Current Research

Autism Research

The NutriGenetic Research Institute is starting a Research Project to determine if genomic functional pathways are impaired in Autism Spectrum Disorder (ASD) and PANS/PANDAS. You and your clients are invited to participate in a research study involving ASD and PANS/PANDAS. If you decide to participate, you or you clients will only be asked to provide your 23andMe Raw Data. At this time we are only accepting 23andMe Version 4 raw data file. At no time will your or your clients name or health information be given out. The purpose of the study is to compare the genetics of a large group of individuals dealing with ASD and PANS/PANDAS as it relates to sulfation, antioxidant production and the factors involved in the “NADPH Steal”.

If you have any questions about the ASD and PANS/PANDAS study, please feel free to contact our research team.

Callie Zerby – Research Assistant 
research@nutrigeneticresearch.org | 717-466-5700 ext. 312

Laura Rowe – Client Care Coordinator
laurar@tolhealth.com | 717-733-2003 ext. 307


Past Research

Chronic Lyme & DNA Study

NutriGenetic Research Institute is pleased to share its multi-phase research study on Genetics and Chronic Lyme Disease.

PHASE I – June 2016
“Higher Levels of Genetic Variants (SNPs) Found in those with Chronic Lyme Disease”
Presented by Bob Miller, CTN to the International Lyme & Associated Diseases Society (ILADS) at the 6th European Conference in Helsinki, Finland

Abstract: 192 participants, from around the world, voluntarily submitted their genome for a global contrast to data supplied by the 1000 Genome Phase 3 Project.  Participants’ genomes were evaluated through a 23andMe-supplied analysis. We examined 350 genes that are involved with mitochondrial function, methylation, neurotransmitter production, antioxidant production, and patterns that may result in excess production of oxidative stress, including superoxide, glutamate, ammonia and peroxynitrite. The data collected suggests unique genetic variations may be found in individuals with Chronic Lyme Disease. Compensating for the variants to reduce iron oxidation and improve methylation may be a helpful therapy for those with Chronic Lyme.

Read the final findings of the Chronic Lyme & DNA Study.

View the Helsinki ILADS Study #1 Poster Presentation.

Watch a video that highlights the final findings of the Chronic Lyme & DNA Study.

IMG_0548-Bob-Miller-NGRI-poster-300x225.jpg

PHASE II – November 2016
“Higher Levels of Genetic Variants (SNPs) Found in those with Chronic Lyme Disease”
Presented by Bob Miller, CTN to ILADS at the 17th Annual Scientific Session in Philadelphia, PA

Abstract: To determine if those with Chronic Lyme Disease may have a unique genetic pattern that may create excess inflammation or suppress the immune system, the NutriGenetic Research Institute compared 1,298 genes of a group of 360 individuals who identified as having chronic Lyme to the data supplied by the 1000 Genome Phase 3 Project. The reference and alternate alleles for each of the SNPs (Single Nucleotide Polymorphisms) were determined using the HaploReg v4.1 database. Formulas determined the top 65 genes with more variants in those with chronic Lyme than the control group. Neurotransmitter genes represented 40 of the top 65 genes with the most variants. This analysis will focus on glutamate, dopamine and cannabinoid SNPs.

View the Philadelphia ILADS Conference Study #2 Poster Presentation


Phase III – May 2017
“Higher Levels of Genetic Variants (SNPs) Found in those with Chronic Lyme Disease”
Presented by Bob Miller, CTN to ILADS at the 7th European Conference in Paris, France

Abstract: Genetic mutations (SNPs) can lead to increased free radicals, increased toxic substances, and reduced antioxidant protection causing difficulty detoxing and a weakened immune system that may allow Lyme to be resistant to traditional treatment. To evaluate this hypothesis, 391 participants reporting chronic Lyme disease from around the world voluntarily submitted their 23andMe supplied analysis genome for a global contrast to data supplied by the 1000 Genome Project. We evaluated genes that when variated would increase iron levels, and decrease the antioxidant capacity of the body. The reference and alternate alleles for each of the SNPs were determined using the HaploReg v4.1 database. This data was then compared to data supplied by the 1000 Genome Phase 3 Project. The ratio of SNPs between the Chronic Lyme Group and the Genome Project study was then calculated.

View the Paris ILADS Study #3 Poster Presentation.

3.jpg

4.jpg

Phase IV – November 2017
"Increased Genetic Variants Associated with Reduced Autophagy and Increased mTOR in Chronic Lyme Disease Patients"
Presented by Bob Miller, CTN and Matthew Miller to ILADS at the 18th Annual Scientific Session in Boston, MA

Abstract: Some patients with Lyme disease do not respond well to treatment due to difficulty with inflammation and detoxification. Autophagy supports detoxification by recycling old cells and clearing viruses, bacteria, mold, and toxic substances [1].  The mammalian target of rapamycin (mTOR) coordinates cell growth with the growth factor and nutrient and energy status of the cell. Consequently, it increases energy production, but creates products that need to be cleared. Autophagy contributes to clearing the cells of all irreversibly oxidized biomolecules (proteins, DNA, and lipids). However, autophagy is most active when mTOR is decreased [2]. Hormones (xenoestrogens, dairy, and meats), growth factors (dairy, and meats), iron (iron enriched foods), glutamate (MSG & pesticides), insulin (high sugar foods), EMF, leucine, arginine, and folate all stimulate mTOR, which are all now more prevalent in the food supply and environment. Consequently, environmental factors, endogenous conditions, and genetic variants can contribute to higher mTOR activity and reduced autophagy. It has been projected that increased mTOR and autophagy related genetic variation may be found within individuals diagnosed with Chronic Lyme disease. To evaluate this hypothesis, 391 participants with Lyme disease submitted their 23andMe supplied genome for a contrast to the 1000 Genome Project [3]. We evaluated genes that when variated would stimulate mTOR and inhibit autophagy. The reference and alternate alleles for each of the SNPs were determined using the HaploReg v4.1 database [4]. The ratio of SNPs between the Chronic Lyme Group and the Genome Project was calculated. The genetic analysis found increased variants in the genes that would stimulate mTOR from epigenetic factors and the genes that would support autophagy.

View the Boston ILADS Study #4 Poster Presentation.


Phase V – June 2018
"Increased Genetic Variants Found in Acetylation & Lipid Synthesis Genes in Chronic Lyme Disease Patients"
Presented by Bob Miller, CTN to ILADS at the 8th European Conference in Warsaw, Poland

Abstract: Some patients with Lyme disease do not respond well to treatment: it has been hypothesized this may be due to difficulty with detoxification and inflammation. Xenobiotics such as plastics, industrial chemicals, drugs, pesticides, fragrances, and environmental pollutants need to be detoxified by the body [1]. Phase I CYP450 enzymes and Phase II conjugation pathways are needed to eliminate these toxins through the urine, bile, and stool [2]. The balance between protein acetylation and deacetylation plays a critical role in the regulation of gene expression, signaling pathways, and affects a large range of cellular processes, many related to detoxification. Acetylation is the Phase II Conjugation Reaction process of introducing an acetyl functional group (acetyl-CoA) onto a chemical compound by N-Acetyltransferase (NAT). Acetylation can alter gene expression epigenetically. Acetylation is an important route of metabolism for xenobiotics [3]. Deacetylation is the removal of an acetyl group. For proper acetylation, there needs to be an adequate supply of acetyl-CoA. The PANK genes are responsible for catalyzing the ATP-dependent phosphorylation of pantothenate (vitamin B5) to create 4′-phosphopantothenate, which is needed to create adequate Acetyl-CoA [4]. The NAT enzymes are responsible for carrying out acetylation of the xenobiotics [5]. Acetyl-CoA is also needed for the expression of Nrf2 and ARE (Antioxidant Response Element), which make glutathione for the conjugation of xenobiotics [6]. The ACAT2 gene is an enzyme involved in lipid metabolism, which results in the creation of hormones, DHEA, and cortisol [7].

View the Warsaw ILADS Study #5 Poster Presentation.

5.jpg

6.jpg

Phase VI – November 2018
"Increased Genetic Variants in Heme Pathway and Mast Cell Genes in Chronic Lyme Disease Patients"
Presented by Bob Miller, CTN to ILADS at the 2018 Annual Conference in Chicago, IL

Abstract: Some patients with Lyme disease do not respond well to treatment, it has been hypothesized this may be due to difficulty with detoxification. Heme proteins play a significant role not only in hemoglobin production, but also play a significant role in antioxidant protection by contributing to the production of bilirubin, supporting SUOX (sulfite to sulfate.), NOS (Nitric Oxide Synthase), NADPH (supports antioxidant recycling), and GSH (Glutathione). For proper heme production, there are seven steps, each regulated by an enzyme and various cofactors. The ALAD, CPOX and FECH enzymes are critical to heme synthesis while HMOX catalyzes heme degradation, responsible for multiple critical processes related to controlling inflammation. Mast cells play an important role in the body, but can be detrimental when overactive. The KIT, RAD50, HRH1, FCER1A and DARC genes are related to mast cell activity and responses to mast cell activation. The purpose of this research was to evaluate whether treatment-resistant Lyme disease patients have increased levels of variants in genes involved in heme production, utilization, and mast cell activation. 421 participants with Lyme disease submitted their 23andMe supplied genome for a contrast to the 1000 Genome Project. The major and minor alleles for each of the SNPs were determined using the 1000 Genome Project. The ratio of SNPs between the Chronic Lyme Group and the Genome Project was calculated.

View the Chicago ILADS Phase #6 Poster


Phase VII – June 20019
"Increased Genetic Variants in the Genes related to the Production and Utilization of NAD+ and NADPH in Lyme Patients"
Presented by Bob Miller, CTN to ILADS at the 2019 8th European Conference in Madrid, Spain.

Abstract: Environmental toxicity has increasingly become the focus of research as more evidence points to the cumulative effects of environmental toxins on the immune system and creating a toxic overload that makes it more challenging to remove pathogens. Molecules that play an integral role in removal of environmental toxins are NAD+ and NADPH
NAD+ plays a critical role in supporting:

- The PARP enzymes that support DNA repair [1].

- The SIRT3 enzyme that supports the longevity related FOXO3 gene, helps create the critical anti-oxidants Superoxide Dismutase (SOD) and Catalase, and also supports Autophagy, an integral process to clear dead cells, toxins and pathogens. SIRT3 also supports the Urea Cycle, the production of NADPH and energy creation in the mitochondria [2,3,4].

- The SIRT1 enzyme that supports Vitamin D receptors, superoxide dismutase and slows mTOR. This is important because mTOR inhibits autophagy and in excess will promote inflammation [5,6,7].

-  The creation of NADPH, the molecule responsible for converting oxidized glutathione and threodixin back to reduced, a cofactor for Nitric Oxide production and is needed for energy production in the Krebs cycle [8,9,10]. Lack of NADPH will impede a critical Phase II detoxification pathway, Glutathione Conjugation, and allow the oxidized glutathione to create the free radicals superoxide and peroxynitrite [11,12].

To determine if unique genetic patterns in NAD+ and NADPH exist with chronic Lyme patients, we analyzed functional and detoxification pathways genetic patterns from 421 participants, who submitted their 23andMe genome for a global contrast to data supplied by the 1000 Genome Phase 3 Project. The reference and alternate alleles for each of the SNPs were determined using the HaploReg v4.1 database The ratio of SNPs in pathways related to antioxidant production, excess free radical production, phase I and Phase II pathways, and Autophagy was compared between the chronic Lyme group and the 1000 Genome data.

IMG_1725.jpg

If you are interested in learning more about your own unique DNA and participating in future NutriGenetic Research Institute studies, we utilize data from the Your Genomic Resource DNA test.