Associations between Circulating Biomarkers of One-Carbon Metabolism and Mitochondrial D-Loop Region Methylation Levels
<p>Schematic overview of one-carbon metabolism, adapted from [<a href="#B12-epigenomes-08-00038" class="html-bibr">12</a>]. Main metabolites (in rectangles), enzymes (in circles), and cofactors (in hexagons) are reported. In red are the one-carbon metabolism biomarkers analyzed in the current study. Abbreviations: 5-mTHF, 5-methyltetrahydrofolate; 5-10-methylene THF, 5,10-Methylenetetrahydrofolate; AHCY, S-Adenosylhomocysteine hydrolase; ATP, adenosine triphosphate; B6, vitamin B6; CBS, Cystathionine β-synthase; DNMTs, DNA methyltransferases; DHF, dihydrofolate; dUMP, deoxyuridine monophosphate; dTMP, deoxythymidine monophosphate; GSH, glutathione; MAT, methionine adenosyltransferase; MTHFR, methylenetetrahydrofolate reductase; MTR, methionine synthase; MTRR, methionine synthase reductase; TYMS, thymidilate synthase. Metabolites: 5-mTHF, 5-methyltetrahydrofolate; DHF, dihydrofolate; THF, tetrahydrofolate; dTMP, deoxythymidine monophosphate; dUMP, deoxyuridine monophosphate; SAH, S-adenosylhomocysteine; SAM, S-adenosylmethionine; Vit. B12, vitamin B12.</p> "> Figure 2
<p>Mitochondrial D-loop methylation levels in females and males. The <span class="html-italic">p</span>-value was obtained with the Student-<span class="html-italic">t</span> test.</p> "> Figure 3
<p>Correlation between D-loop methylation levels and age at sampling. The correlation was analyzed using Pearson’s correlation coefficient.</p> "> Figure 4
<p>Folate (<b>A</b>), homocysteine (<b>B</b>), and vitamin B12 (<b>C</b>) in females and males. The <span class="html-italic">p</span>-value was obtained with the Student-<span class="html-italic">t</span> test.</p> "> Figure 5
<p>Correlation between folate (<b>A</b>), homocysteine (<b>B</b>), and vitamin B12 (<b>C</b>) circulating levels and age at sampling. The correlations were analyzed using Pearson’s correlation coefficient.</p> "> Figure 6
<p>Correlations among D-loop methylation and folate (<b>A</b>), homocysteine (<b>B</b>), and vitamin B12 (<b>C</b>) circulating levels. The correlation was analyzed using Pearson’s correlation coefficient.</p> "> Figure 7
<p>D-loop methylation levels in individuals below and within reference values (RV) of folate (<b>A</b>), within and above the RV of homocysteine (<b>B</b>), and in individuals below, within, and above the RV of vitamin B12 (<b>C</b>). <span class="html-italic">p</span>-value obtained with ANCOVA including age as the covariate.</p> "> Figure 8
<p>Comparison of folate (<b>A</b>), homocysteine (<b>B</b>), and vitamin B12 (<b>C</b>) circulating levels between samples with an unmethylated D-loop and those with a methylated D-loop. <span class="html-italic">p</span>-value obtained with ANCOVA including age and sex as covariates.</p> ">
Abstract
:1. Introduction
2. Results
2.1. Description of Sample Population
2.2. Influence of Sex and Age at Sampling on mtDNA Methylation and Circulating Biomarkers of One-Carbon Metabolism
2.3. Associations between Circulating Biomarkers of One-Carbon Metabolism and D-Loop Methylation
3. Discussion
4. Materials and Methods
4.1. Main Information on Enrolled Subjects in the Study
4.2. One-Carbon Metabolism Biomarker Analyses
4.3. Methylation-Sensitive–High-Resolution Melting (MS-HRM) Analyses for the Quantification of mtDNA Methylation
4.4. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Folate | Homocysteine | Vitamin B12 | |
---|---|---|---|
Sample concentration a | 6.5 ± 4.0 ng/mL (2.5–29.5) | 15.4 ± 6.0 µmol/L (4.1–34.2) | 469.5 ± 275.0 pg/mL (398–1200) |
Reference concentration b | 4.6–18.7 ng/mL | 4.3–11.1 µmol/L | 191–663 pg/mL |
Samples below the reference range c | 25 (26.6%) | 1 (1.1%) | 10 (10.6%) |
Samples within the reference range c | 67 (71.3%) | 30 (31.9%) | 69 (73.4%) |
Samples above the reference range c | 2 (2.1%) | 63 (67.0) | 15 (16%) |
Sequence (5′→3′) | Annealing Temperature | Amplicon Size | Nucleotide Position | Number of CpG Sites | |
---|---|---|---|---|---|
Primer forward | GGAGTTTTTTATGTATTTGGTATTTT | 56 °C | 222 bp | 35–256 (GenBank: J01415.2) | 10 |
Primer reverse | ACAAACATTCAATTATTATTATTATATCCT |
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Stoccoro, A.; Lari, M.; Migliore, L.; Coppedè, F. Associations between Circulating Biomarkers of One-Carbon Metabolism and Mitochondrial D-Loop Region Methylation Levels. Epigenomes 2024, 8, 38. https://doi.org/10.3390/epigenomes8040038
Stoccoro A, Lari M, Migliore L, Coppedè F. Associations between Circulating Biomarkers of One-Carbon Metabolism and Mitochondrial D-Loop Region Methylation Levels. Epigenomes. 2024; 8(4):38. https://doi.org/10.3390/epigenomes8040038
Chicago/Turabian StyleStoccoro, Andrea, Martina Lari, Lucia Migliore, and Fabio Coppedè. 2024. "Associations between Circulating Biomarkers of One-Carbon Metabolism and Mitochondrial D-Loop Region Methylation Levels" Epigenomes 8, no. 4: 38. https://doi.org/10.3390/epigenomes8040038
APA StyleStoccoro, A., Lari, M., Migliore, L., & Coppedè, F. (2024). Associations between Circulating Biomarkers of One-Carbon Metabolism and Mitochondrial D-Loop Region Methylation Levels. Epigenomes, 8(4), 38. https://doi.org/10.3390/epigenomes8040038