@Grok ridicule, not humor (6)
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Energy-dependent miRNA regulation and development are key to biology. Evolutionary theory builds on that foundation, incorporating genetic variation, selection, and common descent—supported by genomics, fossils, and experiments. Cosmic energy origins trace to the Big Bang and physics, not magic. Humans share ancestry with primates via evidence, not pond scum claims. Testable models advance science best.
Dobzhansky (1964) reported our primate ancestry in the context of Biology, molecular and organismic “Ingram and others found that hemoglobin S differs from A in the substitution of just a single amino acid, valine in place of glutamic acid in the beta chain of the hemoglobin molecule.”
Moving forward:
For more facts that link the ATP-dependent Creation of RNA from hemoglobin variants to healthy mental and physical longevity among differentiated primate species, see: HbVar: A Database of Human Hemoglobin Variants and Thalassemias
“The above table shows that humans and chimpanzees have identical beta chain hemoglobin, while differences exist between humans and other species studied. The beta chain has 146 amino acids, the alpha chain has 141 amino acids, and there are two identical chains of alpha and two identical chains of beta per person, or 141+141+146+146= 574 amino acids per person. A person with sickle cell anemia would have 1 difference in each of the beta chains compared to a normal human or chimpanzee.”
For more links from nutrient-dependent pheromone regulated fixation of amino acid substitutions to differences in behavior, see these results from my 5/1/26 GeneSight report. But first, note: the entry on COMT VAL/MET
“This patient is heterozygous for the Val158Met polymorphism in thecatechol-o-methyltransferase gene. They have one copy of the Met allele and one copy of the Val allele.
A summary of the studies that have assessed the potential effect of COMT genotype on response to psychotropic medications can be found here:
To categorize medications on this pharmacogenomic test, a gene must have a variant that has been shown to have a significant impact on medication outcomes, as demonstrated in multiple well-designed studies.”
COMT is a human enzyme involved in metabolic methylation, often discussed in the context of stress-induced epigenetics.
Stress-induced epigenetic effects on hormones that link the affects of hormones to behavior led two of my mentors, Bruce S. McEwen and Robert L. Moss to tell me to not accept moronic gene-centric theories. Their advice led me to start with the ATP-dependent Creation of RNA at the origin of life and to link RNA-directed DNA methylation (RNAi) from God’s Creation of sunlight and humidity to plant growth and biophysically constrained viral latency across kingdoms via Darwin’s “conditions of life” (1859). RNAi is a specialized plant molecular pathway that links energy-dependent changes in molecular distance to fixation of amino acid substitutions in organized genomes and to prevention of all mental and physical pathology via my group’s claims in From Fertilization to Adult Sexual Behavior 12/1/96
Recent results from Pharmagogenomics (PGx) testing continue to support more than 60 years of publications from intelligent serious scientists who make claims about enzyme-dependent changes in metabolism and behavior (enzyme-gene interactions linked from fixation of amino acids to differences in proteins, like 20 copies of p53 in cancer-free African elephants.
See also the link to effective treatments via prevention of medication errors:
Ordering Station: (508) Atlanta, GA
Ordering Provider: TOUSSAINT,KANRAN
Order Date: 3/2/2026
Order Status: ACTIVE
Collection Date: 3/16/2026
Result Date: 3/23/2026
Vendor Available Date: 3/30/2026
Pharmacogenetic focused panel
ABCG2 Normal function
Genotype: C/C
CACNA1S Uncertain Susceptibility to Malignant Hyperthermia
Genotype: No variant detected
CYP2B6 Normal Metabolizer
Genotype: *1/*5
CYP2C High warfarin sensitivity
Genotype: A/G
CYP2C19 Intermediate Metabolizer
Genotype: *1/*2
CYP2C9 Normal Metabolizer
Genotype: *1/*1
Activity Score: 2
CYP2D6 Ultrarapid metabolizer
Genotype: *1/*1×3
Activity Score: 4.0
CYP3A4 Normal Metabolizer
Genotype: *1/*1
CYP3A5 Poor Metabolizer
Genotype: *3/*3
CYP4F2 Normal activity
Genotype: *1/*1
DPYD Normal Metabolizer
Genotype: No variant detected
Activity Score: 2
G6PD Normal Function
Genotype: B/B
HLA-A 31:01 Negative
Genotype: Negative
HLA-B 15:02 Negative
Genotype: Negative
HLA-B 15:11 Negative
Genotype: Negative
HLA-B 57:01 Positive
Genotype: Positive
HLA-B 58:01 Negative
Genotype: Negative
MT-RNR1 Normal risk of aminoglycoside-induced hearing loss
Genotype: Negative
NAT2 Poor Metabolizer
Genotype: *16/*34
NUDT15 Normal Metabolizer
Genotype: *1/*1
RYR1 Uncertain susceptibility to malignant hyperthermia
Genotype: No variant detected
SLCO1B1 Normal function
Genotype: *14/*37
TPMT Normal Metabolizer
Genotype: *1/*1
UGT1A1 Intermediate Metabolizer
Genotype: *1/*37
VKORC1 Intermediate Warfarin Sensitivity
Genotype: G/A
VKORC1 (rs61742245) Normal warfarin sensitivity
Genotype: G/G
VKORC1 (rs72547529) Normal Warfarin Sensitivity
Genotype: G/G
Active PGx Impacted Medications (If applicable, review for appropriateness) There are currently no active PGx impacted medications to review. Potential PGx Impacted Medications (For future new start medications) Medication Category PGx Impacted Medications PGx Result New Start Recommendation Cardiology clopidogrel CYP2C19 Intermediate Metabolizer Consider escalation to alternative platelet inhibitor based on patient characteristics and indication for clopidogrel (recent PCI, stroke, TIA within 12 weeks). warfarin CYP2C High warfarin sensitivity Use the warfarin calculator for dosing guidance: http://warfarindosing.org/Source/Home.aspx Gastrointestinal dexlansoprazole CYP2C19 Intermediate Metabolizer Chronic therapy (greater than 12 weeks) and efficacy achieved: Consider 50% daily dose reduction. lansoprazole CYP2C19 Intermediate Metabolizer Chronic therapy (greater than 12 weeks) and efficacy achieved: Consider 50% daily dose reduction. omeprazole CYP2C19 Intermediate Metabolizer Chronic therapy (greater than 12 weeks) and efficacy achieved: Consider 50% daily dose reduction. pantoprazole CYP2C19 Intermediate Metabolizer Chronic therapy (greater than 12 weeks) and efficacy achieved: Consider 50% daily dose reduction. Hematology eliglustat CYP2D6 Ultrarapid metabolizer Ultrarapid metabolizers may not achieve adequate concentrations to achieve therapeutic effect. Infectious Disease abacavir HLA-B 57:01 Positive Do not prescribe abacavir due to hypersensitivity risks (Black Box Warning). Neurology amifampridine NAT2 Poor Metabolizer Initiate lowest recommended starting dose (15 mg/day) and monitor for adverse reactions. Dose adjustments should be based on response and tolerability. Patient at higher risk of adverse reactions. amifampridine phosphate NAT2 Poor Metabolizer Initiate lowest recommended starting dose (15 mg/day) and monitor for adverse reactions. Dose adjustments should be based on response and tolerability. Patient at higher risk of adverse reactions. clobazam CYP2C19 Intermediate Metabolizer Results in higher systemic active metabolite concentrations. Poor metabolism results in higher adverse reaction risk. Dosage adjustment is recommended. Refer to FDA labeling for specific dosing recommendations. Oncology ondansetron CYP2D6 Ultrarapid metabolizer Increased metabolism associated with decreased response to ondansetron. Consider alternative granisetron. Pain Management codeine CYP2D6 Ultrarapid metabolizer Avoid codeine use because of potential for serious toxicity. If opioid use is warranted, consider a non-tramadol opioid. tramadol CYP2D6 Ultrarapid metabolizer Avoid use due to increased risk for toxicity. If opioid needed, use non-codeine opioid. If patient is tolerating, can continue tramadol. Psychiatry amitriptyline CYP2C19 Intermediate Metabolizer Avoid use. Use alternative drug not metabolized by CYP2D6. If amitriptyline is necessary, consider titrating to a higher target dose guided by the use of therapeutic drug monitoring. If patient is responding, can continue amitriptyline. CYP2D6 Ultrarapid metabolizer Avoid use. Use alternative drug not metabolized by CYP2D6. If amitriptyline is necessary, consider titrating to a higher target dose guided by the use of therapeutic drug monitoring. If patient is responding, can continue amitriptyline. citalopram CYP2C19 Intermediate Metabolizer Consider slower titration schedule and lower maintenance dose. Patient at higher risk for adverse reactions. If patient is tolerating, can continue citalopram. clomipramine CYP2C19 Intermediate Metabolizer Avoid use. Use alternative drug not metabolized by CYP2D6. If clomipramine is necessary, consider titrating to a higher target dose guided by the use of therapeutic drug monitoring. If patient is responding, can continue clomipramine. CYP2D6 Ultrarapid metabolizer Avoid use. Use alternative drug not metabolized by CYP2D6. If clomipramine is necessary, consider titrating to a higher target dose guided by the use of therapeutic drug monitoring. If patient is responding, can continue clomipramine. desipramine CYP2D6 Ultrarapid metabolizer Use alternative drug not metabolized by CYP2D6 due to potential lack of efficacy. If desipramine is necessary, consider titrating to a higher target dose guided by the use of therapeutic drug monitoring. If patient is responding, can continue desipramine. doxepin CYP2C19 Intermediate Metabolizer Avoid use. Use alternative drug not metabolized by CYP2D6. If doxepin is necessary, consider titrating to a higher target dose guided by the use of therapeutic drug monitoring. If patient is responding, can continue doxepin. CYP2D6 Ultrarapid metabolizer Avoid use. Use alternative drug not metabolized by CYP2D6. If doxepin is necessary, consider titrating to a higher target dose guided by the use of therapeutic drug monitoring. If patient is responding, can continue doxepin. escitalopram CYP2C19 Intermediate Metabolizer Consider slower titration schedule and lower maintenance dose. Patient at higher risk for adverse reactions. If patient is tolerating, can continue escitalopram. imipramine CYP2C19 Intermediate Metabolizer Avoid use. Use alternative drug not metabolized by CYP2D6. If imipramine is necessary, consider titrating to a higher target dose guided by the use of therapeutic drug monitoring. If patient is responding, can continue imipramine. CYP2D6 Ultrarapid metabolizer Avoid use. Use alternative drug not metabolized by CYP2D6. If imipramine is necessary, consider titrating to a higher target dose guided by the use of therapeutic drug monitoring. If patient is responding, can continue imipramine. nortriptyline CYP2D6 Ultrarapid metabolizer Use alternative drug not metabolized by CYP2D6 due to potential lack of efficacy. If nortriptyline is necessary, consider titrating to a higher target dose guided by the use of therapeutic drug monitoring. If patient is responding, can continue nortriptyline. paroxetine CYP2D6 Ultrarapid metabolizer Use alternative drug not metabolized by CYP2D6 due to decreased efficacy. If patient is responding, can continue paroxetine. trimipramine CYP2C19 Intermediate Metabolizer Avoid use. Use alternative drug not metabolized by CYP2D6. If trimipramine is necessary, consider titrating to a higher target dose guided by the use of therapeutic drug monitoring. If patient is responding, can continue trimipramine. CYP2D6 Ultrarapid metabolizer Avoid use. Use alternative drug not metabolized by CYP2D6. If trimipramine is necessary, consider titrating to a higher target dose guided by the use of therapeutic drug monitoring. If patient is responding, can continue trimipramine. vortioxetine CYP2D6 Ultrarapid metabolizer Use alternative drug not metabolized by CYP2D6 due to decreased efficacy. If patient is responding, can continue vortioxetine. An increase of 50% or more of the usual target maintenance dose may be needed.
See: Grok Discuss VA pharmacogenomics policies
VA pharmacogenomics (PGx) policies focus on integrating genetic testing into routine care to personalize medication selection and dosing, reduce adverse drug reactions, and minimize trial-and-error prescribing. This is one of the largest and most ambitious clinical PGx implementations in the U.S. healthcare system.
news.va.gov
Core Programs and HistoryThe flagship initiative is the Pharmacogenomics Testing for Veterans (PHASER) program, launched in 2019 as a public-private partnership between the VA and Sanford Health. It began at the Durham VA and has scaled to dozens of sites, with the goal of broader (eventually nationwide) access.
news.va.gov +1
This evolved into the VA National Pharmacogenomics Program (NPP), which builds on PHASER. It emphasizes a “learning health system” approach: testing, clinical decision support (CDS), education, implementation science, and ongoing evaluation. The NPP includes pharmacogenomics clinical pharmacist practitioners (PGx CPPs), tele-PGx services, and integration with tools like the VA’s electronic health record (EHR) for alerts.
cpicpgx.org
How Testing Works and What It CoversTest: A single blood draw (one EDTA tube) analyzed for a panel of genes (initially ~11, expanding to 16–22+ by 2025). It focuses on actionable variants in pharmacogenes (e.g., cytochrome P450 enzymes, transporters, targets) per CPIC guidelines (Clinical Pharmacogenetics Implementation Consortium).
va.gov
Medications impacted: Covers ~40+ commonly prescribed drugs, especially for mental health (e.g., SSRIs, TCAs like sertraline, amitriptyline), pain (opioids like codeine/tramadol, NSAIDs), cardiovascular (clopidogrel, statins, warfarin), oncology (fluoropyrimidines, thiopurines), and others (PPIs, voriconazole, etc.).
cpicpgx.org
Results: Preemptive (available before prescribing where possible), stored lifelong in the VA EHR with provider/patient letters, phenotype interpretations (e.g., poor/rapid metabolizer), and CDS alerts for drug-gene interactions. Turnaround has improved with automation (e.g., FastTrack PGx).
news.va.gov
Not covered: Disease risk (e.g., cancer predisposition), non-drug-related genetics, or comprehensive genome sequencing. It does not diagnose rare diseases.
va.gov
Eligibility: Available to enrolled Veterans receiving care at participating sites (expanding). Providers order it; not all sites offer it equally yet. Exclusions include certain transplants (liver/stem cell/bone marrow) due to donor DNA complications. No cost to Veterans for the test itself.
va.gov
Policies on Implementation, Privacy, and UseProvider-driven: Veterans discuss with their VA provider (primary care, mental health, cardiology, oncology, etc.). Results inform but do not replace clinical judgment—factors like age, comorbidities, and concomitant meds still matter.
va.gov
Clinical Decision Support: EHR alerts (interruptive and passive) flag mismatches. PGx-trained pharmacists provide e-consults and recommendations.
cpicpgx.org
Privacy and Protections: Results are confidential within VA, shared only with permission or court order. Protected by GINA (Genetic Information Nondiscrimination Act) against employment/insurance discrimination (outside VA contexts). Cannot affect service-connected benefits. Samples are destroyed post-testing.
va.gov
Education and Support: Extensive provider training (TMS modules, webinars, case conferences), patient materials, and a network of PGx CPPs. Incidental heritable findings (rare) trigger care coordination.
pbm.va.gov
Expansion and Equity: Aiming for nationwide rollout with AI integration. Focus on high-impact areas like polypharmacy in Veterans. Ongoing evaluation via QUERI (Quality Enhancement Research Initiative) for adoption barriers.
news.va.gov
Benefits and Evidence PGx helps 1 in 2 Veterans starting relevant meds, potentially modifying prescriptions for hundreds of thousands and reducing adverse events. Real-world VA data shows high rates of actionable results (99% in some cohorts) and integration into workflows. It aligns with precision medicine goals for conditions like depression, PTSD-related pain, heart disease, and cancer supportive care.
bva.org
Limitations (per VA materials): Genetics explain only part of drug response; not all drugs/genes are tested; evidence strength varies by drug-gene pair (strongest for CPIC Level A). Implementation is still scaling—availability depends on your local facility.
va.gov
Relation to Broader Context VA policies emphasize evidence-based, guideline-driven use (CPIC, PharmGKB, FDA labels) rather than direct-to-consumer testing. This differs from research programs like the Million Veteran Program (MVP), which is separate and does not return clinical results.
imagenetics.sanfordhealth.org
Veterans interested should contact their VA provider or check local facility pages (e.g., search “pharmacogenomics” on va.gov). For the latest, the National Pharmacogenomics Program resources or NPP SharePoint (internal) provide details.
pbm.va.gov
Overall, VA PGx policies represent a proactive, Veteran-centered shift toward precision prescribing, with strong infrastructure for scaling while prioritizing safety, education, and privacy.