A deletion in chromosome 6q is associated with human abdominal aortic aneurysm

Biros, Erik, Moran, Corey S., Walker, Philip J., Cardinal, John and Golledge, Jonathan (2014) A deletion in chromosome 6q is associated with human abdominal aortic aneurysm. Clinical Science, 127 7: 475-484. doi:10.1042/CS20130784

Author Biros, Erik
Moran, Corey S.
Walker, Philip J.
Cardinal, John
Golledge, Jonathan
Title A deletion in chromosome 6q is associated with human abdominal aortic aneurysm
Journal name Clinical Science   Check publisher's open access policy
ISSN 0143-5221
Publication date 2014-10
Year available 2014
Sub-type Article (original research)
DOI 10.1042/CS20130784
Open Access Status
Volume 127
Issue 7
Start page 475
End page 484
Total pages 10
Place of publication London, United Kingdom
Publisher Portland Press
Collection year 2015
Language eng
Formatted abstract
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.
Keyword Abdominal aortic aneurysm
Chromosome aberration
Long interspersed nucleotide element (LINE)
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
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