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. pp. 475-484.

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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 (ΔKCt) 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.

Item ID: 35136
Item Type: Article (Research - C1)
ISSN: 1470-8736
Keywords: abdominal aortic aneurysm, chromosome aberration, inflammation, long interspersed nucleotide element (LINE)
Funders: Queensland Government, National Health and Medical Research Council (NHMRC), National Heart Foundation of Australia (NHF), Townsville Private Practice Trust Fund
Projects and Grants: NHMRC grant No. 10000967, NHMRC grant No. 1019921, NHMRC grant No. 1020955, NHMRC grant No. 021416, NHF grant number G09B4339]
Date Deposited: 28 Aug 2014 04:50
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl Cardiovascular Diseases) @ 60%
06 BIOLOGICAL SCIENCES > 0604 Genetics > 060412 Quantitative Genetics (incl Disease and Trait Mapping Genetics) @ 20%
11 MEDICAL AND HEALTH SCIENCES > 1116 Medical Physiology > 111699 Medical Physiology not elsewhere classified @ 20%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 100%
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