Korean Circ J.  2011 Jul;41(7):385-393. 10.4070/kcj.2011.41.7.385.

Deoxyribonucleic Acid Copy Number Aberrations in Vasospastic Angina Patients Using an Array Comparative Genomic Hybridization

• Seo SM
• Koh YS
• Jung HO
• Choi JS
• Kim PJ
• Baek SH
• Youn HJ
• Lee KH
• Seung KB

• KMID: 2225102
• DOI: http://doi.org/10.4070/kcj.2011.41.7.385

Abstract

BACKGROUND AND OBJECTIVES
Vasospastic angina (VA) is a specific type of coronary artery disease and develops as a result of coronary artery spasm. Recently, a few studies have revealed that VA caused by coronary artery spasm is related to genetic traits. The objective of this study was to use the recently developed technique of array comparative genomic hybridization (CGH) to screen the genetic aberrations of VA.
SUBJECTS AND METHODS
To identify candidate genes that might be causally involved in the pathogenesis of VA, genomic deoxyribonucleic acids were extracted from whole blood of 28 patients with VA who presented at Department of Cardiology at Seoul St. Mary's Hospital, Seoul, Korea. The copy number profiles of these patients was then analyzed using array CGH and reverse transcriptase (RT) quantitative polymerase chain reaction (PCR).
RESULTS
Array CGH revealed gains in 31 different regions, with losses in the 4q35.2, 7q22.1, 10q26.3, 15q11.2, 16p13.11, 17p11.2 and 19q13.3 regions (more than 32% aberration in these regions). Several loci were found to be frequently including gains of 5p and 11q (50% of samples). The most common losses were found in 7q (54% of samples). Copy number aberrations in chromosomal regions were detected and corresponding genes were confirmed by RT quantitative PCR. The fold change levels were highest in the CTDP1 (18q23), HDAC10 (22q13.33), KCNQ1 (11p15.5-p15.4), NINJ2 (12p13.33), NOTCH2 (1p12-p11.2), PCSK6 (15q26.3), SDHA (5p15.33), and MUC17 (7q22.1) genes.
CONCLUSION
Many candidate chromosomal regions that might be related to the pathogenesis of VA were detected by array CGH and should be systematically investigated to establish the causative and specific genes for VA.

Keyword

Array comparative genomic hybridization; Vasospastic angina

MeSH Terms

Cardiology
Coat Protein Complex I
Comparative Genomic Hybridization
Coronary Artery Disease
Coronary Vessels
DNA
Humans
Korea
Polymerase Chain Reaction
RNA-Directed DNA Polymerase
Spasm
Coat Protein Complex I
DNA
RNA-Directed DNA Polymerase

Figure

• 

  Fig. 1 Array comparative genomic hybridization (CGH) results. Average log2 ratios (Y axis) of each chromosomal region at 1p, 5p, 7q, 11p, 12p, 15q, 18q and 22q (X axis) show differences in copy number in spasm patients. Internal control (XX/XY) was used to detect genomic imbalances. Note the high-level aberrations (arrowed spots) on chromosomes.

• 

  Fig. 2 Relative fold differences selected from 8 genes showed that the most frequent gains and losses detected were at 1p, 5p, 7q, 11p, 12p, 15q, 18q and 22q region. Each sample is depicted (X axis) and the fold difference of N-value was delineated in RT PCR (Y axis). A threshold level of 2 (N-value) indicates significant DNA gain (A-G), and 0.5 (N-value) indicates significant DNA loss (H). RT: reverse transcriptase, PCR: polymerase chain reaction, DNA: deoxyribonucleic acid.

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