Researchers identify genetic variant associated with increased risk of AAA

Geisinger researchers are part of an international team that has identified a genetic variant more common in individuals with abdominal aortic aneurysms (AAA). This is one of the largest studies ever into the genetics of AAA. The results of the work will appear in this week's online edition of Nature Genetics (www.nature.com/ng)

Geisinger researchers Helena Kuivaniemi, M.D.; Gerard Tromp, Ph.D.; David J. Carey, Ph.D.; and James Elmore, M.D., say their team is on track to establish the genetic triggers for AAA. This finding will pave the way for earlier diagnosis of adults who could be at risk of developing the condition and open up the possibility of inventing new drugs and treatments.

AAA, the most common aneurysm, is a balloon-like protrusion in the abdomen's main artery (aorta) that, if untreated, is potentially life-threatening. Considered a significant national public health problem, AAA accounts for more than 150,000 hospital admissions, 40,000 repair operations and 15,000 deaths annually. The identification of this common genetic variant through the collaboration of researchers from Geisinger's Weis Center for Research with researchers at other centers in the United States, Europe and Canada will bring hope to many who believe that the propensity for AAA runs in their families.

"What is critical now is to expand and translate this basic biological finding into a clinical tool for early detection and treatment," said senior researcher Dr. Kuivanemi.

"Critical to Geisinger's role in this project," noted Dr. David Carey, "is MyCode™, a cohort of Geisinger patients who have consented to the use of their blood and DNA samples for research to elucidate the genetic basis of disease."

The identification of a genetic variant, called a SNP (pronounced snip), refers to a single nucleotide polymorphism on chromosome 9q33 that is associated with an increased risk of AAA. This SNP is located within the DAB2IP gene that encodes an inhibitor of cell growth and survival and is associated with early-onset myocardial infarction, peripheral arterial disease and pulmonary embolism, but not with intracranial aneurysm or ischemic stroke. No association was observed between the variant and common risk factors for arterial and venous diseases, such as smoking, lipid levels, obesity, type 2 diabetes and hypertension.

Drs. Kuivaniemi, Tromp, Carey and James Elmore have been studying AAA for more than 15 years and have co-authored several publications on the genetics of AAA.