Quelques infos sur les gènes identifiés dans ce "detox profile":
Detox cytochrome P450 phase 1: Enzymes, known collectively as the cytochrome P-450 system, use oxygen to modify toxic compounds, drugs, or steroid hormones.
General Therapies to Improve Detoxification:
Foods that generally improve Phase I detoxification and as well improve the efficiency of Phase II conjugation are generally recommended for individuals with CYP SNPs. These include most vegetables and fruits, but especially
cruciferous vegetables
garlic, onions
soy
grapes, berries
green and white tea
herbs and spices, particularly rosemary, basil, turmeric, cumin, poppy seeds, black pepper.
Use of H2 blockers (e.g. Cimetidine) should be avoided as these bind to the heme-containing reactive site of all CYPs inhibiting binding to toxins.
Polymorphisms detected in 2 CYP genes:
CYP1A1 (multiple SNP locations evaluated for this gene)
CYP1B1 (multiple SNP locations evaluated for this gene)
CYP genes tested but no polymorphism detected:
CYP2A6 - detoxifies nitrosamines and nicotine
CYP2C9 (multiple SNP locations evaluated for this gene) - detoxifies coumarin and sulfonureas.
CYP2CI9 (multiple SNP locations evaluated for this gene) - detoxifies proton-pump inhibitors (e.g. prilosec®) and many anticonvulsants (e.g. valium®).
CYP2D6 - detoxifies ~20% of all prescription drugs including tricyclics, MAOIs, SSRIs, opiates, anti-arrhythmics, beta-blockers, Cimetidine, etc.
CYP2E1 - detoxifies nitrosamines and ethanol (acetaldehyde).
CYP3A4 (multiple SNP locations evaluated for this gene) - detoxifies over 50% of all prescription medications and most steroid hormones.
Detox en phase 2:COMT (Gene makes the Catechol-O-methyl transferase enzyme) location V158MFunctions:
Methylation, in the liver & gut
primarily responsible for breaking down the neurotransmitters dopamine, epinephrine, and norepinephrine
inactivates catecholamines, catechol estrogens, and catechol drugs such as L-DOPA
My Results: SNP detected on one of the two chromosomes.
Clinical Implications of COMT SNP:
Polymorphism results in reduced COMT activity, thus decreased degradation of substrates.
Impaired estrogen metabolism, including...
Individuals carrying the M alleles (+)
have a 4-fold reduced clearance of dopamine, epinephrine and norepinephrine from neural synapses.
if taking Estrogen replacement therapy, may experience higher estrogen levels than expected
Breast cancer risk is increased with long-term estrogen replacement and in women who also have a GST polymorphism (as I do).
Genovations doesn't mention other problems with estrogen metabolism, but I have experience with some. See "For more information, below.
Due to higher amounts of synaptic dopamine, the polymorphism is associated with
improved cognition
decreased risk of schizophrenia
increased risk for some other neuropsychiatric disorders, including
depression
ADHD
anxiety and ultra rapid cycling bipolar
disorder
anti-social behavior
increased sensitivity to pain
fibromyalgia
migraine
late-onset alcoholism
possibly Parkinsons disease.
Homozygous positive bipolar patients may develop rapid cycling with methylphenidate (Ritalin).
Minimizing Risks from COMT SNP:
Avoid excessive alcohol consumption; seek help if alcohol consumption is a health issue.
Minimize sustained mental and environmental stress (stress hormones require COMT for degradation and compete with estrogens).
Ensure adequate intake of B vitamins, magnesium, and amino acids.
Avoid high homocysteine (S-adenosylhomocysteine inhibits COMT)
Antioxidants to prevent oxidation of pro-carcinogenic 4-hydroxyestrogens.
Use caution with
amphetamine-based medications
catechol drugs.
methylphenidate (Ritalin).
Consider carefully the increased risk from Estrogen replacement therapy.
Don't use quercetin: Inhibition of Catechol O-Methyltransferase-catalyzed O-Methylation of 2- and 4-Hydroxyestradiol by Quercetin. Bao Ting Zhu, Joachim G. Liehr.
NAT (N-acetyl transferase enzymes)Function: Acetylation
N-acetyltransferase 1 is found in extra-hepatic tissues
N-acetyltransferase 2 is found predominantly in the liver and the gut. NAT2 acetylates numerous environmental toxins, including
heterocyclic aromatic amines.
tobacco smoke
exhaust fumes.
Both NAT1 and NAT2 are used in the acetylation of numerous environmental toxins, including heterocyclic aromatic amines.
Slow Metabolizer NAT Polymorphism
Gene NAT1, location R64W
affects all cells
My results: no polymorphism found
Gene NAT1, location R187Q
In the liver and gut
My results: no polymorphism found
Gene NAT2, location I114T
In the liver and gut
My results: polymorphism found on one of the two chromosomes
Gene NAT2, location R197Q
In the liver & gut
My results: polymorphism found on one of the two chromosomes
Gene NAT2, location G286E
In the liver and gut
My results: no polymorphism found
Gene NAT2, location R64Q
In the liver and gut
My results: no polymorphism found
Fast Metabolizer NAT Polymorphism
Gene NAT2, location K268R
In the liver and gut
My results: polymorphism found on one of the two chromosomes
Health Implications of NAT SNPs:
Polymorphisms can result in slower than normal or faster than normal addition of an acetyl group to these toxins.
Slow acetylators
poor clearing of toxins
the resulting increased total toxic burden can increase the risk of lung, colon, breast, bladder, or head & neck cancer.
Urinary cancer appears to have the most consistent association with slow acetylation.
Rapid acetylators
add acetyl groups so rapidly that they make mistakes in the process
increase 0-acetylation of toxins that can actually make the toxins more reactive.
Colon cancer appears to have the most consistently reproducible association with fast acetylation.
Both slow and rapid acetylators are at increased risk for toxic overload if they are exposed to environmental toxins.
Minimizing Risk from NAT SNPs:
If you smoke, stop. Your risk of lung and breast cancer is substantially higher than someone with normal NAT activity.
Do not eat fried foods and minimize red meat as these substantially increase your risk of colorectal cancer.
Avoid well-done meats as these may substantially increase your risk of breast cancer.
Foods that increase acetylation: most vegetables and fruits but especially
cruciferous (cabbage-family) vegetables
garlic, onions
soy
grapes and berries
GST (Glutathione s-transferase enzymes)Functions:
The GST isoforms (M1, P1, and T1) act similarly but predominate in various tissues.
All catalyze the conjugation of electrophilic and water-soluble compounds with glutathione.
For more information see Glutathione Metabolism - Functions.
My results:
Gene GSTM1, location 1p13.3
In the liver and kidney
Test indicates that the gene is present; lab was unable to determine whether on one or both chromosomes.
Gene GSTP1, location I105V
In the brain and skin
Polymorphism found on both of the two chromosomes
Gene GSTP1, location A114V
In the brain and skin
Polymorphism found on one of the two chromosomes.
Health implications of defects in GST activity:
May increase
toxic burden
oxidative stress.
risk of
fatigue syndromes
various cancers,
particularly malignant melanoma, as well as Hodgkin's and non-Hodgkins lymphomas.
throughout the body, particularly in lung, prostate, head & neck.
GST polymorphisms should be seen as disease-modifying rather than disease-causing, likely via their role in cellular protection against cellular oxidative stress -- a risk that appears to be additive with increasing numbers of polymorphisms to various isozymes.
GST polymporphisms generally indicate a poorer prognosis in
Chronic diseases, for example multiple sclerosis and cystic fibrosis
Cancer. In particular, ovarian cancer and malignant melanoma do not respond well to chemotherapy.
Minimizing Risk from GST defects:
Regardless of genotype, increasing the body's production of glutathione will reduce oxidative stress and afford greater protection against a wide array of toxins. (But for people like me who have trouble metabolizing cysteine, this can be problematic. See My Glutathione Experience.)
Avoid substances requiring GSH to detox:
Cigarette smoke
herbicides, fungicides, insect sprays, industrial solvents.
Ginkgo biloba boosts GST -- in mice, anyway: see Studies on the constituents of edible and medicinal plants. 41. Effects of Ginkgo biloba and its terpene constituents on phase II drug-metabolizing enzymes and glutathione levels in mouse liver. Sasaki Keiko, Wada Keiji, and Haga Masanobu.
Glutathione Supplementation.
SOD (Superoxide Dismutase enzymes)Functions:
Oxidative protection: converts reactive oxygen species into less reactive hydrogen peroxide.
Protects cells from increased oxidative stress and free radical damage to cell structures like membranes, mitochondria, DNA, and proteins.
SOD1 is present in the cytosol
SOD2 is present in the mitochondria (where most of the body's energy is made) -- the primary anti-oxidant enzyme there
My SOD Results:
Gene SOD1, location G93A
In the Cytosol
No polymorphisms found
Gene SOD1, location A4V
In the Cytosol
No polymorphisms found
Gene SOD2, location A16V
In the Mitochondria
Polymorphisms found on both chromosomes
Health Implications of Polymorphisms in SOD enzymes:
Changes in the SOD enzyme are associated with higher risk of
oxidative stress and related conditions
neurodegenerative disorders like ALS.
This genotype has specifically been associated with cardiomyopathy.
Minimizing Risk from SOD Polymorphism:
Colorful vegetables and fruits
for example, banana - see Antioxidant activity of banana flavonoids. Vijayakumar S, Presannakumar G, Vijayalakshmi NR.:"The antioxidant activity of flavonoids from banana (Musa paradisiaca) was studied in rats fed normal as well as high fat diets. Concentrations of peroxidation products namely malondialdehyde, hydroperoxides and conjugated diens were significantly decreased whereas the activities of catalase and superoxide dismutase were enhanced significantly. Concentrations of glutathione were also elevated in the treated animals."
Broad-spectrum anti-oxidant supplements, including agents that help to raise glutathione levels --e.g.
vitamin C
magnesium
n-acetylcysteine (NAC)
alpha-lipoic acid
milk thistle
Manganese (a cofactor for SOD2) may also be helpful.
source:
http://www.canarys-eye-view.org/metabol ... n-ph2.html
Posté: Jeu 20 Déc 2012 16:51
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