Methylation Panel

A Personalised Approach to Healthy Aging

The Methylation Panel is an innovative test designed to offer insight into the critical biochemical methylation pathway. Methylation metabolites are measured using plasma and whole blood, and genetic single nucleotide polymorphisms (SNPs) are analysed via buccal swab. The results are synthesised on a front-page Interpretation-at-a-Glance (IAAG) graphic for quick methylation status assessment. Within the report, results are shown in a methylation pathway graphic to provide a clear understanding of the biochemistry involved.

What is Methylation?

Methylation is a chemical process that happens billions of times per second in every cell of the body.¹ Methyl groups are transferred and donated between many different molecules which change their structure and function. Methyl groups act like billions of switches which turn genes on or off, help regulate mood, detoxify hormones, produce energy, and promote healthy aging.

Vitamins, minerals, and amino acids from the diet are needed to keep this process running smoothly. There are also genetic factors and oxidative stressors which can affect how well this pathway works.²

Why is Methylation important?

Methylation is needed to create DNA and RNA and regulate gene expression. It helps make creatine, which is needed for skeletal muscle contraction. Methylation is involved in basic energy production, fat metabolism, immune responses, vascular health, and cell membrane repair. It produces and metabolises neurotransmitters to regulate mood. Methylation also works to neutralise toxins and hormones.

Methylation defects have been associated with many clinical conditions including, but not limited to cancer, autism, ADHD, congenital and neural tube defects, cognitive decline, depression, cardiovascular disease, and schizophrenia.^3-11

Which patients can benefit from the Methylation Panel?

Because of its all-encompassing role in basic human physiology, the range of symptoms associated with methylation defects is broad. The Methylation Panel can offer insight in patients with:

• questionable detoxification (patients who take hormone therapy, drink alcohol, or have toxin exposure)^12-14
• cancer risk^7,15-17
• cardiovascular disease (non-coronary atherosclerosis, hypertension, coronary artery disease)^10,18-20
• psychiatric and mood disorders (schizophrenia, bipolar disorder, anxiety, depression)^5,7,21,22
• neurologic disorders (Parkinson's disease, cognitive decline)^9,23-25
• chronic fatigue²⁶

Genova's Methodology

Analytes are measured utilising Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS) except for glutathione which is a colorimetric assay developed for an automated chemistry platform. The genetic SNPs are assessed via pyrosequencing.

What advantage does the Methylation Panel offer compared to other diagnostics?

Genova's Methylation Panel combines biomarkers with genetic information in one profile. Some genetic predispositions are not always expressed, therefore seeing combined results offers greater insight.

Not only does the Methylation Panel assess the methylation cycle, but it also incorporates the folate cycle and transsulfuration. Because these three processes are interconnected, the Methylation Panel is able to provide a complete picture regarding methylation status.

How are the results of the Methylation Panel helpful?

The Methylation Panel can uncover needs for nutritional support such as amino acids, vitamins, and minerals. Knowing this can help guide dietary and nutraceutical treatment plans. Additionally, knowing genetic predispositions can help focus supplementation to override potential methylation defects.

References

1. Baric I, Staufner C, Augoustides-Savvopoulou P, et al. Consensus recommendations for the diagnosis, treatment and follow-up of inherited methylation disorders. J Inherit Metab Dis. 2017;40(1):5-20.
2. Locasale JW. Serine, glycine and one-carbon units: cancer metabolism in full circle. Nature Rev Cancer. 2013;13(8):572.
3. Duthie SJ. Folic acid deficiency and cancer: mechanisms of DNA instability. Br Med Bull. 1999;55(3):578-592.
4. Refsum H, Ueland PM, Nygard O, Vollset SE. Homocysteine and cardiovascular disease. Ann Rev Med. 1998;49:31-62.
5. Miller AL. The methylation, neurotransmitter, and antioxidant connections between folate and depression. Alt Med Rev. 2008;13(3):216-227.
6. Troesch B, Weber P, Mohajeri MH. Potential Links between Impaired One-Carbon Metabolism Due to Polymorphisms, Inadequate B-Vitamin Status, and the Development of Alzheimer's Disease. Nutrients. 2016;8(12).
7. Schalinske KL, Smazal AL. Homocysteine imbalance: a pathological metabolic marker. Adv Nutr. 2012;3(6):755-762.
8. Grayson DR, Guidotti A. The dynamics of DNA methylation in schizophrenia and related psychiatric disorders. Neuropsychopharmacology. 2013;38(1):138.
9. Dayon L, Guiraud SP, Corthésy J, et al. One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond. Alzheimers Res Ther. 2017;9(1):43.
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11. Nardone S, Sharan Sams D, Reuveni E, et al. DNA methylation analysis of the autistic brain reveals multiple dysregulated biological pathways. Transl Psychiatry. 2014;4(9):e433.
12. Zakhari S. Alcohol Metabolism and Epigenetics Changes. Alcohol Res. 2013;35(1):6-16.
13. Kharbanda KK. Alcoholic liver disease and methionine metabolism. Semin Liver Dis. 2009;29(2):155-165.
14. Bardag-Gorce F, Oliva J, Wong W, et al. S-adenosylmethionine decreases the peak blood alcohol levels 3 h after an acute bolus of ethanol by inducing alcohol metabolizing enzymes in the liver. Exp Mol Pathol. 2010;89(3):217-221.
15. Zhao Y, Li JS, Guo MZ, Feng BS, Zhang JP. Inhibitory effect of S-adenosylmethionine on the growth of human gastric cancer cells in vivo and in vitro. Chin J Cancer. 2010;29(8):752-760.
16. Pouliot MC, Labrie Y, Diorio C, Durocher F. The Role of Methylation in Breast Cancer Susceptibility and Treatment. Anticancer Res. 2015;35(9):4569-4574.
17. Pascale RM, Feo CF, Calvisi DF, Feo F. Deregulation of methionine metabolism as determinant of progression and prognosis of hepatocellular carcinoma. Transl Gastroenterol Hepatol. 2018;3:36.
18. Wang X, Falkner B, Zhu H, et al. A genome-wide methylation study on essential hypertension in young African American males. PLoS One. 2013;8(1):e53938.
19. Obeid R, Herrmann W. Homocysteine and lipids: S-adenosyl methionine as a key intermediate. FEBS letters. 2009;583(8):1215-1225.
20. Lai CQ, Parnell LD, Troen AM, et al. MAT1A variants are associated with hypertension, stroke, and markers of DNA damage and are modulated by plasma vitamin B-6 and folate. Am J Clin Nutr. 2010;91(5):1377-1386.
21. Papakostas GI, Cassiello CF, Iovieno N. Folates and S-adenosylmethionine for major depressive disorder. Can J Psychiatry. 2012;57(7):406-413.
22. Sugden C. One-carbon metabolism in psychiatric illness. Nutr Res Rev. 2006;19(1):117-136.
23. Obeid R, Schadt A, Dillmann U, Kostopoulos P, Fassbender K, Herrmann W. Methylation status and neurodegenerative markers in Parkinson disease. Clin Chem. 2009;55(10):1852-1860.
24. Dayon L, Guiraud SP, Corthésy J, et al. ONE-CARBON METABOLISM, COGNITIVE IMPAIRMENT AND CSF MARKERS OF ALZHEIMER PATHOLOGY: HOMOCYSTEINE AND BEYOND. Alzheimers Dement. 2017;13(7):P705.
25. Smith AD, Refsum H. Homocysteine, B vitamins, and cognitive impairment. Annu Rev Nutr. 2016;36:211-239.
26. de Vega WC, Vernon SD, McGowan PO. DNA methylation modifications associated with chronic fatigue syndrome. PLoS One. 2014;9(8):e104757.