Nazarenko M S, Puzyrev V P, Lebedev I N, Frolov A V, Barbarash O L, Barbarash L S
Mol Biol (Mosk). 2011 Jul-Aug;45(4):610-6.
Somatic mutation theory of atherogenesis proved by alterations at the DNA level such as "loss of heterozygosity" and microsatellite instability in atherosclerotic plaque is complemented by the date of epigenetic variability of genetic loci involved in the pathological process. However, only recently large-scale analysis of epigenetic modifications in the human genome became possible. For the first time quantitative microarray-based methylation profiling of 1505 CpG-sites across 807 genes was performed in atherosclerotic aorta and carotid artery wall lesions using the GoldenGate Methylation Cancer Panel I ("Illumina", USA). One hundred and three (7%) CpG-sites in 90 (11%) genes were differentially methylated between tissue samples. The most pronounced differences in DNA methylation levels were registered for a site which is located in CpG-island of imprinted gene H19. By comparing 90 genes that were differentially methylated between tissue samples in our study, 10 genes (ICAM1, GSTM1, IGFBP1, POMC, APOA1, IL1RN, INS, LTA, MMP3, THBS2) were overlapped with data in Human Genome Epidemiology Network (HuGENet), in which they were identified as candidates for cardiovascular disease continuum.
动脉粥样硬化发生的体细胞突变理论通过DNA水平的改变得以证明，比如动脉粥样硬化斑块中的“杂合性缺失”和微卫星不稳定性，参与病理过程的基因位点的表观遗传变异性数据对该理论起到了补充作用。然而，直到最近对人类基因组表观遗传修饰进行大规模分析才成为可能。首次使用金门甲基化癌症检测板I（美国“Illumina”公司），对动脉粥样硬化主动脉和颈动脉壁病变中807个基因的1505个CpG位点进行了基于微阵列的定量甲基化分析。组织样本之间有90个（11%）基因中的103个（7%）CpG位点发生了差异甲基化。DNA甲基化水平最显著的差异出现在位于印记基因H19的CpG岛中的一个位点。通过比较我们研究中组织样本之间差异甲基化的90个基因，有10个基因（ICAM1、GSTM1、IGFBP1、POMC、APOA1、IL1RN、INS、LTA、MMP3、THBS2）与人类基因组流行病学网络（HuGENet）中的数据重叠，在该网络中它们被确定为心血管疾病连续体的候选基因。
