title: The potential role of DNA methylation in abdominal aortic aneurysms.
abstract: 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.
authors.affiliation: Department of Vascular and Endovascular Surgery, Geisinger Health System, Danville, PA 17822, USA. ejryer@geisinger.edu.
authors.forename: Evan J
authors.initials: EJ
authors.lastname: Ryer
authors.affiliation: Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA 17822, USA. peelert@susqu.edu.|Department of Biology, Susquehanna University, Selinsgrove, PA 17870, USA. peelert@susqu.edu.
authors.forename: Kaitryn E
authors.initials: KE
authors.lastname: Ronning
authors.affiliation: Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA 17822, USA. rerdman@geisinger.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Erdman
authors.affiliation: Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA 17822, USA. cmschworer@gmail.com.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Schworer
authors.affiliation: Department of Vascular and Endovascular Surgery, Geisinger Health System, Danville, PA 17822, USA. jelmore@geisinger.edu.
authors.forename: James R
authors.initials: JR
authors.lastname: Elmore
authors.affiliation: Department of Biology, Susquehanna University, Selinsgrove, PA 17870, USA. peelert@susqu.edu.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Peeler
authors.affiliation: Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA 17822, USA. cdnevius@geisinger.edu.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Nevius
authors.affiliation: Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI 48202, USA. johnlillvis@gmail.com.
authors.forename: John H
authors.initials: JH
authors.lastname: Lillvis
authors.affiliation: Department of Vascular and Endovascular Surgery, Geisinger Health System, Danville, PA 17822, USA. rpgarvin@geisinger.edu.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Garvin
authors.affiliation: Department of Vascular and Endovascular Surgery, Geisinger Health System, Danville, PA 17822, USA. dfranklin@geisinger.edu.
authors.forename: David P
authors.initials: DP
authors.lastname: Franklin
authors.affiliation: Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA 17822, USA. shkuivaniemi@geisinger.edu.|Department of Surgery, Temple University School of Medicine, Philadelphia, PA 19140, USA. shkuivaniemi@geisinger.edu.
authors.forename: Helena
authors.initials: H
authors.lastname: Kuivaniemi
authors.affiliation: Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA 17822, USA. gctromp@geisinger.edu.
authors.forename: Gerard
authors.initials: G
authors.lastname: Tromp
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018899:CpG Islands; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism; D019175:DNA Methylation; D006801:Humans; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011544:Pseudogenes / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015843:Serpins / Q000235:genetics / Q000378:metabolism; D012907:Smoking; D000096985:Calponins
chemical_list: D002135:Calcium-Binding Proteins; D004247:DNA; D008840:Microfilament Proteins; D015843:Serpins; D000096985:Calponins; C102316:SERPINB9 protein, human
keywords: AAA; ADCY10P1; CNN2; DNA methylation; KLHL35; SERPINB9; aortic aneurysm