Abdominal aortic aneurysms - A complex genetic disease

Abdominal aortic aneurysms (AAAs) are a complex disease with a late age at onset. Causing approximately 15,000 deaths per year, AAAs are among the top twenty leading causes of death in the United States. A main reason for the high mortality rate of AAAs is that most are asymptomatic until rupture. Local inflammation of the aorta, fragmentation of the extracellular matrix and loss of smooth muscle cells are distinct characteristics of AAA formation. Large epidemiological studies have shown that smoking and positive family history are the two most important risk factors for AAAs. Other risk factors include male sex, increasing age, hypertension and high cholesterol. Interestingly, diabetes has a negative association with AAA. A genome-wide approach using DNA linkage analysis has found susceptibility loci for AAAs on chromosomes 19q13 and 4q31 and a genetic association study identified a variant on chromosome 9p21 associated with AAA in addition to other vascular phenotypes. Microarray-based expression profiles have also been generated to determine differentially expressed genes between AAA tissue and non-aneurysmal controls. These genetic and genomic approaches will be critical in determining the pathophysiological mechanisms leading to AAA formation, growth and rupture, and identifying the genetic factors predisposing to AAA later in life.