Methylation profiling of DNA in the area of atherosclerotic plaque in humans |
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Authors: | M S Nazarenko V P Puzyrev I N Lebedev A V Frolov O L Barbarash L S Barbarash |
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Institution: | (1) Chair of Cardiology, “G. d’Annunzio” University, Chieti, and C.N.R. Institute of Clinical Physiology, Pisa;(2) Chair of Cardiology, “G. d’Annunzio” University, Chieti, and C.N.R. Institute of Clinical Physiology, Pisa, Lecce, Italy |
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Abstract: | Mutation theory of atherogenesis proved by “loss of heterozygosity” and microsatellite instability in the area of atherosclerotic
plaques is complemented by data on epigenetic variability of genetic loci involved in the pathologic process. However, only
recently large-scale analysis of epigenetic modifications in the human genome became possible. For the first time, the quantitative
microarray-based methylation profiling of 1505 CpG-sites in 807 genes was performed in atherosclerotic plaques of aorta and
carotid artery from humans using the GoldenGate Methylation Cancer Panel I (Illumina, United States). 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 located in CpG-island of the 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 the Human Genome Epidemiology Network (HuGENet), in which they were identified as candidates
for cardiovascular disease continuum. |
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