DNA Methylation As a Biomarker for Monitoring Disease Outcome in Patients with Hypovitaminosis and Neurological Disorders

Overview

Journal Genes (Basel)

Publisher MDPI

Date 2023 Feb 25

PMID 36833292

Authors

Olaia Martinez-Iglesias

Vinogran Naidoo

Lola Corzo

Rocio Pego

Silvia Seoane

Susana Rodriguez

Margarita Alcaraz

Adriana Muniz

Natalia Cacabelos

Ramon Cacabelos

Affiliations

Soon will be listed here.

Abstract

DNA methylation remains an under-recognized diagnostic biomarker for several diseases, including neurodegenerative disorders. In this study, we examined differences in global DNA methylation (5mC) levels in serum samples from patients during the initial- and the follow-up visits. Each patient underwent a blood analysis and neuropsychological assessments. The analysis of 5mC levels revealed two categories of patients; Group A who, during the follow-up, had increased 5mC levels, and Group B who had decreased 5mC levels. Patients with low Fe-, folate-, and vitamin B12- levels during the initial visit showed increased levels of 5mC after treatment when assessed during the follow-up. During the follow-up, 5mC levels in Group A patients increased after treatment for hypovitaminosis with the nutraceutical compounds Animon Complex and MineraXin Plus. 5mC levels were maintained during the follow-up in Group A patients treated for neurological disorders with the bioproducts AtreMorine and NeoBrainine. There was a positive correlation between 5mC levels and MMSE scores, and an inverse correlation between 5mC and ADAS-Cog scores. This expected correlation was observed in Group A patients only. Our study appears to indicate that 5mC has a diagnostic value as a biomarker across different pathologies.

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References

Jin Z, Liu Y . DNA methylation in human diseases. Genes Dis. 2018; 5(1):1-8. PMC: 6147084. DOI: 10.1016/j.gendis.2018.01.002. View

Mastroeni D, McKee A, Grover A, Rogers J, Coleman P . Epigenetic differences in cortical neurons from a pair of monozygotic twins discordant for Alzheimer's disease. PLoS One. 2009; 4(8):e6617. PMC: 2719870. DOI: 10.1371/journal.pone.0006617. View

Bollati V, Galimberti D, Pergoli L, Dalla Valle E, Barretta F, Cortini F . DNA methylation in repetitive elements and Alzheimer disease. Brain Behav Immun. 2011; 25(6):1078-83. PMC: 3742099. DOI: 10.1016/j.bbi.2011.01.017. View

Martinez-Iglesias O, Naidoo V, Cacabelos N, Cacabelos R . Epigenetic Biomarkers as Diagnostic Tools for Neurodegenerative Disorders. Int J Mol Sci. 2022; 23(1). PMC: 8745005. DOI: 10.3390/ijms23010013. View

Nan X, Campoy F, Bird A . MeCP2 is a transcriptional repressor with abundant binding sites in genomic chromatin. Cell. 1997; 88(4):471-81. DOI: 10.1016/s0092-8674(00)81887-5. View

Di Francesco A, Arosio B, Falconi A, Micioni Di Bonaventura M, Karimi M, Mari D . Global changes in DNA methylation in Alzheimer's disease peripheral blood mononuclear cells. Brain Behav Immun. 2014; 45:139-44. DOI: 10.1016/j.bbi.2014.11.002. View

Tuck M, Chan D, Chia D, Godwin A, Grizzle W, Krueger K . Standard operating procedures for serum and plasma collection: early detection research network consensus statement standard operating procedure integration working group. J Proteome Res. 2008; 8(1):113-7. PMC: 2655764. DOI: 10.1021/pr800545q. View

Allen L . Causes of vitamin B12 and folate deficiency. Food Nutr Bull. 2008; 29(2 Suppl):S20-34. DOI: 10.1177/15648265080292S105. View

Mahajan A, Sapehia D, Thakur S, Mohanraj P, Bagga R, Kaur J . Effect of imbalance in folate and vitamin B12 in maternal/parental diet on global methylation and regulatory miRNAs. Sci Rep. 2019; 9(1):17602. PMC: 6879517. DOI: 10.1038/s41598-019-54070-9. View

10.

Kaur G, Rathod S, Ghoneim M, Alshehri S, Ahmad J, Mishra A . DNA Methylation: A Promising Approach in Management of Alzheimer's Disease and Other Neurodegenerative Disorders. Biology (Basel). 2022; 11(1). PMC: 8773419. DOI: 10.3390/biology11010090. View

11.

Romero A, Parada E, Gonzalez-Lafuente L, Farre-Alins V, Ramos E, Cacabelos R . Neuroprotective effects of E-PodoFavalin-15999 (Atremorine®). CNS Neurosci Ther. 2017; 23(5):450-452. PMC: 6492656. DOI: 10.1111/cns.12693. View

12.

Cacabelos R, Carril J, Cacabelos N, Kazantsev A, Vostrov A, Corzo L . Sirtuins in Alzheimer's Disease: SIRT2-Related GenoPhenotypes and Implications for PharmacoEpiGenetics. Int J Mol Sci. 2019; 20(5). PMC: 6429449. DOI: 10.3390/ijms20051249. View

13.

Folstein M, Folstein S, McHugh P . "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975; 12(3):189-98. DOI: 10.1016/0022-3956(75)90026-6. View

14.

Masliah E, Dumaop W, Galasko D, Desplats P . Distinctive patterns of DNA methylation associated with Parkinson disease: identification of concordant epigenetic changes in brain and peripheral blood leukocytes. Epigenetics. 2013; 8(10):1030-8. PMC: 3891683. DOI: 10.4161/epi.25865. View

15.

Robertson K . DNA methylation and human disease. Nat Rev Genet. 2005; 6(8):597-610. DOI: 10.1038/nrg1655. View

16.

Kadmiri N, Said N, Slassi I, El Moutawakil B, Nadifi S . Biomarkers for Alzheimer Disease: Classical and Novel Candidates' Review. Neuroscience. 2017; 370:181-190. DOI: 10.1016/j.neuroscience.2017.07.017. View

17.

Sales A, Joca S . Effects of DNA methylation inhibitors and conventional antidepressants on mice behaviour and brain DNA methylation levels. Acta Neuropsychiatr. 2015; 28(1):11-22. DOI: 10.1017/neu.2015.40. View

18.

Salameh Y, Bejaoui Y, El Hajj N . DNA Methylation Biomarkers in Aging and Age-Related Diseases. Front Genet. 2020; 11:171. PMC: 7076122. DOI: 10.3389/fgene.2020.00171. View

19.

Cano S, Posner H, Moline M, Hurt S, Swartz J, Hsu T . The ADAS-cog in Alzheimer's disease clinical trials: psychometric evaluation of the sum and its parts. J Neurol Neurosurg Psychiatry. 2010; 81(12):1363-8. DOI: 10.1136/jnnp.2009.204008. View

20.

Martinez-Iglesias O, Carrera I, Carril J, Fernandez-Novoa L, Cacabelos N, Cacabelos R . DNA Methylation in Neurodegenerative and Cerebrovascular Disorders. Int J Mol Sci. 2020; 21(6). PMC: 7139499. DOI: 10.3390/ijms21062220. View