Methylation Status of the Cell Cycle Control-Associated Genes in the Carotid Artery Tissue of Atherosclerotic patients
Abstract
Objective: We tested the hypothesis that the aberrant methylation of the promoters and first exons of CDKN2A (p16INK4a, p14ARF), CDKN2B (p15INK4b) and RB1 genes was associated with carotid atherosclerosis.
Methods and results: The DNA methylation status of these cell cycle control-associated genes was analysed in 120 samples of carotid arteries using two different techniques: methylationsensitive polymerase chain reaction (MS-PCR) and methylation-specific PCR (MSP-PCR). DNA methylation was not detected in advanced atherosclerotic plaques or nearby macroscopically intact tissues of the vascular wall from the same patients.
Conclusion: The methylation status of CDKN2A, CDKN2B and RB1 genes does not appear to be a marker of human carotid atherosclerosis.
About the Authors
M. S. NazarenkoRussian Federation
Maria S. Nazarenko, Ph.D
10 Ushaika Embankment, Tomsk, 634050
A. V. Markov
Russian Federation
Anton V. Markov
10 Ushaika Embankment, Tomsk, 634050
I. A. Koroleva
Russian Federation
Iuliia A. Koroleva ccccccc
10 Ushaika Embankment, Tomsk, 634050
I. N. Lebedev
Russian Federation
Igor N. Lebedev, Ph.D.
10 Ushaika Embankment, Tomsk, 634050
A. A. Sleptcov
Russian Federation
Alexei A. Sleptcov
10 Ushaika Embankment, Tomsk, 634050
A. V. Frolov
Russian Federation
Alexey V. Frolov, Ph.D.
6 Sosnovy Blvd, Kemerovo, 650002
O. L. Barbarash
Russian Federation
Olga L. Barbarash, Ph.D., MD
6 Sosnovy Blvd, Kemerovo, 650002
V. P. Puzyrev
Russian Federation
Valery P. Puzyrev Ph.D., MD
10 Ushaika Embankment, Tomsk, 634050
References
1. Abnormal methylation of some tumor suppressor genes at sporadic breast cancer / V. V. Zemliakova, A.I. Zhevlova, V.V. Strel’nikov [et al.] // Mol. Biol. – 2003. – V. 37, № 4. – P. 696- 703.
2. Amatya V.J. Methylation of p14(ARF) gene in meningiomas and its correlation to the p53 expression and mutation / V.J. Amatya, Y. Takeshima, K. Inai // Mod. Pathol. – 2004. – V. 17, № 6. – P. 705-710.
3. Baccarelli A. Cardiovascular epigenetics: basic concepts and results from animal and human studies / A. Baccarelli, M. Rienstra, E.J. Benjamin // Circ. Cardiovasc. Genet. – 2010. – V. 3. – № 6. – P. 567-573.
4. Control of cell proliferation in atherosclerosis: insights from animal models and human studies / J. J. Fuster, P. Fernandez, H. Gonzalez-Navarro [et al.] // Cardiovasc. Res. – 2010. – V. 86. – № 2. – P. 254-264.
5. DNA hypomethylation and methyltransferase expression in atherosclerotic lesions / M.O. Hiltunen, M.P. Turunen, T. P. Rutanen [et al.] // Vasc. Med. – 2002. – V. 7. – № 1. – P. 5-11.
6. Epigenetics and atherosclerosis / M.P. Turunen, E. Aavik, S. Yla-Herttuala // Biochim. Biophys. Acta. – 2009. – V. 1790, № 9. – P. 886- 891.
7. Epigenetic changes in estrogen receptor beta gene in atherosclerotic cardiovascular tissues and in-vitro vascular senescence / J. Kim, J.Y. Kim, K.S. Song [et al.] // Biochim. Biophys. Acta. – 2007. – V. 1772, № 1. – P. 72-80.
8. Extensive demethylation of normally hypermethylated CpG islands occurs in human atherosclerotic arteries / S.A. Castillo-Diaz, M.E. Garay-Sevilla, M.A. Hernandez-Gonzalez [et al.] // Int. J. Mol. Med. – 2010. – V. 26, № 5. – P. 691-700.
9. Holdt L.M. Recent studies of the human chromosome 9p21 locus, which is associated with atherosclerosis in human populations / L.M. Holdt, D. Teupser // Arterioscler. Thromb. Vasc. Biol. – 2012. – V. 32, № 2. – P. 196-206.
10. Macrophage retinoblastoma deficiency leads to enhanced atherosclerosis development in ApoE-deficient mice / L.S. Boesten, A.S. Zadelaar, A. Nieuwkoop [et al.] // FASEB. J. – 2006. – V. 20, № 7. – P. 953-955.
11. Methylation of the estrogen receptor gene is associated with aging and atherosclerosis in the cardiovascular system / W.S. Post, P.J. Goldschmidt-Clermont, C. C. Wilhide [et al.] // Cardiovasc. Res. – 1999. – V. 43, № 4. – P. 985- 991.
12. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands / J.G. Herman, J.R. Graff, S. Myohanen [et al.] // Proc. Natl. Acad. Sci. U.S.A. – 1996. – V. 93, №18. – P.9821-9826.
13. p19(ARF) deficiency reduces macrophage and vascular smooth muscle cell apoptosis and aggravates atherosclerosis / H. GonzalezNavarro, Y.N. Abu Nabah [et al.] // J. Am. Coll. Cardiol. – 2010. – V. 55, № 20. – P. 2258-2268.
14. Tissue factor pathway inhibitor-2 gene methylation is associated with low expression in carotid atherosclerotic plaques / C. Zawadzki, N. Chatelain, M. Delestre [et al.] // Atherosclerosis. – 2009. – V. 204, № 2. – P. e4-14.
15. Inactivation of monocarboxylate transporter MCT3 by DNA methylation in atherosclerosis / S. Zhu, P. J. Goldschmidt-Clermont, C. Dong // Circulation. – 2005. – V. 112, № 9. – P. 1353- 1361.
Review
For citations:
Nazarenko M.S., Markov A.V., Koroleva I.A., Lebedev I.N., Sleptcov A.A., Frolov A.V., Barbarash O.L., Puzyrev V.P. Methylation Status of the Cell Cycle Control-Associated Genes in the Carotid Artery Tissue of Atherosclerotic patients. Yakut Medical Journal. 2014;(2):61-63.