Atilano Shari R, Malik Deepika, Chwa Marilyn, Cáceres-Del-Carpio Javier, Nesburn Anthony B, Boyer David S, Kuppermann Baruch D, Jazwinski S Michal, Miceli Michael V, Wallace Douglas C, Udar Nitin, Kenney M Cristina
Gavin Herbert Eye Institute and.
Gavin Herbert Eye Institute and Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Hum Mol Genet. 2015 Aug 15;24(16):4491-503. doi: 10.1093/hmg/ddv173. Epub 2015 May 10.
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.
线粒体（mt）DNA可分为代表不同人群地理和/或种族起源的单倍群。H单倍群对年龄相关性黄斑变性（AMD）具有保护作用，而J单倍群患AMD的风险较高。在本研究中，我们对人视网膜细胞胞质杂种进行了比较分析，这些胞质杂种具有相同的细胞核，但分别含有来自H或J单倍群受试者的mtDNA，并证明了总体全基因组甲基化以及与乙酰化相关的两个基因和与甲基化相关的五个基因的表达模式存在差异。分析表明，未经处理的H和J胞质杂种的核基因（CFH、EFEMP1、VEGFA和NFkB2）表达水平不同。然而，在用甲基化抑制剂5-氮杂-2'-脱氧胞苷处理后，这些基因的表达水平变得相等。此外，对整个mtDNA的测序表明，在胞质杂种中发现的表观遗传状态差异可能是由于单倍群谱内的单核苷酸多态性（SNP），而非罕见变异或私有SNP。总之，我们的研究结果表明，mtDNA变异可介导炎症、血管生成和各种信号通路的甲基化谱及转录，而这些在几种常见疾病中都很重要。
