Current efforts to identify the genetic contribution to abdominal aortic aneurysm (AAA) have mainly focused on the assessment of germ-line variants such as single-nucleotide polymorphisms. The aim of the present study was to assess the presence of acquired chromosomal aberrations in human AAA. Microarray data of ten biopsies obtained from the site of main AAA dilatation (AAA body) and three control biopsies obtained from the macroscopically non-dilated neck of the AAA (AAA neck) were initially compared with identified chromosomal aneuploidies using the Chromosomal Aberration Region Miner (ChARM) software. A commonly deleted segment of chromosome bands 6 (q22.1-23.2) was predicted within AAA biopsies. This finding was confirmed by quantitative real-time PCR (qPCR)-based DNA copy number assessments of an independent set of six AAA body and neck biopsies which identified a fold copy number change (∆KCt) of −1±0.35, suggesting the loss of one copy of the long interspersed nucleotide element type 1 (LINE-1) mapped to chromosome 6 (q22.1-23.2). The median relative genomic content of LINE-1 DNA was also reduced in AAA body compared with AAA neck biopsies (1.540 compared with 3.159; P=0.031). A gene important for vascular homoeostasis mapped to 6q23.1, connective tissue growth factor (CTGF), was assessed and found to be significantly down-regulated within AAA bodies compared with AAA necks (0.261 compared with 0.627; P=0.031), as determined by reverse transcription qPCR using total RNA as a template. Histology demonstrated marked staining for macrophages within AAA body biopsies. We found in vitro that the median relative genomic content of LINE-1 DNA in aortic vascular smooth muscle cells (AoSMCs) exposed to pro-inflammatory medium was ~1.5 times greater than that measured in control AoSMCs exposed to non-conditioned medium (3.044 compared with 2.040; P=0.015). Our findings suggest that acquired chromosomal aberrations associated with retrotransposon propagation may predispose to sporadic AAA.
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Research Article|
June 17 2014
A deletion in chromosome 6q is associated with human abdominal aortic aneurysm
Erik Biros;
Erik Biros
*The Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia
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Corey S. Moran;
Corey S. Moran
*The Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia
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Philip J. Walker;
Philip J. Walker
†School of Medicine, Discipline of Surgery, and Centre for Clinical Research, University of Queensland, and Department of Vascular Surgery, Royal Brisbane and Women's Hospital, Herston, QLD 4029, Australia
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John Cardinal;
John Cardinal
‡Pathology Queensland Chemical Pathology, Royal Brisbane and Women's Hospital, Herston, QLD 4029, Australia
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Jonathan Golledge
*The Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia
§Department of Vascular and Endovascular Surgery, The Townsville Hospital, Townsville, QLD 4811, Australia
Correspondence: Professor Jonathan Golledge (email jonathan.golledge@jcu.edu.au).
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Publisher: Portland Press Ltd
Received:
November 28 2013
Revision Received:
March 10 2014
Accepted:
April 07 2014
Accepted Manuscript online:
April 07 2014
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2014 Biochemical Society
2014
Clin Sci (Lond) (2014) 127 (7): 475–484.
Article history
Received:
November 28 2013
Revision Received:
March 10 2014
Accepted:
April 07 2014
Accepted Manuscript online:
April 07 2014
Citation
Erik Biros, Corey S. Moran, Philip J. Walker, John Cardinal, Jonathan Golledge; A deletion in chromosome 6q is associated with human abdominal aortic aneurysm. Clin Sci (Lond) 1 October 2014; 127 (7): 475–484. doi: https://doi.org/10.1042/CS20130784
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