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Int. J. Mol. Sci. 2015, 16(5), 11259-11275;

The Potential Role of DNA Methylation in Abdominal Aortic Aneurysms

Department of Vascular and Endovascular Surgery, Geisinger Health System, Danville, PA 17822, USA
Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA 17822, USA
Department of Biology, Susquehanna University, Selinsgrove, PA 17870, USA
Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI 48202, USA
Department of Surgery, Temple University School of Medicine, Philadelphia, PA 19140, USA
Author to whom correspondence should be addressed.
Academic Editors: Jonathan Golledge and Joseph V. Moxon
Received: 7 November 2014 / Accepted: 19 January 2015 / Published: 18 May 2015
(This article belongs to the Special Issue Advances in Peripheral Artery Disease)
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Abdominal aortic aneurysm (AAA) is a complex disorder that has a significant impact on the aging population. While both genetic and environmental risk factors have been implicated in AAA formation, the precise genetic markers involved and the factors influencing their expression remain an area of ongoing investigation. DNA methylation has been previously used to study gene silencing in other inflammatory disorders and since AAA has an extensive inflammatory component, we sought to examine the genome-wide DNA methylation profiles in mononuclear blood cells of AAA cases and matched non-AAA controls. To this end, we collected blood samples and isolated mononuclear cells for DNA and RNA extraction from four all male groups: AAA smokers (n = 11), AAA non-smokers (n = 9), control smokers (n = 10) and control non-smokers (n = 11). Methylation data were obtained using the Illumina 450k Human Methylation Bead Chip and analyzed using the R language and multiple Bioconductor packages. Principal component analysis and linear analysis of CpG island subsets identified four regions with significant differences in methylation with respect to AAA: kelch-like family member 35 (KLHL35), calponin 2 (CNN2), serpin peptidase inhibitor clade B (ovalbumin) member 9 (SERPINB9), and adenylate cyclase 10 pseudogene 1 (ADCY10P1). Follow-up studies included RT-PCR and immunostaining for CNN2 and SERPINB9. These findings are novel and suggest DNA methylation may play a role in AAA pathobiology. View Full-Text
Keywords: DNA methylation; AAA; KLHL35; CNN2; SERPINB9; ADCY10P1; aortic aneurysm DNA methylation; AAA; KLHL35; CNN2; SERPINB9; ADCY10P1; aortic aneurysm

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Ryer, E.J.; Ronning, K.E.; Erdman, R.; Schworer, C.M.; Elmore, J.R.; Peeler, T.C.; Nevius, C.D.; Lillvis, J.H.; Garvin, R.P.; Franklin, D.P.; Kuivaniemi, H.; Tromp, G. The Potential Role of DNA Methylation in Abdominal Aortic Aneurysms. Int. J. Mol. Sci. 2015, 16, 11259-11275.

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