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

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 current study was to assess the presence of acquired chromosomal aberrations in human AAA. Microarray data of 10 biopsies obtained from the site of main AAA dilatation (AAA body) and 3 control biopsies obtained from the macroscopically non-dilated neck of the AAA (AAA neck) were initially compared to identify chromosomal aneuploidies using the 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 (qPCR)-based DNA copy number assessments where a fold-copy number change (∆KCt) of -1±0.35 suggesting the loss of one copy of the long interspersed nucleotide elements (LINE-1) mapped to 6 (q22.1-23.2) was identified using DNA from an independent set of 6 AAA body compared to 6 paired AAA neck biopsies. The median relative genomic content of LINE-1 DNA was also reduced in AAA body compared to AAA neck biopsies (1.540 vs. 3.159, P=0.031). A gene important for vascular homeostasis mapped to 6q23.1, CTGF, was assessed and found to be significantly downregulated within AAA bodies compared to AAA necks (0.261 vs 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 bio...

Source: Clinical Science - April 7, 2014 Category: Biomedical Science Authors: E Biros, C S. Moran, P J. Walker, J Cardinal, J Golledge Source Type: research