DNA METHYLATION STATUS OF THE CELL PROLIFERATION GENES IN ATHEROSCLEROSIS
M.S. Nazarenko, A.V. Markov, I.N. Lebedev, A.A. Sleptsov, A.V. Frolov, O.L. Barbarash, L.S. Barbarash, V.P. Puzyrev
Keywords: DNA methylation, atherosclerosis, Infinium HumanMethylation27 BeadChip
Abstract
The purpose of this study was to identify the features of methylation status of genes whose products are involved in the cell proliferation in vascular tissues of patients with atherosclerosis. We tested the vascular samples from carotid arteries, internal mammary arteries and saphenous veins, which differ in their morphological and functional characteristics and the degree of susceptibility to pathology. DNA methylation profiling was performed by using the microarray «Infinium HumanMethylation27 BeadChip» («Illumina», USA), methylation-sensitive polymerase chain reaction and methylation-specific PCR. For the first time we identified 45 CpG-sites of 36 genes with differential DNA methylation between vascular tissues. The most pronounced differences in the DNA methylation level were registered for CpG-dinucleotides of genes ALOX12, CARD11, DAB2IP, PTPRC, RASIP1, THRB, TLR4, TNFRSF9 and WNT16 . Our data do not support the hypothesis of epigenetic dysregulation of cell-cycle genes ( CDKN2A (p16INK4a and p14ARF), CDKN2B (p15INK4b)) in atherosclerosis.
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