The Potential Role of DNA Methylation in Abdominal Aortic Aneurysms
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 on...
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MDPI
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463699/ |
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pubmed-44636992015-06-16 The Potential Role of DNA Methylation in Abdominal Aortic Aneurysms Ryer, Evan J. Ronning, Kaitryn E. Erdman, Robert Schworer, Charles M. Elmore, James R. Peeler, Thomas C. Nevius, Christopher D. Lillvis, John H. Garvin, Robert P. Franklin, David P. Kuivaniemi, Helena Tromp, Gerard Article 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. MDPI 2015-05-18 /pmc/articles/PMC4463699/ /pubmed/25993294 http://dx.doi.org/10.3390/ijms160511259 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Ryer, Evan J. Ronning, Kaitryn E. Erdman, Robert Schworer, Charles M. Elmore, James R. Peeler, Thomas C. Nevius, Christopher D. Lillvis, John H. Garvin, Robert P. Franklin, David P. Kuivaniemi, Helena Tromp, Gerard |
| spellingShingle |
Ryer, Evan J. Ronning, Kaitryn E. Erdman, Robert Schworer, Charles M. Elmore, James R. Peeler, Thomas C. Nevius, Christopher D. Lillvis, John H. Garvin, Robert P. Franklin, David P. Kuivaniemi, Helena Tromp, Gerard The Potential Role of DNA Methylation in Abdominal Aortic Aneurysms |
| author_facet |
Ryer, Evan J. Ronning, Kaitryn E. Erdman, Robert Schworer, Charles M. Elmore, James R. Peeler, Thomas C. Nevius, Christopher D. Lillvis, John H. Garvin, Robert P. Franklin, David P. Kuivaniemi, Helena Tromp, Gerard |
| author_sort |
Ryer, Evan J. |
| title |
The Potential Role of DNA Methylation in Abdominal Aortic Aneurysms |
| title_short |
The Potential Role of DNA Methylation in Abdominal Aortic Aneurysms |
| title_full |
The Potential Role of DNA Methylation in Abdominal Aortic Aneurysms |
| title_fullStr |
The Potential Role of DNA Methylation in Abdominal Aortic Aneurysms |
| title_full_unstemmed |
The Potential Role of DNA Methylation in Abdominal Aortic Aneurysms |
| title_sort |
potential role of dna methylation in abdominal aortic aneurysms |
| description |
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. |
| publisher |
MDPI |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4463699/ |
| _version_ |
1613234402725199872 |