Towards An Understanding Of The Etiology Of Abdominal Aortic Aneurysms: Identification Of Genes Implicated In Aaa Risk And Development
type: CreativeWork
description: Abdominal aortic aneurysm (AAA) is a common disease for which mechanisms of formation are still not well understood. Despite a strong genetic component to AAA risk, specific risk alleles are still largely unidentified. AAA is also a localized disease with a majority occurring in the infrarenal abdominal aorta and is six times more common than aneurysms of the thoracic aorta. To determine whether risk alleles are present in functional positional candidate genes. we: 1. performed a genetic association study using DNA from AAA cases and controls in ten candidate genes and 2. performed exon sequencing on three genes with evidence of nominal association. To identify genes with regional expression in the aorta of potential relevance to AAA: 1. Illumina microarrays were used to perform a gene expression profiling of entire baboon aortas and 2. protein expression of one candidate gene, HOXA4, was examined in further detail. Single nucleotide polymorphisms in three positional candidate genes, CEBPG, PEPD and CD22, that had both functions relevant to AAA and expression in AAA tissue exhibited nominal association and further studied by DNA sequencing of exons. Sequence variants were identified in PEPD and CD22, but not CEPBG, but no sequence variants had predicted functional changes. Analysis of the gene expression profiles from whole length baboon aortas identified 26 genes that exhibited lengthwise expression changes along aorta, including three genes from the homeobox (HOX) family of transcription factors. Comparison of HOX gene transcripts between AAA and control abdominal aortic tissue identified ten HOX genes that were significantly downregulated in AAA tissue. The most significantly downregulated HOX gene, HOXA4, also exhibited spatial expression changes and was studied in human aortic tissue. IImmunohistochemical staining of sections of human aorta using an antibody directed against HOXA4 showed expression in all three histological layers of the aorta, primarily by end…
abstract: Abdominal aortic aneurysm (AAA) is a common disease for which mechanisms of formation are still not well understood. Despite a strong genetic component to AAA risk, specific risk alleles are still largely unidentified. AAA is also a localized disease with a majority occurring in the infrarenal abdominal aorta and is six times more common than aneurysms of the thoracic aorta. To determine whether risk alleles are present in functional positional candidate genes. we: 1. performed a genetic association study using DNA from AAA cases and controls in ten candidate genes and 2. performed exon sequencing on three genes with evidence of nominal association. To identify genes with regional expression in the aorta of potential relevance to AAA: 1. Illumina microarrays were used to perform a gene expression profiling of entire baboon aortas and 2. protein expression of one candidate gene, HOXA4, was examined in further detail. Single nucleotide polymorphisms in three positional candidate genes, CEBPG, PEPD and CD22, that had both functions relevant to AAA and expression in AAA tissue exhibited nominal association and further studied by DNA sequencing of exons. Sequence variants were identified in PEPD and CD22, but not CEPBG, but no sequence variants had predicted functional changes. Analysis of the gene expression profiles from whole length baboon aortas identified 26 genes that exhibited lengthwise expression changes along aorta, including three genes from the homeobox (HOX) family of transcription factors. Comparison of HOX gene transcripts between AAA and control abdominal aortic tissue identified ten HOX genes that were significantly downregulated in AAA tissue. The most significantly downregulated HOX gene, HOXA4, also exhibited spatial expression changes and was studied in human aortic tissue. IImmunohistochemical staining of sections of human aorta using an antibody directed against HOXA4 showed expression in all three histological layers of the aorta, primarily by end…
author: Lillvis, John Hunt
keywords: Abdominal Aortic Aneurysms, Genetic Association, Homeobox, Microarray, Vascular Disease, Genetics, Molecular Biology
date published: 2010-01-01T08:00:00Z
date modified: 2026-07-24T05:58:42Z
provider: Wayne State University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Wayne State University