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International Journal of Molecular Medicine
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Article

Identification of hypo- and hypermethylated genes related to atherosclerosis by a genome-wide analysis of DNA methylation

  • Authors:
    • Yoshiji Yamada
    • Tamotsu Nishida
    • Hideki Horibe
    • Mitsutoshi Oguri
    • Kimihiko Kato
    • Motoji Sawabe
  • View Affiliations / Copyright

    Affiliations: Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie, Japan, Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Gifu, Japan, Department of Cardiology, Japanese Red Cross Nagoya First Hospital, Nagoya, Aichi, Japan, Section of Molecular Pathology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan
  • Pages: 1355-1340
    |
    Published online on: March 10, 2014
       https://doi.org/10.3892/ijmm.2014.1692
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Abstract

Epigenetic modification, particularly changes in DNA methylation at gene promoters, is implicated in the pathogenesis of atherosclerosis. However, the analysis of DNA methylation in atherosclerosis has been limited to a few selected candidate genes. In this study, we therefore performed a genome-wide analysis of DNA methylation in the atherosclerotic human aorta. A total of 48 post-mortem human aortic intima specimens were examined. To avoid the effects of interindividual variation, we performed intraindividual paired comparisons between atheromatous plaque lesions and corresponding plaque-free tissue for 24 subjects. Bisulfite-modified genomic DNA was analyzed for DNA methylation with a specific microarray (Illumina HumanMethylation450 BeadChip). We compensated for multiple comparisons by applying Bonferroni's correction for statistical significance of association. DNA methylation was significantly (P<1.03x10-7) reduced at 15 CpG sites in 14 genes and increased at 30 CpG sites in 22 genes in atheromatous plaque compared with plaque-free intima. Three of the hypomethylated genes [Drosophila headcase (HECA), early B-cell factor 1 (EBF1) and nucleotide-binding oligomerization domain containing 2 (NOD2)] and three of the hypermethylated genes [human mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), zinc finger E-box binding homeobox 1 (ZEB1) and FYN] were previously been implicated in atherosclerosis. The overexpression of HECA, EBF1 or NOD2 or the suppression of MAP4K4, ZEB1 or FYN expression in cultured HEK293 cells resulted in significant (P<4.80x10-7) changes in the expression of atherosclerosis-related genes, as determined with an expression microarray (Illumina HumanHT-12 v4 Expression BeadChip). Our findings suggested that HECA, EBF1 and NOD2 were significantly hypomethylated, whereas MAP4K4, ZEB1 and FYN were hypermethylated, in atheromatous plaque lesions compared with plaque-free intima. Epigenetic mechanisms may thus contribute to the pathogenesis of atherosclerosis.
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1 

Tsai PC, Spector TD and Bell JT: Using epigenome-wide association scans of DNA methylation in age-related complex human traits. Epigenomics. 4:511–526. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Rakyan VK, Down TA, Balding DJ and Beck S: Epigenome-wide association studies for common human diseases. Nat Rev Genet. 12:529–541. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Handy DE, Castro R and Loscalzo J: Epigenetic modifications: basic mechanisms and role in cardiovascular disease. Circulation. 123:2145–2156. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Turunen MP, Aavik E and Ylä-Herttuala S: Epigenetics and atherosclerosis. Biochim Biophys Acta. 1790:886–891. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Talens RP, Jukema JW, Trompet S, et al: Hypermethylation at loci sensitive to the prenatal environment is associated with increased incidence of myocardial infarction. Int J Epidemiol. 41:106–115. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Castillo-Díaz SA, Garay-Sevilla ME, Hernández-González MA, Solís-Martínez MO and Zaina S: Extensive demethylation of normally hypermethylated CpG islands occurs in human atherosclerotic arteries. Int J Mol Med. 26:691–700. 2010.PubMed/NCBI

7 

Bibikova M, Barnes B, Tsan C, et al: High density DNA methylation array with single CpG site resolution. Genomics. 98:288–295. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Sandoval J, Heyn H, Moran S, et al: Validation of a DNA methylation microarray for 450,000 CpG sites in the human genome. Epigenetics. 6:692–702. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Durocher Y, Perret S and Kamen A: High-level and high-throughput recombinant protein production by transient transfection of suspension-growing human 293-EBNA1 cells. Nucleic Acids Res. 30:E92002. View Article : Google Scholar

10 

Hägg S, Skogsberg J, Lundström J, et al: Multi-organ expression profiling uncovers a gene module in coronary artery disease involving transendothelial migration of leukocytes and LIM domain binding 2: the Stockholm Atherosclerosis Gene Expression (STAGE) study. PLoS Genet. 5:e10007542009.

11 

Nolan DK, Sutton B, Haynes C, et al: Fine mapping of a linkage peak with integration of lipid traits identifies novel coronary artery disease genes on chromosome 5. BMC Genet. 13:122012. View Article : Google Scholar : PubMed/NCBI

12 

Galluzzo S, Patti G, Dicuonzo G, et al: Association between NOD2/CARD15 polymorphisms and coronary artery disease: a case-control study. Hum Immunol. 72:636–640. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Miller VM, Petterson TM, Jeavons EN, et al: Genetic polymorphisms associated with carotid artery intima-media thickness and coronary artery calcification in women of the Kronos Early Estrogen Prevention Study. Physiol Genomics. 45:79–88. 2013. View Article : Google Scholar

14 

Reddy MA, Jin W, Villeneuve L, et al: Pro-inflammatory role of microRNA-200 in vascular smooth muscle cells from diabetic mice. Arterioscler Thromb Vasc Biol. 32:721–729. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Chen K, Li W, Major J, Rahaman SO, Febbraio M and Silverstein RL: Vav guanine nucleotide exchange factors link hyperlipidemia and a prothrombotic state. Blood. 117:5744–5750. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Dowejko A, Bauer RJ, Müller-Richter UD and Reichert TE: The human homolog of the Drosophila headcase protein slows down cell division of head and neck cancer cells. Carcinogenesis. 30:1678–1685. 2009.PubMed/NCBI

17 

Fantidis P: The role of intracellular 3′5′-cyclic adenosine monophosphate (cAMP) in atherosclerosis. Curr Vasc Pharmacol. 8:464–472. 2010.

18 

CARDIoGRAMplusC4D Consortium. Deloukas P, Kanoni S, Willenborg C, et al: Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet. 45:25–33. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Lukin K, Fields S, Hartley J and Hagman J: Early B cell factor: regulator of B lineage specification and commitment. Semin Immunol. 20:221–227. 2008. View Article : Google Scholar

20 

Fretz JA, Nelson T, Xi Y, Adams DJ, Rosen CJ and Horowitz MC: Altered metabolism and lipodystrophy in the early B-cell factor 1-deficient mouse. Endocrinology. 151:1611–1621. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Akerblad P, Lind U, Liberg D, Bamberg K and Sigvardsson M: Early B-cell factor (O/E-1) is a promoter of adipogenesis and involved in control of genes important for terminal adipocyte differentiation. Mol Cell Biol. 22:8015–8025. 2002. View Article : Google Scholar : PubMed/NCBI

22 

Opitz B, Förster S, Hocke AC, et al: Nod1-mediated endothelial cell activation by Chlamydophila pneumoniae. Circ Res. 96:319–326. 2005. View Article : Google Scholar : PubMed/NCBI

23 

Girardin SE, Boneca IG, Viala J, et al: Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem. 278:8869–8872. 2003. View Article : Google Scholar : PubMed/NCBI

24 

Inohara N, Koseki T, Lin J, et al: An induced proximity model for NF-kappa B activation in the Nod1/RICK and RIP signaling pathways. J Biol Chem. 275:27823–27831. 2000.PubMed/NCBI

25 

Collins T and Cybulsky MI: NF-κB: pivotal mediator or innocent bystander in atherogenesis? J Clin Invest. 107:255–264. 2001.

26 

Vandewalle C, Van Roy F and Berx G: The role of the ZEB family of transcription factors in development and disease. Cell Mol Life Sci. 66:773–787. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Davies MN, Volta M, Pidsley R, et al: Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood. Genome Biol. 13:R432012. View Article : Google Scholar : PubMed/NCBI

28 

Christensen BC, Houseman EA, Marsit CJ, et al: Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet. 5:e10006022009. View Article : Google Scholar : PubMed/NCBI

29 

Bell JT, Pai AA, Pickrell JK, et al: DNA methylation patterns associate with genetic and gene expression variation in HapMap cell lines. Genome Biol. 12:R102011. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yamada Y, Nishida T, Horibe H, Oguri M, Kato K and Sawabe M: Identification of hypo- and hypermethylated genes related to atherosclerosis by a genome-wide analysis of DNA methylation. Int J Mol Med 33: 1355-1340, 2014.
APA
Yamada, Y., Nishida, T., Horibe, H., Oguri, M., Kato, K., & Sawabe, M. (2014). Identification of hypo- and hypermethylated genes related to atherosclerosis by a genome-wide analysis of DNA methylation. International Journal of Molecular Medicine, 33, 1355-1340. https://doi.org/10.3892/ijmm.2014.1692
MLA
Yamada, Y., Nishida, T., Horibe, H., Oguri, M., Kato, K., Sawabe, M."Identification of hypo- and hypermethylated genes related to atherosclerosis by a genome-wide analysis of DNA methylation". International Journal of Molecular Medicine 33.5 (2014): 1355-1340.
Chicago
Yamada, Y., Nishida, T., Horibe, H., Oguri, M., Kato, K., Sawabe, M."Identification of hypo- and hypermethylated genes related to atherosclerosis by a genome-wide analysis of DNA methylation". International Journal of Molecular Medicine 33, no. 5 (2014): 1355-1340. https://doi.org/10.3892/ijmm.2014.1692
Copy and paste a formatted citation
x
Spandidos Publications style
Yamada Y, Nishida T, Horibe H, Oguri M, Kato K and Sawabe M: Identification of hypo- and hypermethylated genes related to atherosclerosis by a genome-wide analysis of DNA methylation. Int J Mol Med 33: 1355-1340, 2014.
APA
Yamada, Y., Nishida, T., Horibe, H., Oguri, M., Kato, K., & Sawabe, M. (2014). Identification of hypo- and hypermethylated genes related to atherosclerosis by a genome-wide analysis of DNA methylation. International Journal of Molecular Medicine, 33, 1355-1340. https://doi.org/10.3892/ijmm.2014.1692
MLA
Yamada, Y., Nishida, T., Horibe, H., Oguri, M., Kato, K., Sawabe, M."Identification of hypo- and hypermethylated genes related to atherosclerosis by a genome-wide analysis of DNA methylation". International Journal of Molecular Medicine 33.5 (2014): 1355-1340.
Chicago
Yamada, Y., Nishida, T., Horibe, H., Oguri, M., Kato, K., Sawabe, M."Identification of hypo- and hypermethylated genes related to atherosclerosis by a genome-wide analysis of DNA methylation". International Journal of Molecular Medicine 33, no. 5 (2014): 1355-1340. https://doi.org/10.3892/ijmm.2014.1692
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