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. 2023 Jan 30;14(2):365.
doi: 10.3390/genes14020365.

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

Olaia Martínez-Iglesias  1 , Vinogran Naidoo  1 , Lola Corzo  1 , Rocío Pego  1 , Silvia Seoane  1 , Susana Rodríguez  1 , Margarita Alcaraz  1 , Adriana Muñiz  1 , Natalia Cacabelos  1 , Ramón Cacabelos  1
Affiliations

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

Olaia Martínez-Iglesias et al. Genes (Basel). .

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.

Keywords: DNA methylation; biomarker; folic acid; psychometric testing; vitamin B12.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Analysis of global DNA methylation (5mC, %) in blood samples from patients with the diagnoses of neurological disorders and/or hypovitaminosis. (A) 5mC levels were measured in these patients (n = 98) during the first visit and then during the clinical follow-up. (B) Patients (n = 51; Group A) whose 5mC levels were found to be higher during the follow-up visit than during the initial consult. (C) Patients (n = 47; Group B) whose 5mC levels decreased during the follow-up visit versus the initial visit. Data are presented as the mean ± S.E.M; paired t test (** p < 0.01, *** p < 0.001). 5mC, 5-methylcytosine.
Figure 2
Figure 2
The relationship between Fe levels and global DNA methylation in patient serum samples. (A) Correlation analysis to test the association between Fe and 5mC levels in serum samples from patients in Group A (n = 51) and (B) from patients in Group B (n = 47). Fe levels measured during the initial- and follow-up visits were compared between patients in (C) Group A and (D) Group B. Data are presented as the mean ± S.E.M; paired t test. 5mC, 5-methylcytosine; Fe, iron.
Figure 3
Figure 3
The relationship between folate levels and global DNA methylation in patient serum samples. (A) Correlation analysis to test the association between folic acid and 5mC levels in serum samples from patients in Group A (n = 51) and (B) from patients in Group B (n = 47). Data points indicate individual patient values. Folate levels measured during the initial- and follow-up consults were compared between patients in (C) Group A and (D) Group B. Data are presented as the mean ± S.E.M; paired t tests (*** p < 0.001). 5mC, 5-methylcytosine.
Figure 4
Figure 4
The relationship between vitamin B12 level and global DNA methylation in patient serum samples. (A) Correlation analysis to test the association between vitamin B12 and 5mC levels in serum samples from patients in Group A (n = 51) and (B) from patients in Group B (n = 47). Vitamin B12 levels measured during the initial- and follow-up consults were compared between patients in (C) Group A and (D) Group B. Data are presented as the mean ± S.E.M; paired t test (* p < 0.05). 5mC, 5-methylcytosine.
Figure 5
Figure 5
Correlation analyses of the relationship between patient MMSE scores and levels of global DNA methylation during clinical follow-up. (A) The association between MMSE scores and 5mC levels in (A) all patients (n = 86), (B) patients in Group A (n = 51), and (C) patients in Group B (n = 35). Data points indicate individual patient values. Pearson correlation was used to establish statistical correlation. 5mC, 5-methylcytosine; MMSE, Basal Mini-Mental State Examination.
Figure 6
Figure 6
Correlation analyses of the relationship between patient ADAS-Cog score and levels of global DNA methylation during clinical follow-up. (A) The association between the total ADAS-Cog scores and 5mC levels in all patients (n = 35). (B) Correlation analysis to test the association between total ADAS-Cog scores and 5mC levels in patients from Group A (n =24), and (C) patients from Group B (n =11). Data points indicate individual patient values. Pearson correlation was used to establish statistical correlation. 5mC, 5-methylcytosine; ADAS, Alzheimer’s Disease Assessment Scale; ADAS-Cog, ADAS-cognitive.
Figure 7
Figure 7
Pie charts depicting the relationship between GDS stages and levels of global DNA methylation (5mC) in (A) patients (n = 29; Group A) whose 5mC levels were found to be higher during the follow-up consultation than during the initial visit, and (B) patients (n = 21; Group B) whose 5mC levels did not increase during the follow-up versus the initial visit. GDS stages 1 and 2 indicate normal cognitive function, and higher GDS stages indicate progressive cognitive impairment. 5mC, 5-methylcytosine; GDS, Global Deterioration Scale.
Figure 8
Figure 8
The relationship between vitamins, iron supplements, and nutraceutical bioproducts and global DNA methylation in patient serum samples. 5mC levels were compared in patients whose 5mC levels were higher during the follow-up than during the initial visit and who were, or were not, treated with (A) folate, (B) Hidroxil-B1-B6-B12, (C) Tardyferon, (D) Animon Complex®, and (E) MineraXin PlusTM. Data are presented as the mean ± S.E.M; one way ANOVA and Bonferroni post hoc test (* p < 0.05; ** p < 0.01). 5mC, 5-methylcytosine.
Figure 9
Figure 9
The relationship between pharmacotherapies for brain disorders and global DNA methylation in patient serum samples. Global DNA methylation levels were compared in patients whose 5mC levels were higher during the follow-up than during the initial visit and who were, or were not, treated with (A) Actron, (B) Tryptizol, (C) Deprax, (D) Diazepam, (E) Varson, (F) Somazine, (G) AtreMorineTM, and (H) NeoBrainine®. Data are presented as the mean ± S.E.M; one way ANOVA and Bonferroni post hoc test (* p < 0.05; ** p < 0.01; *** p < 0.001). 5mC, 5-methylcytosine.
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