title: Mitochondrial DNA variants can mediate methylation status of inflammation, angiogenesis and signaling genes.
abstract: Mitochondrial (mt) DNA can be classified into haplogroups representing different geographic and/or racial origins of populations. The H haplogroup is protective against age-related macular degeneration (AMD), while the J haplogroup is high risk for AMD. In the present study, we performed comparison analyses of human retinal cell cybrids, which possess identical nuclei, but mtDNA from subjects with either the H or J haplogroups, and demonstrate differences in total global methylation, and expression patterns for two genes related to acetylation and five genes related to methylation. Analyses revealed that untreated-H and -J cybrids have different expression levels for nuclear genes (CFH, EFEMP1, VEGFA and NFkB2). However, expression levels for these genes become equivalent after treatment with a methylation inhibitor, 5-aza-2'-deoxycytidine. Moreover, sequencing of the entire mtDNA suggests that differences in epigenetic status found in cybrids are likely due to single nucleotide polymorphisms (SNPs) within the haplogroup profiles rather than rare variants or private SNPs. In conclusion, our findings indicate that mtDNA variants can mediate methylation profiles and transcription for inflammation, angiogenesis and various signaling pathways, which are important in several common diseases.
authors.affiliation: Gavin Herbert Eye Institute and.
authors.forename: Shari R
authors.initials: SR
authors.lastname: Atilano
authors.affiliation: Gavin Herbert Eye Institute and.
authors.forename: Deepika
authors.initials: D
authors.lastname: Malik
authors.affiliation: Gavin Herbert Eye Institute and.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Chwa
authors.affiliation: Gavin Herbert Eye Institute and.
authors.forename: Javier
authors.initials: J
authors.lastname: Cáceres-Del-Carpio
authors.affiliation: Gavin Herbert Eye Institute and Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Anthony B
authors.initials: AB
authors.lastname: Nesburn
authors.affiliation: Retina-Vitreous Associates Medical Group, Beverly Hills, CA 90211, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Boyer
authors.affiliation: Gavin Herbert Eye Institute and.
authors.forename: Baruch D
authors.initials: BD
authors.lastname: Kuppermann
authors.affiliation: Tulane Center for Aging and Department of Medicine, Tulane University, New Orleans, LA 70118, USA and.
authors.forename: S Michal
authors.initials: SM
authors.lastname: Jazwinski
authors.affiliation: Tulane Center for Aging and Department of Medicine, Tulane University, New Orleans, LA 70118, USA and.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Miceli
authors.affiliation: Center of Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Wallace
authors.affiliation: Gavin Herbert Eye Institute and.
authors.forename: Nitin
authors.initials: N
authors.lastname: Udar
authors.affiliation: Gavin Herbert Eye Institute and Department of Pathology and Laboratory Medicine, University of California Irvine, Irvine, CA 92697, USA, mkenney@uci.edu.
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Kenney
mesh_terms: D002460:Cell Line; D019175:DNA Methylation / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D004365:Drugs, Chinese Herbal; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics; D008297:Male; D009389:Neovascularization, Pathologic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D004365:Drugs, Chinese Herbal; C569176:chan-yu-bao-yuan-tang