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GENOMICS: Reaching the tipping point

By Craig Tanio, MD, FACP, IFMCP

Genomics testing has reached the tipping point for those patients who are interested in reaching optimal health or addressing their complex chronic conditions.

Genomics testing is a comprehensive test of your DNA. It describes the very small changes in your DNA that may not cause disease individually, but that collectively can indeed contribute towards disease or health concerns. These changes may take place within a protein in the DNA (e.g., single nucleotide polymorphisms), or can include the deletion of specific genes themselves. Genes are not your destiny, but they can greatly influence how your environment and lifestyle affects your health.

20 years ago, the data was too messy and did not create practical insights. I once helped to write an analysis of the impact of genomics and the sequencing of the human gene on the pharmaceutical industry i. Our findings predicted that the information provided by genomics was overwhelming and that it would take a number of years before insights actually came. This analysis was quite prescient and predicted the decade-long decrease in the productivity of the pharmaceutical industry at the beginning of the 21st century.

20 years later, the situation has changed significantly. The medical literature that supports interventions based on genomics has truly taken off in the past five years. The critical aspect for patients and their providers is to have access to clinical decision support services that are aided by regularly updated monthly medical literature that assists in the making of said decisions. At Rezilir, we actively participate in two major services – IntellXX DNA and Functional Genomics.

How can genomics affect treatment of patients? Genomics reflects the potential of a patient to experience challenges in a particular pathway. For example, in patients who present report autoimmune or potential clinical issues in their detoxification pathways, we have been able to successfully detect the following scenarios which would not have been as easily testable through biomarkers.

· Histamine issues: Mast cell activation syndrome is notoriously difficult to test due to the evanescent nature of markers. Patients with significant variants along their histamine pathways are likely at higher risk. Genomics can be a confirmatory test nevertheless.

· Vitamin B12 issues: Transcobalamin 1 and 2 are vitamin B12 binding proteins that actively help get Vitamin B12 into cells. In particular, transcobalamin 2 is the major method by which B12 routes into the CSF and brain. ii, iii As a result, patients who have a homozygous variant in Transcobalamin 2 and have corresponding neurological symptoms may benefit from a N of 1 trial of Vitamin B12, even if they have a relatively normal serum Vitamin B12. Such a trial can take 2-3 months but can create some profound insights.

· Iron issues: Iron is an often overlooked trigger of chronic inflammation, especially in older adults. One study showed that 13% of adults had signs and biomarkers of iron overloadiv. While iron can be accurately measured through serum biomarkers such as ferritin, iron and iron saturation levels, seeing other genomic contributions to iron and inflammation also known as the Fenton pathway has helped us clinically pay attention to this source of inflammation.

· Reducing the amount of treatment – Genomics offers the potential for more precise approaches to treatment. For example, if we discover genomic variants in 1-2 parts of phase 2 detoxification pathways, we may focus our treatment on those areas and consequently simplify treatment.

At Rezilir, we believe that the number of insights coming from genomic testing will continue to accelerate year after year, and we will continue to discuss these issues in future blog posts.

i Tanio CP, Ma P, Edmunds RC, “Splicing a Cost Squeeze into the Genomics Revolution,” McKinsey Quarterly Spring 2001 ii 1. Akkouh IA, Ueland T, Andreassen OA, et al. Expression of TCN1 in Blood is Negatively Associated with Verbal Declarative Memory Performance. Sci Rep. 2018;8. doi:10.1038/s41598-018-30898-5 iii . Mitchell ES, Conus N, Kaput J. B vitamin polymorphisms and behavior: Evidence of associations with neurodevelopment, depression, schizophrenia, bipolar disorder and cognitive decline. Neuroscience & Biobehavioral Reviews. 2014;47:307-320. doi:10.1016/j.neubiorev.2014.08.006 iv Fleming DJ, Jaques PF et al. Iron status of the free-living, elderly Framingham Heart Study cohort: an iron-replete population with a high prevalence of elevated iron stores Am J Clin Nutr 2001;73:638–46.

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