Platelet mitochondrial DNA methylation: a potential new marker of cardiovascular disease
Open accessAbstract
BACKGROUND: Platelets are critical in the etiology of cardiovascular disease (CVD), and the mitochondria in these cells serve as an energy source for platelet function. Epigenetic factors, especially DNA methylation, have been employed as markers of CVD. Unlike nuclear DNA methylation, mitochondrial DNA (mtDNA) methylation has not been widely studied, in part, due to debate about its existence and role. In this study, we examined platelet mtDNA methylation in relation to CVD. RESULTS: We measured mtDNA methylation in platelets by bisulfite-PCR pyrosequencing and examined associations of CVD with methylation in mitochondrial genes; cytochrome c oxidase (MT-CO1, MT-CO2, and MT-CO3); tRNA leucine 1 (MT-TL1); ATP synthase (MT-ATP6 and MT-ATP8); and NADH dehydrogenase (MT-MD5). We report that CVD patients have significantly higher mtDNA methylation than healthy controls in MT-CO1 (18.53%, P < 0.0001), MT-CO2 (3.33%, P = 0.0001), MT-CO3 (0.92%, P < 0.0001), and MT-TL1 (1.67%, P = 0.0001), which are involved in ATP synthesis. Platelet mtDNA methylation was not related with age, BMI, and race in this study. CONCLUSIONS: Our results suggest that platelet mtDNA methylation, which could serve as non-invasive and easy-to-obtain markers, may be implicated in the etiology of CVD.
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Altered mtDNA methylation patterns have been linked to human conditions such as cardiovascular disease, colorectal cancer, non-alcoholic steatohepatitis, obesity-related insulin resistance, and Down syndrome.
“Human diseases, including cardiovascular diseases110, colorectal cancer111, non-alcoholic steatohepatitis112, obesity-induced insulin resistance113 and Down syndrome114, have also been associated with changes in mtDNA methylation patterns.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [110]
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- Authors
- Baccarelli, A. A., & Byun, H.-M.
- Affiliations
- Harvard University (US)
- Corresponding author
- Byun, Hyang-Min
- Venue
- Clinical Epigenetics
- Published
- 2015-04-16
- Volume
- 7
- Issue
- 1
- Pages
- 44-44
- ISSN
- 1868-7075 (ISSN-L)
- 1868-7083
- PMC
- PMC4404685
- OpenAlex
- W2147713812
- Cited by
- 168
- References
- 45
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 11 · 2023: 21 · 2022: 26 · 2021: 12 · 2020: 17 · 2019: 13 · 2018: 9 · 2017: 19 · 2016: 12 · 2015: 5
- FWCI
- 6.52
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Clinical Epigenetics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Newcastle University ePrints (Newcastle Univesity) (cc-by)
- Funders
- National Institutes of Health
- National Institute of Environmental Health Sciences (R21ES022694, P30ES000002)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Keywords
- cardiovascular disease, epigenetic biomarkers, cytochrome c oxidase, ATP synthase, NADH dehydrogenase, mitochondrial genes, platelet function, non-invasive biomarkers
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