Platelet mitochondrial DNA methylation predicts future cardiovascular outcome in adults with overweight and obesity

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dc.authoridCorsi, Sarah/0000-0002-8680-7870
dc.authoridCAYIR, AKIN/0000-0002-2014-6635
dc.authoridVigna, Luisella/0000-0001-5014-721X
dc.authoridByun, Hyang-Min/0000-0002-6278-3165
dc.contributor.authorCorsi, Sarah
dc.contributor.authorIodice, Simona
dc.contributor.authorVigna, Luisella
dc.contributor.authorCayir, Akin
dc.contributor.authorMathers, John C.
dc.contributor.authorBollati, Valentina
dc.contributor.authorByun, Hyang-Min
dc.date.accessioned2025-01-27T21:04:03Z
dc.date.available2025-01-27T21:04:03Z
dc.date.issued2020
dc.departmentÇanakkale Onsekiz Mart Üniversitesi
dc.description.abstractBackground The association between obesity and cardiovascular disease (CVD) is proven, but why some adults with obesity develop CVD while others remain disease-free is poorly understood. Here, we investigated whether mitochondrial DNA (mtDNA) methylation in platelets is altered prior to CVD development in a population of adults with overweight and obesity. Methods We devised a nested case-control study of 200 adults with overweight or obesity who were CVD-free at baseline, of whom 84 developed CVD within 5 years, while 116 remained CVD-free. Platelet mtDNA was isolated from plasma samples at baseline, and mtDNA methylation was quantified in mitochondrially encoded cytochrome-C-oxidase I (MT-CO1; nt6797 and nt6807), II (MT-CO2; nt8113 and nt8117), and III (MT-CO3; nt9444 and nt9449); tRNA leucine 1 (MT-TL1; nt3247 and nt3254); D-loop (nt16383); tRNA phenylalanine (MT-TF; nt624); and light-strand-origin-of-replication (MT-OLR; nt5737, nt5740, and nt5743) by bisulfite-pyrosequencing. Logistic regression was used to estimate the contribution of mtDNA methylation to future CVD risk. ROC curve analysis was used to identify the optimal mtDNA methylation threshold for future CVD risk prediction. A model was generated incorporating methylation at three loci (score 0, 1, or 2 according to 0, 1, or 2-3 hypermethylated loci, respectively), adjusted for potential confounders, such as diastolic and systolic blood pressure, fasting blood glucose, and cholesterol ratio. mtDNA methylation at MT-CO1 nt6807 (OR = 1.08, 95% CI 1.02-1.16; P = 0.014), MT-CO3 nt9444 (OR = 1.22, 95% CI 1.02-1.46, P = 0.042), and MT-TL1 nt3254 (OR = 1.30, 95% CI 1.05-1.61, P = 0.008) was higher at baseline in those who developed CVD by follow-up, compared with those who remained CVD-free. Combined use of the three loci significantly enhanced risk prediction, with hazard ratios of 1.38 (95% CI 0.68-2.78) and 2.68 (95% CI 1.41-5.08) for individuals with score 1 or 2, respectively (P = 0.003). Methylation at these sites was independent of conventional CVD risk factors, including inflammation markers, fasting blood glucose concentration, and blood pressure. Conclusions Methylations of MT-CO1, MT-CO3, and MT-TL1 are, together, strong predictors of future CVD incidence. Since methylation of these mtDNA domains was independent of conventional CVD risk factors, these markers may represent a novel intrinsic predictor of CVD risk in adults with overweight and obesity.
dc.description.sponsorshipNIH (NIEHS) [R21ES022694]; European Research Council [ERC-2011-StG 282413]
dc.description.sponsorshipThis work has been supported by the NIH (NIEHS, R21ES022694 to HMB) and by the European Research Council (ERC-2011-StG 282413 to VB).
dc.identifier.doi10.1186/s13148-020-00825-5
dc.identifier.issn1868-7075
dc.identifier.issn1868-7083
dc.identifier.issue1
dc.identifier.pmid32066501
dc.identifier.scopus2-s2.0-85079624045
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1186/s13148-020-00825-5
dc.identifier.urihttps://hdl.handle.net/20.500.12428/27535
dc.identifier.volume12
dc.identifier.wosWOS:000517120400001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherBMC
dc.relation.ispartofClinical Epigenetics
dc.relation.publicationcategoryinfo:eu-repo/semantics/openAccess
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WoS_20250125
dc.subjectmtDNA
dc.subjectDNA methylation
dc.subjectPlatelets
dc.subjectCVD
dc.subjectObesity
dc.titlePlatelet mitochondrial DNA methylation predicts future cardiovascular outcome in adults with overweight and obesity
dc.typeArticle

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