title: Mitochondrial mutations are associated with atherosclerotic lesions in the human aorta.
abstract: Somatic mutations of the human mitochondrial genome can be a possible determinant of atherosclerosis. To test this possibility, forty mitochondrial mutations were analyzed in the present study in order to see which of these mutations might be associated with atherosclerosis. Ten mitochondrial mutations belonging to mitochondrial genes MT-RNR1 (rRNA 12S); MT-TL1 (tRNA-Leu, recognizes UUR); MT-TL2 (tRNA-Leu, recognizes CUN); MT-ND1, MT-ND2, MT-ND5, and MT-ND6 (subunits 1, 2, 5, and 6, respectively, of NADH dehydrogenase); and MT-CYB (cytochrome b) were potentially associated with atherosclerosis. From 29% (2 of 7 aortic samples) upto 86% (6 of 7 aortic samples) of aortic samples had a significant difference between atherosclerotic plaques and unaffected tissue, with the respect to the level of heteroplasmy for each mutation. Further, the homogenates of affected and normal intimae of 22 aortas were compared to reveal the average level of heteroplasmy for the above-mentioned 10 mutations. For five mutations, the mean level of heteroplasmy was significantly different in atherosclerotic intimal homogenates in comparison with the unaffected tissue. These mutations were A1555G, C3256T, T3336C, G13513A, and G15059A. Thus, it was demonstrated that at least five mitochondrial mutations occurring in MT-RNR1, MT-TL1, MT-ND2, MT-ND5, and MT-CYB genes are associated with atherosclerosis.
authors.affiliation: Russian Cardiology Research and Production Complex, 121552 Moscow, Russia.
authors.forename: Igor A
authors.initials: IA
authors.lastname: Sobenin
authors.forename: Margarita A
authors.initials: MA
authors.lastname: Sazonova
authors.forename: Anton Y
authors.initials: AY
authors.lastname: Postnov
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Bobryshev
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Orekhov
mesh_terms: D000328:Adult; D000368:Aged; D001011:Aorta / Q000648:ultrastructure*; D001018:Aortic Diseases / Q000235:genetics* / Q000473:pathology; D045303:Cytochromes b / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D042967:Electron Transport Complex I / Q000235:genetics; D005260:Female; D050259:Genes, Mitochondrial; D054629:Genome, Mitochondrial; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics; D057093:Orphan Nuclear Receptors / Q000235:genetics; D058226:Plaque, Atherosclerotic / Q000235:genetics* / Q000473:pathology; D012335:RNA, Ribosomal / Q000235:genetics; D012343:RNA, Transfer / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; C403073:NR2E3 protein, human; D057093:Orphan Nuclear Receptors; D012335:RNA, Ribosomal; D018124:Receptors, Tumor Necrosis Factor; C117018:TL1 cytokine; D012343:RNA, Transfer; D045303:Cytochromes b; C481838:MT-ND5 protein, human; D009245:NADH Dehydrogenase; C521326:NADH dehydrogenase subunit 2, human; D042967:Electron Transport Complex I