylation Profile
and a summary of all of the heterozygous and homozygous mutations involved in methylation and sulfation:
and a "Detox Profile" (or maybe more aptly a "Biotransformation Profile")
For now, I'm just going to address the Biotransformation snps.
Dr. Merritt will talk more about methylation snps and lead toxicity/chelation in her upcoming lecture.
And now, about that toxicogenetics article I linked above:
It has been reported that organochlorine insecticides are present at a higher concentration in tissues of Parkinson's Disease patients, which may partly explain the association between PD and polymorphisms within the CYP2D6 gene. A recent meta-analysis did show a significant increased risk for PD in those with the CYP2D6*4 snp.
This relationship iincludes risk for Parkinson's Disease after exposure to paraquat a combination that gives an 11 times increased odds ratio to those in the study with a CYP2D6*4 snp. Why? Because CYP2D6 is the pathway for biotransformation and elimination of most herbicides and pesticides as well as about 25% of pharmaceuticals.
Individuals with the CYP2D6*4 mutation, the most common CYP2S6 snp, produces non- functioning 2D6 enzymes. What does this mean? From the study linked above: "About 5–10% of white populations are homozygous for the allele and for them the enzyme activity is practically undetectable" Slowly metabolized pesticides and herbicides have increased carcinogenicity and neurotoxicity. The panel above does not show evidence of CYP2D6 snps but if it did and that individual had a occupational history of organochlorine exposure, especially if they exhibiting early signs of PD (anosmia, sleep disturbance, tremor, soft voice, episodic dizziness, etc.) -an appropriate intervention may be not only to initiate a process of decreasing body burden (Dr. Genuis will lecture on this January 5th) through medical sauna, but also initiate a protocol to decrease the neurotoxicity of organochlorine pesticides via safe pancreatic-lipase inhibitors. Read Dr. Genuis' article on this subject for a thorough education on reducing organochlorine pesticide body burden.
Finally, this panel also shows a null GSTT1. GSTT1 deletions are related to development of colorectal and lung cancer as well as gastric cancer in a Chinese population and invasive ductal breast cancer in women with both the GSTM1 and GSTT1 mutation. Glutathione S-transferase (GST) enzymes are found in the liver, gut, brain and other tissues and are involved in detoxification of a variety of endogenous and exogenous substances and protect tissues against oxidant stress. The two snps of the GSTT and GSTM variants (GSTT1*0 and GSTM1*0) are deletions, meaning that variant of the enzyme has no activity. Approximately 50 and 20% of Caucasians are homozygous for the GSTM1∗0 and GSTT1∗0 genotypes, respectively. A study of GSTT1 homozygous mutation holders that had been exposed to paraquat were shown to be at 11 times increased risk of PD compared to those without the mutation who WERE exposed to paraquat.
Unfortunately our patient whose panel is listed above DOES have a GSTT1 deletion and DOES have an occupational exposure to paraquat (one of the most widely used herbicides in the world) and does have early symptoms of PD. What is our intelligent intervention for her? I'll talk about GSTT1 and GSTM1 deletions at length next week, until then, let me know what YOU suggest. Remember this is not a glutathione deficiency, it's a gene mutation that prevents glutathione from forming a conjugate with a toxic molecule. How can we intervene and decrease risk from toxicant-induced disease? Does supplementing with glutathione precursors (ALA, NAC, etc.) improve the functional effect of GST enzymes? STAY TUNED. Best, Lyn Patrick
