DNA Notes 4 Docs

Excerpts from my Genetics Report 

These are some things that I found in my DNA test that are either of concern or that warrant looking into in order to explain symptoms that are not Hashimoto's. 

Basic: Few marks for increased risk for obesity, heart issues,  diabetes; but all of those come with Hashimoto's so nothing really extra to look out for. Even said “fat gene” which gave me a chuckle. Also found certain cancer vulnerabilities, Alzheimer's and ischemic stroke. Increased risk of  all forms of macular degeneration: consider a diet rich in vitamins C and E, lutein, zeaxanthin and the minerals zinc and copper.

Major Health:

Carrier for PKU, still check my phe and other amino levels to see if there is any issue in toxin build up, it explains many symptoms. One DNA test said carrier, other said I had it. Wouldn't hurt to check my levels to be sure. 

You have one copy of GCH1 variant associated with lower levels of tetrahydrobiopterin. Those with two copies of this haplotype will likely have somewhat reduced levels of tetrahydrobiopterin. This plays into phenylalanine break down into tyrosine and the synthesis into the other neurotransmitters, the problem with PKU. This just strengthens the need to check my amino acid levels and treat if necessary.

Congenital adrenal hyperplasia. Again, needs to be double checked. One found it and the other fully questioned if it was a valid find. It does explain many adrenal and hormone symptoms though.

Metabolic Syndrome- Pro12Ala, is a common SNP in the peroxisome proliferator-activated receptor PPARG gene, associated with metabolic syndrome. I had a few more genes for this. 

AMPD1 deficiency heterozygous .The AMPD1 gene encodes the enzyme adenosine monophosphate deaminase, which is one of the key enzymes used to process the energy source ATP. The C34T variation causes a premature stop in the protein, leading to a nonfunctional AMPD1 enzyme. Some individuals - but by no means all or even a majority apparently - who are AMPD1 deficient get muscle cramps and pains when they exert themselves. Perhaps this is a piece of the puzzle as to why I have the over exertion, temporary paralysis, and muscle loss when I exert myself. 

Reduced conversion of beta-carotene to retinol. Female volunteers carrying at least one T in SNPs Rs7501331 and Rs12934922 show a 69% lower ability to convert Beta-carotene into retinyl esters. 

- Reduced conversion of beta-carotene to retinol. Reduced BCMO1 activity results in 32% lower ability to convert Beta-carotene to retinyl esters and higher serum beta-carotene levels 

MTHFR polymorphisms affecting homocysteine. You have a combination of 2 SNP variations in MTHFR which influence homocysteine levels.  Elevates homocysteine levels, lowers the ability to process folate, leads to chronic b12 deficiency. 

Higher IL6; certain risks, see details rs1800795 is a SNP in the promoter of the interleukin-6 IL6 gene, affecting the levels made of this important cytokine. In the literature, it is almost universally referred to as the IL6 '-174' polymorphism. 

Epistatic interactions between HLA-DRB1 and interleukin 4, but not interferon-gamma, increase susceptibility to giant cell arteritis. Cytokine polymorphisms in the Th1/Th2 pathway and susceptibility to non-Hodgkin lymphoma. A functional SNP of interferon-gamma gene is important for interferon-alpha-induced and spontaneous recovery from hepatitis C virus infection. Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival. A single nucleotide polymorphism (A --> G) in intron 3 of IFNgamma gene is associated with asthma. Host immune gene polymorphisms in combination with clinical and demographic factors predict late survival in diffuse large B-cell lymphoma patients in the pre-rituximab era. 

Listed reactive CMV and EBV after initial infections. Has to do with Vit D and IL-10.  More cytokine problems.

Rs5743618 (G;T) greater resistance to leprosy; but also consequence for Lyme patients. Polymorphisms affecting Toll-like receptor (TLR)-mediated responses could predispose to excessive inflammation during an infection and contribute to an increased risk for poor outcomes in patients with sepsis. Increases susceptibility to death and organ dysfunction. 

(previous four = cytokine explosion!)

rs819147 T/T  Yasko Methylation 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. Individuals with this SNP should consider supplementing their diet with: Ornithine, Molybdenum, Manganese, Zinc, Carnosine and Thiamine (reduced by high sulfates.) Individuals with this SNP are encouraged to avoid Sulfur and Sulfates.

63% chance (higher than average) of docetaxel-induced leukopenia/neutropenia. This creates an intermittent to chronic absence of white blood cells giving susceptibility to bacterial infections.

Late riser. Wakes up 1 hour later than those with AA genotype. Research also suggests, then you while most people are more likely to die shortly before 11am, you are more likely to die later in the day. A common polymorphism near PER1 and the timing of human behavioral rhythms. Study showed that it had influence on wake-up times, as well as time of day that death occurs. Suggests that common (but unidentified) polymorphisms may be associated with a preference for daytime or nighttime activity. rs7221412 appears to sit in a haplotype block and is flanked by rs9914077 and rs2585408 

KELL K/k blood group carrier. As well as Duffy-positive. Might as well get my rH factor done as well to get a full picture of my blood antigens. 

The rs4880(C) allele gives rise to an alanine at this position is it also known as Val16Ala manganese superoxide dismutase, or A16V. Inc risk for mesothemlioma even with no asbestos exposure. Breast cancer carriers being treated with cyclophosphamide had worse survival rates Inc Alzheimer's, noise induced hearing loss, susceptibility to oxidative stress. 

Prone to cluster headaches and migraines. These are also side effects/symptoms to many of the problems I have so is it the genes or a sign of a problem? 

Otitis (middle ear infections), yeah got one rolling right now... for months. 

rs2282679, located in the group-specific component (vitamin D binding protein) GC gene on chromosome 4p12, has been linked by several studies to vitamin D serum concentrations. In both studies, the allele associated with lower vitamin D, and thus the potential for vitamin D insufficiency, is rs2282679(C) 

Neurological:

Rs2237717 has been linked to schizophrenia, ability to recognize facial emotion, and chronic rhinosinusitis, also tumor metastasis. Basically less ability to recognize faces, cancer resistance, chronic sinus problems, and prone to schizophrenia. 

rs6323 (R297R / Arg297Arg) is a SNP in the MAOA (monoamine oxidase A) gene. Monoamine oxidase A degrades serotonin, dopamine, epineprine, and norepinephrine. Seems to be linked with increased anger, schizophrenia, and borderline personality disorder. 

TaqIA (or Taq1A) polymorphism of the dopamine D2 receptor DRD2 gene. is associated with a reduced number of dopamine binding sites in the brain. Plays a role in alcoholism, impulsivity, bad with risk avoidance, addictive behaviors, certain neuropsychiatric disorders. May lead to chronic renal disease and high blood pressure. Slower to recover from brain trauma based on memory and attention tests. Dimminished pleasure response from food. Drug response: ethanol response – Toxicity/ADR. clozapine response – Toxicity/ADR. bupropion response – Efficacy. olanzapine response – Toxicity/ADR. antipsychotics response – Toxicity/ADR. risperidone response - Toxicity/ADR 

rs4680(G) = Warrior. Val, less exploratory, higher COMT enzymatic activity, therefore lower dopamine levels; higher pain threshold, better stress resiliency, albeit with a modest reduction in executive cognition performance under most conditions. A study of the antidepressant paroxetine found  worse effects in Val/Val homozygotes. Seems to be some link with this gene, schizophrenia, and PTSD, I must look further into it. 

oxytocin receptor polymorphism (OXTR) You have a SNP in the oxytocin receptor which may make you less empathetic than most people. When under stress you may have more difficulty recognizing the emotional state of others which impacts loneliness, parenting, and socializing skills.  This also would affect any disease that would feed off of lack of oxytocin or a neurotransmitter that is made off of it. 

You have one short form 5-HTTLPR. You probably have one short-form 5-HTTLPR (serotonin-transporter-linked polymorphic region). Variations in the region have been extensively investigated in connection with neuropsychiatric disorders. 

Resistant to prion diseases, also gives some protection against the other genes that give vulnerability to Alzheimer's. 

Carriers of KIBRA rs17070145 (c:c) have lessened memory capabilities due to differences in hippocampal activities. 

Lower levels of ApoE, seems to indicate increased risk for Alzheimer's. Other genes seems protective against it. I will have to look into what will combat this. 

Associated with PTSD, hyperarousal, impaired fear discrimination in traumatized females, but not males '''Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor.''' 

Several genes for autism and Asperger's, schizophrenia, ADHD, OCD,  bipolar, dyslexia, speech impairment.

Autoimmune risks: 

Hashimoto's (confirmed), Graves, RA (ruled out), PCK (ruled out), Sjögren's syndrome, Lupus (ruled out), MG (ruled out), Crohn's, Celiac, IBS, GB, Ehlers-Danlos syndrome, have genes for MS (but also have a gene that lowers the risk for MS), Parkinson's,  type-1 diabetes, ALS, Ankylosing Spondylitis, Endometriosis,  PCOS (possibly ruled out).

Drug Related: 

Thiopurine methyltransferase deficiency. TPMT gene, potentially encoding a variant incapable of detoxifying byproducts of certain antineoplastic and immunosuppressant drugs.

CYP3A5 non-expressor. As a CYP3A5 non-expressor you are unable to metabolize some common medications. This influences the synthesis of cholesterol, steroids and other lipids. The enzyme metabolizes drugs such as olanzapine, tacrolimus, nifedipine and cyclosporine as well as the steroid hormones testosterone, progesterone and androstenedione. 

CYP3A5*3 homozygote; CYP3A5 non-expressor. Impacts metabolism of tacrolimus, an immunosuppressive drug used in organ transplantation. Drug response sirolimus response – Dosage. cyclosporine response – Dosage. tacrolimus response – Dosage. tacrolimus response due to donor genotype - Dosagetacrolimus response - Efficacy 

NAT2 Rapid metabolizer. NAT2 rapid acetylators can be typically be administered drugs which are substrates of the NAT2 enzyme following standard dosing practices. 

CYP2D6*41 CYP2D6*41 decreased metabolism BUT CYP2D6*2 CYP2D6*2 normal metabolism 

reduced warfarin dose if treated for VTE

Several SNPs in the VKORC1 gene have been linked to warfarin sensitivity, with perhaps the most common being this SNP rs9923231

CYP2C19*17 ultra fast metabolizer; drug metabolism effects; also 0.77x decreased breast cancer risk

rs12248560(T) defines the CYP2C19*17 allele, an ultra fast metabolizer phenotype of the CYP2C19 gene. CYP2C19*17 is likely to lead to less effective drug treatment by, for example, proton pump inhibitors (such as omeprazole) and antidepressants. On the other hand, cancer patients who are CYP2C19*17 carriers are more likely to benefit from tamoxifen treatment, presumably because they break it down more rapidly into the antiestrogenic metabolites endoxifen and 4-hydroxytamoxifen.

CYP2C8 SNP, defining the CYP2C8*3 allele (along with rs10509681). Individuals carrying this SNP may show increased risk of developing acute gastrointestinal bleeding during the use of NSAIDs that are CYP2C8 or CYP2C9 substrates, such as aceclofenac, celecoxib, diclofenac, ibuprofen, indomethazine, lornoxicam, meloxicam, naproxen, piroxicam, tenoxicam and valdecoxib. [PharmGKB:Curated Risk or phenotype-associated allele: A. Phenotype: This variant was associated with increased risk for neurotoxicity with paclitaxel treatment. 

Moderately lower odds of responding to PEG-IFNalpha/RBV treatment for hepatitis C. 

The 'A2' allele of the platelet specific alloantigen system is encoded by rs5918(C), and it has been implicated as increasing the risk of myocardial infarctions, heart disease, and resistance to blood-thinning benefits of aspirin. 

7x more likely to respond to certain antidepressants. This version of a blood brain barrier protein allows many common antidepressants to enter the brain, including: amitriptyline (Elavil), citalopram (Celexa), paroxetine (Paxil), and venlafaxine (Effexor). That makes those antidepressants 7 times more effective. BUT if they are dopamine increasing then this is a toxicity issue due to the genetic low dopamine receptor cites in the brain. 

Increased odds of kidney transplant rejection

Carrier of at least one CYP2D6 variants (non-CYP2D6*1)

rs1135840 (C:G), also known as 4180G>C or S486T, is a SNP in the CYP2D6 gene. Without seeing which two exactly I have, I don't know how well my CYP2D6 metabolizes. This has a lot to do with drug metabolism so I have to dig further into finding out. 

rs1801274  (T:T) Gives slower progression of HIV to AIDS, but higher susceptibility to pneumonia. 

Resistance to malaria. At risk for cancer progression. Cetuximab is more effective against cancer for progressive-free survival. Infliximab is less effective. 

slightly poorer (0.75x) response to metformin in type 2 diabetics s

More likely to gain weight if taking olanzapine. The ancestral allele is C. The rs7412(T) allele, also known as Arg176Cys, generally indicates the presence of an Apoε2 allele; see the ApoE page for a full discussion of the ApoE alleles and their association with Alzheimer's disease. Another SNP related to ApoE is rs429358. In a study of 67 mostly Caucasian patients prescribed the atypical antipsychotic olanzapine, carriers of a rs7412(C) allele were more likely to gain significant weight compared to rs7412(T;T) carriers, as assessed by physiogenomic analysis of corresponding weight profiles.

rs2292954 T variant was associated with toxicity in response to docetaxel and thalidomide.

Penicillin allergy? There are genes for that, and I have them with the allergy. 

Amusing aside: Noticing health genes for Yoruba, Native, Han Chinese, Japanese, Caucasian, Ashkenazim Jewish; all ethnicities I found in a deep genetics scan.