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.