Identification of genomic aberrations by array comparative genomic hybridization in patients with aortic dissections

Abstract

Background: The aim of the present study was to identify chromosomal loci that contribute to the pathogenesis of aortic dissection (AD) in a Korean population using array comparative genomic hybridization (CGH) and to confirm the results using real-time polymerase chain reaction (PCR).

Materials and methods: Eighteen patients with ADs were enrolled in this study. Genomic DNA was extracted from individual blood samples, and array CGH analyses were performed. Four corresponding genes with obvious genomic changes were analyzed using real-time PCR in order to assess the level of genomic imbalance identified by array CGH.

Results: Genomic gains were most frequently detected at 8q24.3 (56%), followed by regions 7q35, 11q12.2, and 15q25.2 (50%). Genomic losses were most frequently observed at 4q35.2 (56%). Real-time PCR confirmed the results of the array CGH studies of the COL6A2, DGCR14, PCSK6, and SDHA genes.

Conclusion: This is the first study to identify candidate regions by array CGH in patients with ADs. The identification of genes that may predispose an individual to AD may lead to a better understanding of the mechanism of AD formation. Further multicenter studies comparing cohorts of patients of different ethnicities are warranted.

Keywords: Aorta; Aortic dissection; Genes; Polymerase chain reaction.

Fig. 1

Relative fold differences selected from 4 genes in which the most frequent gains and losses detected were in the 5p, 15q, 21q, and 22q regions. Each sample is depicted (x axis), and the fold difference of the N-value was delineated in real-time PCR (y axis). A threshold level of 2 indicates significant DNA gain (A~C), and 0.5 indicates significant DNA loss (D). At the chromosomal 21q22.3 location, COL6A2 (A), the fold change of the sample was 2.25- to 3.14-fold (seven samples) versus 1-fold for the reference sample. The fold difference for the SDHA (B) was 2.4- to 4.57-fold (six samples). For the PCSK6 (C), in the chromosomal 15q26.3 region, the fold change of the sample was 2.11- to 4.76-fold (six samples) with a gain at the location. Finally, DGCR14 (D) had a 0.08~0.4-fold change (seven samples) with a loss at the location (p<0.05).