Platelet mitochondrial DNA methylation: a potential new marker of cardiovascular disease

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.