Yasko Methylation

See also Talk:Yasko Methylation for additional discussion

The scientific credentials of Dr. Amy Yasko are strongly questioned by these sources:

While these are generally trusting

Dr. Amy Yasko is primarily known for her work with autistic children, but she also works with adults who have neurological conditions. There is some significant patient interest in the areas of Chronic Fatigue Syndrome and Fibromylagia. Her treatment is based on the idea that patients have certain genetic flaws which are then stressed by real-world conditions (diets, medicines, toxins, infection, stress, etc). While genetic tests are done at the beginning of an evaluation, they are also confirmed by lab tests which demonstrate the genetic weaknesses. Later, those lab tests are used to measure progress. So the components of Yasko are genetic testing, lab testing, custom expert advice, diet and supplement changes over a period of time, and back to lab testing to review progress and to make changes.

The following explanations of the SNPs are from a number of sources, although specific SNPS, the categories, and the behavioral effects are mostly from the Web page and writings of Yasko herself. Although supplements, dietary changes, or interactions may be listed below, nothing here should be considered medical advice. If you are interested in pursuing Yasko Methylation, your best option might be to become a patient of Dr. Yasko. Those who are curious about Yasko, and or Dr. Rawlins' MTHFR Nutritional Protocol) might find these SNPs useful.

ACE Gene[edit]

rs4343 - ACE Del16 (Use this substitute SNP as a very reliable proxy.) (Risk Allele: G)

This enzymes leads to high levels of angiotensin II which causes an increase in aldosterone. High aldosterone leads to increase potassium loss in the urine and increased sodium retention. Animal studies show a correlation between high angiotensin II with increased anxiety and decreased learning and memory. Decreased potassium can lead to fatigue and decreased energy production as cellular membrane activation, particularly for the brain and peripheral nervous system is dependent upon sodium:potassium balance. Blood pressure regulation as well. Low frustration threshold. Increased anxiety. Worsened by stress. An MAO-A mutation makes this worse. The ACE Del16 mutation may have been removed from Yasko's current genetic tests.

COMT Gene[edit]

rs4680 - COMT V158M (Risk Allele: A)
rs4633 - COMT H62H (Risk Allele: T)
rs769224 - COMT P199P (Risk Allele: A)

This gene helps break down dopamine and norepinephrine. A defect will cause higher dopamine due to slower breakdown. Implicated in ADD/ADHD. More susceptible to dopamine fluctuations, therefore mood swings. People without COMT mutations are generally more even tempered.

VDR Gene[edit]

rs1544410 - VDR Bsm (Risk Allele: T)
rs731236 - VDR Taq (Risk Allele: A)
rs10735810 - VDR Fok (Risk Allele: T, 23andMe: A)

Vitamin D receptor. VDR Fok is involved with Blood sugar regulation. VDR mutations oppose COMT mutations in the regulation of dopamine levels. A VDR mutation means that a person is less sensitive to methyl group supplement levels. (Mood swings.) A VDR mutation can result in behaviors opposite to a COMT mutation. See Dr. Roberts comments at http://www.heartfixer.com/AMRI-Nutrigenomics.htm#VDR%20Taq:%20%20Vitamin%20D%20Receptor%20Taq%20Abnormality

MAOA Gene[edit]

rs6323 - MAOA R297R (Risk Allele: T)

Slower breakdown of Serotonin. Can lead to high/low cycling of neurotransmitter. This enzyme requires B2 (riboflavin) in sufficient levels to function normally. Mutations are associated with mood swings, aggressive behavior, depression, anxiety, OCD and intolerance of methylfolate (which increases neurotransmitters that can't be broken down by MAO A,causing feelings of overstimulation). ACE deletions will also increase anxiety and lower frustration thresholds. Because this is on the X chromosome, males will have only one allele.

ACAT1 Gene[edit]

rs3741049 - ACAT1-02 (Risk Allele: A)

Plays a major role in ketone body metabolism. Defects cause a 3-ketothiolase deficiency. Yasko believes it will cause an increase in gut bugs (particularly clostridia) as well as elevated fatty acid metabolites.

MTHFR Gene[edit]

rs1801133 - MTHFR C677T (Risk Allele: A)
rs1801131 - MTHFR A1298C (Risk Allele: G)
rs2066470 - MTHFR P39P (Risk Allele: A)

MTHFR mutations are the centerpiece of the work by Yasko, Rawlins and others, and is the most important to understand. An MTHFR mutation can starve the entire methylation cycle, which has some very large health impacts.

The C677T mutation is associated with a general set of problems: elevated homocysteine, increase in heart disease, increased stroke, increased deep vein thrombosis, peripheral neuropathy, placental vascular problems (stillbirth), preeclampsia, neural tube defects, cleft lip.

The A1298C mutation is assoicated with a second set of problems: depression, anxiety, irritable bowel syndrome, fibromyalgia, chronic fatigue, migraines, dementia, nerve pain, schizophrenia, parkinson's, tetrahydrobiopterin (BH4) problems. Although not addressed by Yasko, if your Promethease report includes Gs223 or Gs224, you may have additional BH4 impairment.

A person who is compound heterozygous (a single C677T mutation and a single A1298C mutation, each on a different strand) will see symptoms from both defects, but the symptoms tend to be more severe. Rawlins also believes that blood clots are more prevalent. As bad as that is, a person with a single mutation on one gene and a double mutation on the other can be worse. A person who is compound homozygous (double mutation on both genes) is also worse.

MTR Gene[edit]

rs1805087 - MTR A2576G (Risk Allele: G)

Helps produce methionine from homocysteine. Likely needs a methylated B12. A mutation here causes increase function and increased methyl group depletion. This can be made worse by MTRR mutations.

MTRR Gene[edit]

rs1801394 - MTRR A66G (Risk Allele: G)
rs10380 - MTRR H595Y (Risk Allele: T)
rs162036 - MTRR L350A (Risk Allele: G)
rs2287780 - MTRR R415T (Risk Allele: T)
rs2303080 - MTRR S257T (Risk Allele: T)
rs1802059 - MTRR A664A (Risk Allele: A)

Necessary to regenerate Methyl-B12 for use by MTR. Mutation can cause shortage, suggesting a need for more B12.

BHMT Gene[edit]

rs585800 - BHMT-01 (Risk Allele: T)
rs567754 - BHMT-02 (Risk Allele: T)
rs617219 - BHMT-04 (Risk Allele: C)
rs651852 - BHMT-08 (Risk Allele: A, 23andMe: T)

The product the BHMT gene is central to the ‘short cut’ through the methylation cycle, again helping to convert homocysteine to methionine. The activity of this gene product can be affected by stress, by cortisol levels and may play a role in ADD/ADHD by affecting norepinephrine levels.

Yasko believes that believes BHMT-02 and BHMT-04 play a role in the gut environment. Yasko also believes that BHMT-08 is related to the impact that psychological stress has on a patient's attention levels.

AHCY Gene[edit]

rs819147 - AHCY-01 (Risk Allele: C)
rs819134 - AHCY-02 (Risk Allele: G)
- (Why does this say the risk allele is "G" when dbSNP lists "G" as the "Ancestral Allele"?)
- The Population diversity data shows that G is more common in African populations, but that A is more common in european, chinese, and hispanic populations. Neither of our data points 'explains' it, but since older alleles can be considered risk alleles (see APOE4) there doesn't necessarily appear to be a conflict.
rs819171 - AHCY-19 (Risk Allele: C)

Catalyzes the hydrolysis of AdoHcy to adenosine and homocysteine. AdoHcy hydrolysis serves not only to sustain the flux of methionine sulfur toward cysteine, but is believed also to play a critical role in the regulation of biologic methylations.

CBS Gene[edit]

rs234706 - CBS C699T (Risk Allele: A)
rs1801181 - CBS A360A (Risk Allele: T, 23andMe: A)
rs2298758 - CBS I278T (Risk Allele: G)

Limits homocystine into downstream path. People with CBS mutations will need to be careful with sulfur containing supplements. Increased risk for ammonia detoxification issues. Puts a burden on SUOX.

http://web.mit.edu/london/www/cbs.html summary of CBS literature casts doubt on the relevance of these mutations

SUOX Gene[edit]

rs773115 - SUOX S370S (Risk Allele: C)
- an anonymous edit provided the rs#, however that is a synonymous change, and the location doesn't seem correct. However http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?locusId=6821 fails to list any snp at 370, so the true rs# remains uncertain.
rs7297662 - SUOX A628C

This gene product helps to detoxify sulfites in the body. Sulfites are a natural byproduct of the methylation cycle and are also ingested from foods. Made worse with CBS and NOS mutations.

NOS3 Gene[edit]

rs1799983 - NOS-3 D298E (Risk Allele: T)

Helps in the formation of nitric oxide which has a role in ammonia detoxification, oxidative stress, vascular relaxation and chemical production. Mutations here are made worse by MTHFR A1298C mutations and CBS mutations. A mutation here is also made worse by a lack of mutations in SUOX.

SHMT1 Gene[edit]

rs1979277 - SHMT-1 C1420T (Risk Allele: A)

Helps to shift the emphasis of the methylation cycle toward the building blocks needed for new DNA synthesis and away from the processing of homocysteine to methionine.