Accurate Education – Genetic Testing: Individual DNA Alleles

Genetic Testing: Individual DNA Alleles

 

DNA testing, performed by obtaining a simple swab of saliva, evaluates an individual’s genetic predisposition to specific traits or characteristics that are inheritable from one’s parents. Genetic test panels consist of multiple individual tests that look at genes associated with these specific traits. The section below explains the implications of individual test findings.

 

 

 See:

Reward Deficiency Syndrome

Genetic Testing: Reward Deficiency Syndrome

See also:

SynaptaGenX

GARS: GeneusHealth.com

Restoregen.com

  

Definitions and Terms Related to Pain

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“Happiness is not something ready made. It comes from your own actions..”

– 14th Dalai Lama

Genetic Testing

Genetic testing is the evaluation 0f DNA and how it affects individual traits. Chromosome are the genetic material inherited from one’s parents in two copies, with one copy inherited from each parent. Chromosomes are made up of millions of genes made up of DNA, with each gene occupying a specific location on a chromosome. Genes represent a unit of hereditary information that are responsible for the transmission of inherited traits.  When the copies of a gene differ from one other, they are known as alleles or variant forms of a gene. Alleles code for the transmission of traits such as the color of one’s eyes or the susceptibility to a medical condition. Genetic science is exploring how specific individual alleles are associated with specific traits or characteristics of a person.

 

Individual DNA Alleles – Their Behavior & Predisposition Risks

GARS Panel (Genetic Addiction Risk Score®)

The Genetic Addiction Risk Score (GARS®) is a panel of genetic tests that evaluates risk for Reward Deficiency Syndrome (RDS), the underlying condition that predisposes individuals to chemical and behavioral addictions as well as disorders such as PTSD,  ADHD, Tics, Tourette Syndrome, autism, Asperger Syndrome, OCD, “compulsive” sexual practices, binge eating and others. For example, Patients that carry four or more of any risk allele in the GARS panel predict severity of drug abuse (including opioids), whereas carrying seven or more risk alleles of GARS specifically predicts alcohol abuse severity. The GARS® is the first useful tool in understanding an individual’s specific vulnerability to RDS and addiction that allows for personalized nutrition-based intervention for treatment.

 
 
The following is a list of the ten individual tests that make up the GARS® panel and the RDS risks associated with each specific genetic variant allele:

COMT – G Allele

Substance Abuse/Addiction: Opioids, Alcohol, Cannabis, Glucose, Stimulants (Cocaine), Nicotine
Non-Substance Behaviors: ADD/ADHD, Oppositional Defiant, Pathological Aggression, Panic Disorder, Anxiety, OCD, Internet Gaming

High COMT activity
An increased rate of synaptic DA breakdown due to having high catabolic genotype of the COMT gene.

 
Low COMT activity
Slower breakdown of DA due to polymorphisms in both the MOA and or COMT may lead to hyperactivity as seen in Attention Deficit Hyperactivity Disorder (ADHD).

 

DRD1 – A Allele

Substance Abuse/Addiction: Alcohol & Nicotine
Non-Substance Behaviors: Novelty Seeking

 

DRD2 – A1 Allele

Over 100 million people in the United States alone carries this gene form. Genetic variations of this A1 form of the dopamine D2 receptor gene are associated with 30-40 % less D2 receptors.

Substance Abuse/Addiction: Opioids, Heroin, Alcohol, Cannabis, Glucose, Cocaine, Nicotine
Non-Substance Behaviors: ADD/ADHD, Conduct Disorder, Gambling Disorder, Internet Gambling, Hypersexuality Disorder, Novelty Seeking, Pathological Aggression, PTSD

 

Dopamine D2 receptors and Opioid Addiction
Individuals carrying D2 TaqA1 vs A2 alleles are at increased risk for Reward Deficiency Syndrome (RDS), the underlying condition associated with substance and behavioral addictions.  The D2 TaqA1 allele is associated with stronger cue-elicited heroin craving and an increased risk for addiction relapse in the treatment for heroin abuse, suggesting a pharmacogenetic approach to the treatment of opioid addiction.  Constant, mild stimulation of the DA receptor system with low doses of a D2 agonist results in significant proliferation of D2 receptors, in spite of genetic variants. This proliferation of D2 receptors allows for improved dopamine balance in the reward center of the brain, the nucleus accumbens (NAc), leading to reduced cravings and relapse.  Studies also suggest that increasing DRD2 receptors induces a significant reduction in both alcohol and cocaine cravings as well.

See: Reward Deficiency Syndrome (RDS) & Addiction

 

Dopamine D2 Receptors and Chronic Pain
Dopamine is required for proper pain sensitivity and tolerance. Most opiates work via dopamine to reduce pain. DA is also the anti-stress molecule.

 

Changes in synaptic dopamine neurotransmission in the reward centers of the brain are thought to play a role in chronic pain. Dopamine D2 receptors play an inhibitory role in persistent pain. Low or hypodopaminergic function in the brain may predispose individuals to low pain tolerance. Carriers of the D2 TaqA1 allele is found in reward deficiency syndrome (RDS) conditions and individuals with D2 TaqA1 variant allele are good candidates for nutrients designed to enhance dopamine release in the brain.

See: Reward Deficiency Syndrome (RDS) & Chronic Pain

 

 

DRD3 – C Allele

Substance Abuse/Addiction: Glucose, Cocaine
Non-Substance Behaviors: ADD/ADHD, OCD, Pathologic Aggression

 

DRD4 – C allele

Substance Abuse/Addiction: Opioids, Alcohol, Cannabis, Glucose, Nicotine
Non-Substance Behaviors: ADD/ADHD, Novelty Seeking, Conduct Disorder, Hypersexuality Disorder, Pathological Aggression

 

DAT1 – 9R Allele

Substance Abuse/Addiction: Heroin, Alcohol, Cocaine, Nicotine
Non-Substance Behaviors: ADD/ADHD, Depression (Anhedonia), PTSD

 

In the case of DAT1, genotype 9/9 was associated with early opiate addiction. The combination of hSERT genotype 10/10 with DAT1 genotype 10/10 was shown to be a risk factor of opiate abuse under 16 years of age.

 

OPRM1 – G Allele

Substance Abuse/Addiction: Opioids, Alcohol, Glucose, Cocaine, Nicotine
Non-Substance Behaviors: Overeating, Stress PTSD

 

OPRM1 and Chronic Pain

Variants of the OPRM1 gene may affect an individuals pain sensitivity and pain tolerance. The G allele single nucleotide polymorphism A118G of the OPRM1 gene is associated with decreased potency of morphine (and its metabolite, morphine-6-glucuronide), and with decreased analgesic effects and higher alfentanil dose requirements. OPRM1 variants may explain why some patients need higher opioid doses and why some patients experience more adverse effects. Pharmacogenetic testing may facilitate individualized opioid therapy.

 

5HTTLPR – S or LG Allele

Substance Abuse/Addiction: Opioids, Alcohol, Cannabis, Glucose, Cocaine, Nicotine
Non-Substance Behaviors: ADD/ADHD,PTSD, Pathological Aggression

 

MAOA – 4R Allele

Substance Abuse/Addiction: Opioids, Alcohol, Glucose, Nicotine
Non-Substance Behaviors: ADD/ADHD,Harm Avoidance, Novelty Seeking

 

High MOA activity
An increased rate of mitochondrial DA breakdown, due to having high MOA activity or an increased rate of synaptic DA breakdown due to having high catabolic genotype of the COMT gene. However, slower breakdown of DA due to polymorphisms in both the MOA and or COMT may lead to hyperactivity as seen in Attention Deficit Hyperactivity Disorder (ADHD).

 

GABR3 – Over-expressed 181 Allele

Substance Abuse/Addiction: Alcohol
Non-Substance Behaviors: PTSD

 

Other Individual Alleles

 

Genetics of Pain

Certain genes have been identified to play a role in pain sensitivity and analgesic requirements in the treatment of acute and chronic pain,  including catechol-O-methyl- transferase (COMT), melanocortin-1 receptor, guanosine triphosphate cyclohydrolase, and mu-opioid receptor (OPRM1). Genetics of the dopamine system in the brain play a crucial role in pain.

See: Reward Deficiency Syndrome (RDS) & Chronic Pain

 

Genetics of the Cytochrome P450 (CYP-450) Enzymes

Genetic variants of drug-metabolizing enzymes impact the response to medications is generally well described, including the cytochrome P450 (CYP-450) enzymes. Genetic variants (polymorphisms) of the CYP-450 enzymes impact the effectiveness of codeine, tramadol, tricyclic antidepressants and nonsteroidal-antiinflammatory drugs (NSAIDs). Additionally, genetic variants contribute to drug interactions by enhancing or reducing their metabolism.

 

CYP 2B6
The CYP2B6 enzyme contributes to the breakdown of methadone and genetic variants associated with reduced activity of CYP2D6 can result in increased cardiac toxicity related to the use of methadone.

 

CYP) 2C9

The CYP) 2C9 enzymes are associated with the breakdown of nonsteroidal-antiinflammatory drugs (NSAIDs). Genetic variants of this enzyme can reduce metabolism of NSAIDs which may lead to increased toxicity and frequency of side effects.

 

CYP) 2C19

The CYP) 2C19 enzymes are associated with the metabolism of many antidepressant medications. Genetic variants of this enzyme can affect metabolism of these medications which may lead to increased toxicity and frequency of side effects as well as impacting their effectiveness.

 

CYP 2D6
Genetic variants associated with inactivity of cytochrome P450 (CYP) 2D6 is associated with ineffectiveness of codeine and reduced effectiveness of tramadol for pain due to impaired metabolism of the parent drugs to active metabolites.

 

Genetics of the MDR1 (also referred to as the ABCB1 gene)

MDR1 receptor mutations can affect the efficiency of the transport of drugs, especially opioids, from the gut and the central nervous system to the blood stream with signficant consequences. Variations in the transport of opioids can impact their analgesic effectiveness and dosing requirements.

 

Genetics of PENK
PENK genetics impacts the body’s manufacturing of enkephalins, the endogenous opioids and can affect pain sensitivity and intolerance.

 

Genetics of TNF-a
Genetics of TNF-a affects inflammatory processes and variants may result in the need for increased dosing of NSAIDs.

 

Genetics of Pain Medications

Morphine
Animal research indicates that both sensitivity and tolerance to morphine are genotype-dependent, and their inheritance is characterized by dominance or partial dominance. Further research is needed to identify the potential usefulness of this for pain management in humans.

 

Methadone
Methadone dosage is individualized and highly variable in the management of both pain and opioid addiction. Methadone is a substrate for the P-glycoprotein transporter, encoded by the MDR (ABCB1) gene, which regulates central nervous system exposure to methadone. ABCB1 genetic variability influences daily methadone dose requirements; individuals carrying two copies of the wild-type variant allele require higher doses compared with those with one copy and those with no copies.

 

 

 

Resources:

  1. GARS: GeneusHealth.com
  2. Restoregen.com
  3. SynaptaGenX

 

RDS – Overview

  1. The Addictive Brain – All Roads Lead to Dopamine – 2012
  2. Hatching the behavioral addiction egg – Reward Deficiency Solution System – 2014
  3. Sex, Drugs, and Rock ‘N’ Roll – Hypothesizing Common Mesolimbic Activation as a Function of Reward Gene Polymorphisms – 2012
  4. “Dopamine homeostasis” requires balanced polypharmacy – Issue with destructive, powerful dopamine agents to combat America’s drug epidemic
  5. Neurodynamics of relapse prevention-neuronutrient approach to outpatient DUI offenders
  6. Genetic Addiction Risk Testing Coupled with Pro Dopamine Homeostasis
  7. Pro-dopamine regulator, KB220Z, attenuates hoarding and shopping behavior in a female, diagnosed with SUD and ADHD
  8. Neuro-Nutrient Effects on Weight Loss in Carbohydrate Bingers – an open clinical trial
  9. Enkephalinase Inhibition – Regulation of Ethanol Intake in Genetically Predisposed Mice
  10. The D2 dopamine receptor gene as a determinant of reward deficiency syndrome – 1996
  11. Dopamine D2 receptor gene variants: association and linkage studies in impulsive-addictive-compulsive behaviour. – PubMed – NCBI
  12. Activation instead of blocking mesolimbic dopaminergic reward circuitry is a preferred modality in the long term treatment of reward deficiency syndrome (RDS) – a commentary – 2008
  13. Reward deficiency syndrome: a biogenetic model for the diagnosis and treatment of impulsive, addictive, and compulsive behaviors. – PubMed – NCBI
  14. Association of polymorphisms of dopamine D2 receptor (DRD2), and dopamine transporter (DAT1) genes with schizoid:avoidant behaviors (SAB). – PubMed – NCBI
  15. Reward deficiency syndrome: genetic aspects of behavioral disorders. – PubMed – NCBI
  16. The D2 dopamine receptor gene as a predictor of compulsive disease: Bayes’ theorem. – PubMed – NCBI
  17. Delayed P300 latency correlates with abnormal Test of Variables of Attention (TOVA) in adults and predicts early cognitive decline in a clinical se… – PubMed – NCBI

 

RDS – ADD

  1. Attention-deficit-hyperactivity disorder and reward deficiency syndrome – 2008
  2. Reward Deficiency Syndrome – Attentional Arousal Subtypes, Limitations of Current Diagnostic Nosology, and Future Research – 2015
  3. Neurogenetic interactions and aberrant behavioral co-morbidity of attention deficit hyperactivity disorder (ADHD) -dispelling myths – 2005
  4. Epigenetics in Developmental Disorder – ADHD and Endophenotypes
  5. Low Dopamine Function in Attention Deficit:Hyperactivity Disorder – Should Genotyping Signify Early Diagnosis in Children? – 2014
  6. Enhancement of attention processing by Kantroll in healthy humans: a pilot study. – PubMed – NCBI
  7. Pro-dopamine regulator, KB220Z, attenuates hoarding and shopping behavior in a female, diagnosed with SUD and ADHD

 

RDS – Gaming

  1. linking-online-gaming-and-addictive-behavior-converging-evidence-for-a-general-reward-deficiency-in-frequent-online-gamers-2014

 

RDS – Genetics

  1. Multilocus Genetic Composite Reflecting Dopamine Signaling Capacity Predicts Reward Circuitry Responsivity 2012
  2. Genetic Addiction Risk Score (GARS) – Testing For Polygenetic Predisposition and Risk to Reward Deficiency Syndrome (RDS) – 2011
  3. Neurogenetic Impairments of Brain Reward Circuitry Links to Reward Deficiency Syndrome (RDS) – Potential Nutrigenomic Induced Dopaminergic Activation

 

RDS – Obesity

  1. Reward Deficiency Syndrome Studies of KB220 Variants
  2. Mood, food, and obesity
  3. Dopamine and glucose, obesity, and reward deficiency syndrome – 2014
  4. Dopamine for “wanting” and opioids for “liking”: a comparison of obese adults with and without binge eating. – PubMed – NCBI
  5. “Liking” and “Wanting” Linked to Reward Deficiency Syndrome (RDS) – Hypothesizing Differential Responsivity in Brain Reward Circuitry – 2012
  6. Neuro-Genetics of Reward Deficiency Syndrome (RDS) as the Root Cause of “Addiction Transfer”- 2011

 

RDS – Chronic Pain

  1. Hypothesizing that brain reward circuitry genes are genetic antecedents of pain sensitivity and critical diagnostic and pharmacogenomic – 2009
  2. A Multi-Locus Approach to Treating Fibromyalgia by Boosting Dopaminergic Activity in the Meso-Limbic System of the Brain – 2014

 

RDS – PTSD

  1. Neuro-psychopharmacogenetics and Neurological Antecedents of Posttraumatic Stress Disorder – Unlocking the Mysteries of Resilience and Vulnerability – 2010
  2. Diagnosis and Healing In Veterans Suspected of Suffering from Post-Traumatic Stress Disorder (PTSD) Using Reward Gene Testing and RewardCircuitry Natural Dopaminergic Activation-2012
  3. Putative dopamine agonist (KB220Z) attenuates lucid nightmares in PTSD patients – Role of enhanced brain reward functional connectivity and homeostasis redeeming joy – 2015

 

RDS – Sleep

  1. Dopaminergic Neurogenetics of Sleep Disorders in Reward Deficiency Syndrome (RDS) – 2014

 

RDS – Treatment

RDS Treatment Overview

  1. Clinically Combating Reward Deficiency Syndrome (RDS) with Dopamine Agonist Therapy as a Paradigm Shift – Dopamine for Dinner? 2015
  2. Neurogenetics and Nutrigenomics of Neuro-Nutrient Therapy for Reward Deficiency Syndrome (RDS)

 

RDS Treatment – Meditation

  1. Increased dopamine tone during meditation-induced change of conscio… – PubMed – NCBI

 

RDS Treatment – Music Therapy

  1. Do dopaminergic gene polymorphisms affect mesolimbic reward activat… – PubMed – NCBI

 

RDS Treatment – SynaptaGenX

SynaptaGenX – Overviews

  1. Synaptamine – brief summary

 

SynaptaGenX – Buptrenorphine

  1. Withdrawal from Buprenorphine:Naloxone and Maintenance with a Natural Dopaminergic Agonist – A Cautionary Note

 

SynaptaGenX – Fibromyalgia

  1. A Multi-Locus Approach to Treating Fibromyalgia by Boosting Dopaminergic Activity in the Meso-Limbic System of the Brain

 

SynaptaGenX – Lucid Nightmares

  1. Putative dopamine agonist (KB220Z) attenuates lucid nightmares in PTSD patients – Role of enhanced brain reward functional connectivity and homeostasis redeeming joy – 2015
  2. Using the Neuroadaptagen KB200zTM to Ameliorate Terrifying, Lucid Nightmares in RDS Patients – the Role of Enhanced, Brain- Reward, Functional Connectivity and Dopaminergic Homeostasis – 2015

 

SynaptaGenX – PTSD

  1. Putative dopamine agonist (KB220Z) attenuates lucid nightmares in PTSD patients – Role of enhanced brain reward functional connectivity and homeostasis redeeming joy – 2015
  2. Diagnosis and Healing In Veterans Suspected of Suffering from Post-Traumatic Stress Disorder (PTSD) Using Reward Gene Testing and RewardCircuitry Natural Dopaminergic Activation-2012

 

SynaptaGenX – Sleep

  1. hypothesizing-that-putative-dopaminergic-melatonin-benzodiazepine-reward-circuitry-receptors – 2013

Emphasis on Education

 

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