%0 Journal Article
%T Genomic Research to Identify Novel Pathways in the Development of Abdominal Aortic Aneurysm
%A Seamus C. Harrison
%A Anastasia Z. Kalea
%A Michael V. Holmes
%A Obi Agu
%A Steve E. Humphries
%J Cardiology Research and Practice
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/852829
%X Abdominal aortic aneurysm (AAA) is a common disease with a large heritable component. There is a need to improve our understanding of AAA pathogenesis in order to develop novel treatment paradigms. Genomewide association studies have revolutionized research into the genetic variants that underpin the development of many complex diseases including AAA. This article reviews the progress that has been made to date in this regard, including mechanisms by which loci identified by GWAS may contribute to the development of AAA. It also highlights potential post-GWAS analytical strategies to improve our understanding of the disease further. 1. Introduction Abdominal aortic aneurysm (AAA) is a common, late onset disease which, left untreated, can rupture with a high resultant mortality. Approximately 5% of Caucasian males aged 65¨C74 will harbor a AAA [1] and the major risk factors for the condition include male sex, cigarette smoking, a history of cardiovascular disease, and a family history of AAA [2, 3]. Currently, the best predictor of rupture is maximal aneurysm diameter and surgical repair is indicated in AAA greater than 5.5£¿cm [4]. Population screening with abdominal ultrasound scans (US) reduces the burden of aneurysm related death [5, 6], but there is a lack of evidence to support any pharmacological therapies to attenuate AAA progression and/or rupture. The advent of endovascular aneurysm repair has reduced short-term perioperative mortality associated with AAA repair [7] but nationwide audits indicate that elective repair still carries a mortality risk in region of 1.5¨C7% [8]. In patients deemed unfit for surgical repair ten-year survival is less than 25% [9]. Understanding the genetic architecture of the condition may provide a blueprint for uncovering novel pathobiological pathways and targets for nonsurgical treatments. The role that genetic factors play in the development of AAA has become increasingly prominent in recent years following Clifton¡¯s initial observation that the disease appeared to run in families [10]. Family history of AAA is an established risk factor for the disease, with male first-degree relatives of probands at approximately fourfold greater risk than the general population [11¨C13]. A twin-study of AAA has estimated the heritability to be as high as 70% [14], and familial studies have failed to demonstrate consistent modes of inheritance, suggesting that it is likely to be a complex disease [13, 15], resulting from a complicated network of environmental and genetic risk factors. There has been some progress in discovery of
%U http://www.hindawi.com/journals/crp/2012/852829/