DNA

Assessing Risk for Autism: A Brand New Study and Test from GPL

MattBlogPic.png

Welcome back to the GPL blog.  I have an exciting announcement: We (GPL) recently conducted a study, and the results demonstrate that the gene ARHGEF6 may play a role in the development of autism.  In the individuals we genotyped, we found that males that had a mutation in this gene are predisposed to develop autism.  Because of this important finding, GPL is now testing for mutations to the ARHGEF6 gene.  Information about this test, the Autism Risk Assessment, including the downloadable brochure can be found here

If you’re a physician with a specialty in pediatric special needs (MD, DO, ND, PA, or NP only) and you’re interested in joining our referral list for ordering and interpreting this new test, please contact your assigned GPL sales representative, send an e-mail to sales@gpl4u.com, or call the lab at (913) 341-8949.

Blog1.png

The Study:

This study was published in the journal, Hereditary Genetics and can be found online here

The Great Plains Laboratory organized the study utilizing volunteers as well as patient samples from the Autism Genetic Resource Exchange (AGRE), which is a program funded by Autism Speaks. In the study, the researchers genotyped 252 single nucleotide polymorphisms (SNPs) in 35 different genes that had previously been identified as autism risk candidate genes. This study was performed with 247 controls (106 male and 141 female) and 155 patients on the autistic spectrum (134 male and 21 female). They found the most significant marker for autism of the 252 SNPs tested was a genetic variation called rs2295868 in the ARHGEF6 gene on the X chromosome. The odds ratio for males with this SNP was 4.09 with a p value <0.0003, which means nearly 80% would likely develop autism at some point in their lives.  This is higher than any other single SNP previously evaluated for autism risk.  The odds ratio for females (1.02) for the same SNP was not statistically significant and did not indicate that this SNP increased the risk of autism for females.

Blog2.png

Since the ARHGEF6 gene is on the X chromosome, this research helps to explain the excess ratio of autism in males, such that males are 4.5 times more affected with autism than females. Males receive an X chromosome only from their mothers while females receive an X chromosome from both their fathers and mothers. Thus, mothers will transmit the affected gene to their sons while both mother and father may transmit the affected gene to their daughters. However, 20% of males with the affected gene do not appear to develop autism, although they may be at risk for schizophrenia and inflammatory bowel disorders. The ARHGEF6 gene SNP was found in 30% of the males with autism spectrum disorders meaning that 70% of cases of autism spectrum disorder in males are due to other causes. A negative result for the ARHGEF6 gene SNP does not rule out a child developing autism from other genes or other non-genetic causes.

 
Blog3.png
 

Below are some commonly asked questions about the ARHGEF6 gene, along with answers.  If you’re not able to find the answer to your specific question(s) here, please send an e-mail to autismrisk@gpl4u.com and either I or one of our other experts will respond to you as soon as possible.

HOW DO I ORDER THE ARHGEF6 TEST?

This test is offered exclusively from The Great Plains Laboratory, Inc.  Tests can be ordered through physicians (MD, DO, ND, PA, or NP only) or certified genetic counselors. 

GPL will be building a referral database of physicians who can order and interpret this test.  In the meantime, to find a pediatric special needs physician in your area, visit the Medical Academy of Pediatric Special Needs (MAPS) web site, https://www.medmaps.org/clinician-directory/ to find member physicians by state.  Please note these physicians are not guaranteed to be able to order this test.  Physicians will also have their own fees for ordering and interpreting tests.  Please contact them to inquire about fees.

This test is not available in the state of New York. 

I AM A PEDIATRIC SPECIAL NEEDS PHYSICIAN AND I’M INTERESTED IN JOINING THE REFERRAL LIST FOR TEST ORDERING AND INTERPRETATION.  HOW DO I JOIN?

Please contact your assigned GPL sales representative, send an e-mail to sales@gpl4u.com, or call the lab at (913) 341-8949.

HOW DO I FIND A GENETIC COUNSELOR?

You may seek a genetic counselor through the National Society of Genetic Counselors at www.nsgc.org or through the American Board of Genetic Counseling at www.abgc.net.

Blog4.png

WHAT IS THE ARHGEF6 GENE?

ARHGEF6 is a gene located on the X chromosome position 26.3 that codes for an enzyme called Guanine Nucleotide Exchange Factor 6. Diseases or non-disease related traits that are transferred through the X-chromosome are termed “sex-linked”. This enzyme is present in the brain, immune system, and the intestine. In the brain, its highest concentration is in the hippocampus CA1 region, which is important for new memory formation. ARHGEF6 is also responsible for normal neuron growth patterns. ARHGEF6 helps to control neurological spine and neurite growth morphologies. Because of its role in neuronal growth, loss of ARHGEF6 activity results in a decrease in the density of cortical pyramidal neurons. These mismanaged growth morphologies can lead to deficits in autophagy (the breakdown and recycling of cellular components) in microglia and impaired synaptic pruning, which have been linked to behaviors similar to those of ASD.

The ARHGEF6 enzyme also plays a role in immunity. It is present in large amounts in the immune system, especially in T-cells. In the intestine it may play a different role. Studies have shown that ARHGEF6 interacts with strains of bacteria that play a role in inflammatory bowel disease.

ARHGEF6’s role in immunity may help explain the link between environmental exposures and the increasing rates of an autism spectrum disorder spectrum disorder. As we are exposed to more toxic chemicals more every day, males with this mutation may be more susceptible to inflammation caused by toxin exposure. Since 20% of males who tested positive for the gene do not have an autism spectrum disorder spectrum disorder spectrum disorder, knowledge about these “resistant” males undoubtedly will help to find out how to protect the 80% of males that are susceptible to the gene.

HOW DOES THIS GENE RELATE TO THE MUCH HIGHER INCIDENCE OF AN AUTISM SPECTRUM DISORDER IN MALES COMPARED TO FEMALES?

Males receive an X chromosome from their mothers who have 2 X chromosomes while females receive an X chromosome from both their fathers and their mothers. Thus, mothers will transmit the affected gene to their sons while both fathers and mothers transmit the affected gene to their daughters. 

HOW COMMON ARE MUTATIONS IN THIS SPECIFIC GENE?

This mutation is present in about 15% of the population and is present more than twice as often in females than in males because females have two X chromosomes compared to one in males. Our studies so far find no link to the ARHGEF6 mutation and an autism spectrum disorder in females. However our number of female patients was limited. Therefore, no conclusions from this study can be made about how this gene affects human health in females. As we accumulate more data on females we will include it on our website.

WHAT TYPES ARE ILLNESSES ARE ASSOCIATED WITH MUTATIONS TO THIS GENE?

Studies have linked many different health issues with ARHGEF6 mutations. In the intestine, mutations in ARHGEF6 have been associated with several types of diseases. ARHGEF6 has been associated with inflammatory bowel disease, ulcerative colitis, and Crohn’s disease. Mutations in ARHGEF6 can cause major structural changes to the brain and have been linked to an autism spectrum disorder spectrum disorder, mental deficiencies, and schizophrenia.

Blog5.png

WHO SHOULD HAVE THIS GENE TESTED? 

  • Women who are thinking about getting pregnant or who are pregnant

  • Males or females with a history of an autism spectrum disorder in their family

  • Anyone concerned about having a child with an autism spectrum disorder 

WHAT CAN I DO IF I OR MY CHILD TESTS POSITIVE FOR THE ARHGEF6 GENE SNP?

If you or child is positive for the ARHGEF6 gene SNP, it is not a definitive diagnosis of an autism spectrum disorder. It simply means there is a greater risk of developing an autism spectrum disorder. There are many things that can be done to potentially counteract various symptoms and common health problems associated with an autism spectrum disorder. The Great Plains Laboratory, Inc. has specialized in these kinds of specialty diagnostics for more than 20 years, and we recommend treatment strategies that are evidence-based and have a high level of efficacy for many patients. We recommend you partner with a healthcare practitioner who thoroughly understands this biomedical approach to an autism spectrum disorder.  You may contact our laboratory to request a list of these kinds of practitioners in your area.

Genetic susceptibility to an autism spectrum disorder may determine who develops this complex disorder, but factors like nutrient deficiencies, food allergies, toxin exposure, and pathogenic intestinal microbial overgrowth strongly influence the severity of symptoms. Yeast (most commonly, Candida) bacteria (particularly Clostridia), and toxins (both metal and non-metal) all have the potential to act as pathogens. Comprehensive laboratory testing can identify the physiological imbalances that contribute to an autism spectrum disorder and point to an individualized treatment approach. Many of the tests are urine tests and can be run on the same urine sample. Treatments are designed to restore the body to balance and optimize function through nutritional support, diet, detoxification, and reduction of toxic environmental influences. For information and resources, go to www.greatplainslaboratory.com/autism-spectrum-disorders.

Blog4.png

I AM CONCERNED ABOUT DISCRIMINATION AGAINST ME AND/OR MY CHILD BASED ON THE INFORMATION IN THE ARHGEF6 SNP TEST. WHAT ARE CURRENT LEGAL PROTECTIONS IN THE USA?

An excellent description of the laws in the USA regarding genetic discrimination is found on the website of the National Society of Genetic Counselors: http://aboutgeneticcounselors.com/Portals/0/NSGC%20GINA%20Fact%20Sheet%20Feb%202018%20-%20FINAL.pdf?ver=2018-03-09-151406-813&timestamp=1520631152656

At the present time, we do not know what safeguards against discrimination based on genetic testing are available in other countries.

WHAT FORMS ARE REQUIRED TO GET THIS TEST?

Forms that must be completed and submitted are:

  • Test Requisition Form (TRF)

  • Patient/Guardian Informed Consent

HOW DO I COLLECT A SAMPLE? 

  • The sample is collected with a buccal swab which is very similar to a Q-tip®.

  • Rinse your mouth with cold water before you begin collecting your sample and then swallow to remove excess saliva.

  • Collect sample by rubbing the insides of the cheeks of the mouth on all three swabs.

  • Place the swab sleeves containing the dry swabs in the paper envelope included in the kit.

  • Label the envelope with your name and date of sample collection.

  • Ship the test kit back to the laboratory using the shipping mailer provided.

  • More detailed instructions can be found on our website and in the test kits.

Blog6.png

HOW LONG WILL IT TAKE TO GET MY RESULTS?

Results will be available in about 4 weeks.

WILL MY TEST RESULTS BE KEPT CONFIDENTIAL? 

Results are kept confidential according to HIPAA requirements and will only be shared with the patient/guardian and designated healthcare practitioner or genetic counselor who authorized the test.  Results are sent via secure portal or secure e-mail. 

WHO WILL HAVE ACCESS TO MY RESULTS AND HOW WILL THEY BE USED?

Results will only be shared with you as the patient/guardian and healthcare practitioner or genetic counselor who authorized the test. After 60 days, samples will be de-identified in our system and may be used for future research.

WHAT IS THE SIGNIFICANCE OF THIS TEST IF MY SON IS POSITIVE FOR THE ARHGEF6 GENE SNP?

In the study by The Great Plains Laboratory, Inc., 80% of males with the ARHGEF6 gene mutation had an autism spectrum disorder while 20% of males with the ARHGEF6 gene mutation did not develop an autism spectrum disorder. Thus, a baby boy with this gene mutation will have four times the risk of developing an autism spectrum disorder compared to a baby boy who is negative for this gene mutation. Since the development of an autism spectrum disorder decreases markedly with age, boys who are positive for this gene mutation would be expected to have decreased risk of an autism spectrum disorder as they age; new development of an autism spectrum disorder is rare after 5 years of age. However, non-autistic men with the ARHGEF6 gene mutation may have a higher rate of depression, colitis, or other bowel disorder.

Males with this gene who produce children do not transfer this gene to their sons but will transfer the gene to all of their daughters. However, our data so far are insufficient to know whether the presence of one or two of the ARHGEF6 gene mutations in female children increases their risk of developing an autism spectrum disorder.

Blog4.png

WHAT IS THE SIGNIFICANCE OF THIS TEST IF MY SON IS NEGATIVE FOR THE ARHGEF6 GENE SNP?

Males who are negative for this gene SNP will not develop an autism spectrum disorder or other illnesses associated with this gene SNP. However, they could develop an autism spectrum disorder or other illnesses due to other untested genetic factors or environmental factors. About 66% of patients with an autism spectrum disorder did not possess the mutant ARHGEF6 gene.

WHAT IS THE SIGNIFICANCE OF THIS TEST IF A MOTHER OR HER DAUGHTER IS POSITIVE FOR THE ARHGEF6 GENE SNP?

Currently, we have insufficient data to know if females with one or two of the ARHGEF6 gene mutations have an increased risk of developing an autism spectrum disorder or any other illness associated with the ARHGEF6 gene mutations.

Females who have two of the ARHGEF6 gene mutations who bear children have an increased risk of having a boy with an autism spectrum disorder. If a woman with two of the gene mutations (homozygous) is pregnant with a boy child, there is a 100% risk that the boy child will receive the ARHGEF6 gene mutation and an 80% risk that the child will develop an autism spectrum disorder.

Females who have one of the ARHGEF6 gene mutations who bear children have an increased risk of having a boy with an autism spectrum disorder. If pregnant with a boy child, women with one of the ARHGEF6 gene mutations (heterozygous) will have a 50% risk that the boy child will receive the ARHGEF6 gene mutation and a 40% risk that the child will develop an autism spectrum disorder. 

At this time, our data are insufficient to know if women with one or two of the ARHGEF6 gene mutation genes are also at increased risk of having girls with an autism spectrum disorder or other illnesses such as inflammatory bowel disease and depression.

WHO SHOULD I CONTACT IF I HAVE MORE QUESTIONS ABOUT THIS TEST?

Due to the highly technical and sensitive nature of this test, we ask that you connect with one of our genetic testing experts for any additional questions or concerns.  Please send an e-mail to autismrisk@gpl4u.com and one of our experts will respond as soon as possible. 

For a list of references, please visit the Autism Risk Assessment page of our web site here.

If you have any questions about the study or the new Autism Risk Assessment, please contact me at gplblog@gpl4u.com.

New Marker Additions to GPL-SNP1000 DNA Sequencing Profile

BY: MATTHEW PRATT-HYATT, PHD

The number one goal for The Great Plains Laboratory is to provide the best quality results to our clients.  Our GPL-SNP1000 DNA Sequencing Profile has proven to be a great tool in helping provide personalized healthcare to our clients.  The nine pathways we analyze include: methylation, mental health, oxalate metabolism, drug and environmental metabolism/detoxification, gluten sensitivity, cholesterol metabolism, autism risk genes, and transporter gene.  These are crucial biological pathways, which are at the root of many chronic health conditions.  We are now announcing the addition of nine new markers to our already incredibly comprehensive genetic test:

Dopamine Beta Hydroxylase (DBH)
This is an enzyme that catalyzes the oxidation hydroxylation of dopamine to norepinephrine.  DBH can be inhibited by phenolic compounds including those produced by Clostridium species as well as certain organophosphate herbicides and pesticides.  There are two SNPs that can cause decreased activity of DBH.  These are rs2007153 and rs2283123.  These polymorphisms can lead to an increase in dopamine levels and a deficiency in norepinephrine.  Mental health disorders can result because of the imbalance of dopamine and norepinephrine.  Common symptoms can include depression and anxiety.

Paroxonase 1 (PON1)
This is an important enzyme in the metabolism and elimination of many organophosphorus insecticides (PMID: 13032041) and is located mainly in the liver.  PON1 is important in the reduction of atherosclerosis because of its involvement in the protection of high and low density lipoproteins from oxidation.  Individuals with polymorphisms to PON1 are more susceptible to heart disease (PMID: 8675673).  There are two known polymorphisms that can decrease the activity of PON1 and make the individual more susceptible to pesticide exposure, which are Q192R (rs662) and L55M (rs854560).

Hemochromatosis Protein (HFE)
The hemochromatosis gene HFE (high iron) codes for the HFE protein.   This protein is important for regulating the uptake of circulating iron.  This is done by regulating the interaction between transferrin receptor with transferrin.  SNPs to this gene can cause hemochromatosis, a disorder in which the body loads excess iron, which is autosomal recessive.  This means the patient normally needs two bad copies of the gene in order to exhibit symptoms.  There are three SNPs that can lead to hemochromatosis, rs1800562, rs1800730, and rs1799945.  Patients that are homozygous positive for this SNP should have their iron level measured. 

Vitamin K Epoxide Reductase Complex Subunit 1(VKORC1)
This is an enzyme that is necessary for the reduction of vitamin K 2,3-epoxide to its active form, which is important for clotting.  This enzyme is the primary target for the drug warfarin (Coumadin).  The three SNPs that are associated with warfarin sensitivity are rs9923231 (VKORC1*2), rs9934438, and rs8050894.  These polymorphisms can be used in conjuncture with the genotype of Cyp2C9 in order to accurately dose warfarin.

Tryptophan Hydroxylase 2 (TPH2)
This enzyme catalyzes the first and rate-limiting step in the biosynthesis of serotonin. Mutations to this enzyme have been associated with numerous psychiatric diseases including depression, OCD, bipolar disorder, and suicidal behavior.

Major Histocompatibility Complex DQA1 and DQA8
Patients with SNPs to HLA DQA1 and DQA8 have a higher risk of celiac disease.   The HLA-DQA1 and DQA8 are human leukocyte antigen serotype (also called major histocompatibility complex II). The role of this peptide is to present proteins on the surface of cells for identification purposes. This particular serotype presents proteins belonging to a foreign invader on the cells the macrophages, B cells, and dendritic cells in order to activate the helper T cells of the immune system. Proper presentation is critical for immune system activation against pathogens and may possibly be a mediator of autoimmunity.

UDP Glucosyltransferase 1A1 and 1A8 (UGT1A1 and UGT1A8)
These enzymes are important members of the glucuronidation phase II detoxification pathway.  These enzymes catalyze the addition of a glycosyl group from a nucleotide sugar to a small hydrophobic molecule.  The addition of glycosyl groups results in these molecules becoming more water-soluble and easier to excrete. Some of the target molecules for these enzymes include bilirubin, drugs, hormones, and steroids.

The Importance of Genetic Testing for Mental Health

Two weeks ago I talked about how we are starting to move into the age of personalized medicine.  Our goal at The Great Plains Laboratory is to determine what factors lead to chronic illnesses and what treatments may help.  Previously I discussed how the Organic Acids Test (OAT) and the GPL-SNP1000 DNA Sequencing Profile work well together to determine both the risk for and causes of many chronic illnesses and how useful these two tests are in helping practitioners develop individualized treatments.  Last week I specifically discussed the DNA methylation pathway, of the GPL-SNP1000.  This week I am going to go over the mental health pathway of the this same test.  I will talk about what genes are most important, some specific polymorphisms to be aware of, how the OAT can help diagnosis these disorders, and what treatments seem to work best. 

The two most important genes in this pathway are MAO-A (monoamine oxidase A) and COMT (catechol-o-methyltransferase) (Please see Figure 1). Both enzymes are required for metabolizing neurotransmitters critical to mental health. Mutations to either one can have serious consequences relating to how we think, feel, and interpret the world around us.

Figure 1

MAO-A
Monoamine oxidase A is important for the metabolism (breakdown) of biogenic amines such as the neurotransmitters dopamine, norepinephrine, and serotonin (figure 2).  Mutations to this gene have also been linked to depression, borderline personality disorder, and bipolar disorder. 

 

Figure 2

 

There are two different types of polymorphisms involved with MAO-A.  The first type, which is characterized by rs6323 , causes an increase in activity of the enzyme. Rapid metabolism resulting from this mutation causes depletion in the neurotransmitter. This depletion is directly related to the extent of the enzyme activity which can be determined on the Organic Acid test (OAT) by measuring the production of Homovanillic acid (HVA) and Vanillylmandelic acid (VMA) which are the end products of dopamine and epinephrine metabolism (see figure 1).  Patients who are rapid metabolizers will show an increase of HVA of VMA (Figure 3).  Such patients will have a depletion of these neurotransmitters which leads to multiple neurological diseases including depression. Treatment for these polymorphisms includes supporting the methylation pathway which helps to promote the cofactor required for neurotransmitter synthesis and providing neurotransmitter precursors such as tyrosine, B6 and 5-HTP.

Figure 3

A second type of polymorphism to MAO-A is one that decreases activity (rs72554632,  Gln296X), whichcauses a premature stop codon in the gene..  This polymorphismwill lead to a buildup of neurotransmitters, which can lead to the development of Brunner syndrome.  Brunner syndrome is characterized by a decrease of mental capabilities, increased impulsivity, mood swings, and sleep disorders. These individuals will have a decrease of HVA and VMA metabolites on the OAT. Without the benefit of genetic testing, these results could lead a practitioner to treat with neurotransmitter precursors. Increasing neurotransmitters for individuals with this type of mutation would actually exacerbate the condition. Treatments include decreasing the amine containing foods such as fish, cheese, and fruit, taking progesterone to increase MAO; taking inositol(which reduces 5HT2A serotonin receptor), taking riboflavin (increases MAO activity), or taking ginkgo, which has been shown to decrease aggressiveness in MAO-A deficient patients.

COMT
Catechol-O-methltransferase (COMT) is present in the body in two different forms.  The short form is called soluble catechol-O-methyltransferase (S-COMT).  The longer form is called membrane-bound catechol-O-methyltransferase (MB-COMT).   MB-COMT is mainly present in the nerves of the brain, while S-COMT is located in the liver, kidney, and blood.  In the brain, MB-COMT is responsible for degrading neurotransmitters called catecholamines, which include dopamine, epinephrine, and norepinephrine. Therefore the membrane bound form is believed to have a greater affect on mental health, though both forms may be implicated in disease since both are capable of metabolizing catecholamines.

GPL-SNP1000 analyzes six different SNPs for COMT.   Of these, the most extensively studied is a mutation to rs4680 (Val158Met). Despite the many studies available about this mutation, the scientific community is still at odds about the degree to which this mutation causes disease. What is known is that individuals with this mutation have lower activity of the enzyme.  Mutations to COMT will lead to dopamine and epinephrine not being broken down properly, which can be detected by a decrease in the HVA metabolite in the Organic Acids Test.

Figure 4

Interestingly, some individuals may benefit from increased dopamine while others may benefit from less. Dopamine functions differently depending on the area of the brain it is produced in and there are likely other mutation to this gene may also influence its function and expression. These interactions are still being investigated and are why GPL is looking beyond the most common mutation to help inform results.  Conditions associated with these mutations include OCD, depression, and schizophrenia.  Symptomatic patients may benefit from treatment aimed at promoting the enzyme function so that dopamine and epinephrine can be metabolized. This is a SAM dependant enzyme and methylation support can be helpful in patients with this mutation.

APOE
Apolipoprotein E (APOE) combines with lipids in the body to form lipoproteins.  Lipoproteins are responsible for packaging cholesterol and other lipids and carrying them through the bloodstream.  Like so many genes in the human body, this is not its only function. The ApoE protein is involved with more than was originally thought. In this case, it has a role in immune expression, cognitive function, and telomere regulation.  There are four different gene versions of APOE called e1 (the double mutant), e2 (rs7412), e3, and e4 (rs429358).  The most common version is e3, the most detrimental is e4

 Mutations to APOE can lead to an increased risk of developing Alzheimer’s disease. People who inherit even one copy of the APOE e4 allele have an increased risk of developing the disease. Certain mutations to this protein impair the ability of the body to phosphorylate NMDA (glutamate) receptors causing a reduction in activity (Glutamate receptors have been implicated in a number of neuropsychiatric disorders including depression, biopolar disorder, schizophrenia, and Autism (PMID: 12404584, 21315104). While this gene is being extensively studied for its role in Alzheimer’s disease, vulnerable patients may also be predisposed to other psychiatric disorders. (PMID: 25751510, 15557508). Patients with certain ApoE mutations may develop cognitive symptoms well before onset of Alzheimer’s disease (http://psycnet.apa.org/journals/neu/16/2/254/).  Patients with these polymorphisms should look for early signs of the development of Alzheimer’s disease.  Treatment with estrogen has demonstrated some encouraging results.

DAOA
The D-amino acid oxidase activator (DAOA) protein (also known as G72) is a 153 amino acid protein that localizes in the brain, spinal cord, and testis.  This protein is located in the endoplasmic reticulum and the mitochondria cellular compartments.   DAOA is a modulator of D-amino acid oxidase (DAO) activity.  If DAO is hyper activated it can result in a decrease in the D-serine level and hypo function of the NMDA receptor.  Overexpression of DAOA has been found in schizophrenics and those suffering from bipolar disorder.  Mutations to DAOA have been linked to a higher incidence of schizophrenia and bipolar disorder. 

It is important to remember that our genes influence our mental health and well being but do not necessarily determine the eventual outcome. There are countless factors that play an equal role in how we perceive the world including diet and lifestyle.   I believe that understanding the most common mutations and their function is very helpful in diagnosing, treating, and preventing different neurological disorders.  Using the GPL-SNP1000 test in combination with the OAT can further help determine the extent to which our genes are being expressed metabolically. The combination of these two tests can help bring about the best chance to achieve emotional health and physical well being.

Email gplblog@gpl4u.com if you have any questions about this blog post.