Molecular genetics of abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) is a common disorder and a major cause of death. Pathological processes involved in AAA formation include inflammation, proteolysis, angiogenesis and apoptosis. It has also a strong familial predisposition with linkage studies identifying chromosomes 19q13 and 4q31 as susceptible loci. AAA is likely to be a polygenic disorder. Aims The aims of this study were to carry out a whole transcriptome analysis in order to identify novel genes and pathways that are differentially expressed between aneurysmal (AAA), atheromatous (AOD) and normal (NA) aortic tissue and to confirm a set of these differentially expressed genes using quantitative real time polymerase chain reaction (qRT-PCR). Methods RNA samples were prepared from full thickness aortic walls obtained during open repair of AAA, aortic bypass for AOD and transplant patients for NA. The quality of the RNA was assessed using the Bioanalyzer 2100 (Agilent) and Nanodrop. RNA was then reverse transcribed to cDNA which was then hybridised to the Human Genome (HG) -U133 plus 2.0 microarray (Affymetrix) that interrogates the whole human genome. The robustness of the genearray was assessed using data output quality control as defined by Affymetrix. Statistical analysis was then carried out using the GeneSpring software. Genes were considered to be significantly differentiated if they had at least a two-fold change and a P-value < 0.05 following Benjamini-Hochberg multiple correction testing. Genes were then classified according to their molecular functions. A set of consistently differentially expressed genes were confirmed using qRT-PCR with Taqman probes on a larger sample size compared with the microarray experiment. All pathway and network analysis on the differentially expressed genes were conducted using MetaCore software Version 6.3 (GeneGo, Inc). Results A total of 3320 genes and 233 genes were differentially expressed when comparing AAA with NA and AAA with AOD respectively.

Name dc:type.qualificationname

Doctor of Medicine

Level dc:type.qualificationlevel

Doctoral Thesis

Grantor dc:publisher.institution

King's College London

Year dc:date.issued

2012

Author dc:creator

• Chinien, Ganessen

Advisors dc:contributor.advisor

• Smith, Alberto
• Waltham, Matthew

Language dc:language

eng

Identifier

oai:kclpure.kcl.ac.uk:studenttheses/e269485a-e71a-41a7-9a8e-ae40eb968dd4

OAI identifier oai:identifier

oai:kclpure.kcl.ac.uk:studenttheses/e269485a-e71a-41a7-9a8e-ae40eb968dd4