R. Vissepo1, B. Shue2, J. Hinson3, D. Melzer4, J. E. Indes2 1University Of Connecticut School Of Medicine,Farmington, CT, USA 2University Of Connecticut Health Center,Department Of Surgery,Farmington, CT, USA 3University Of Connecticut Health Center,Department Of Cardiology,Farmington, CT, USA 4University Of Connecticut Health Center,Center On Aging,Farmington, CT, USA
Introduction: Abdominal aortic aneurysm (AAA) is a common medical condition that contains a genetic and inheritable component. A number of different genes, including genes of the extracellular matrix (ECM) and the immune system, have been identified and found to be associated with the development or progression of AAAs. The aim of this study was to create a database and characterize the influence of candidate genes to help describe the inherited component of AAA.
Methods: A systematic search of the PUBMED database using the search terms “AAA” and “Gene” was performed to identify candidate genes contributing to the etiology of abdominal aortic aneurysms. Inclusion criteria included single studies and review articles in which the focus was the association between genes and AAA. Exclusion criteria included duplicates, editorials, isolated animal studies and studies whose main focus was not the genetic component of AAA. The results from the studies were collected and analyzed in order to determine their quality. Genes were considered “strong” if the majority of the reviewed studies determined a genetic association with AAA. The genes in which the majority of the studies determined that no genetic association existed were considered “weak” genes. Genes placed in the “moderate” category only had one study or review article which showed a genetic association with AAA. The genes were gathered from genome-wide association studies and from genetic association studies, using sequence variants, on patients with AAA and controls.
Results: A total of 9 review articles and 12 studies were obtained from the systematic search. The search identified 96 gene candidates, including sequence variants. After assessment studies, the number of genes associated with abdominal aortic aneurysm amounted to 55 genes, while 41 genes were found to have no association with AAA. Of the genes that were considered to have an association with AAA, 1 was considered to have a strong association, cyclin-dependent kinase inhibitor 2B antisense RNA (CDKN2BAS), 22 genes were considered to have a moderate association, while 32 of the genes were considered to have a weak association. After an analysis of the different population sets associated with the strong candidate gene, CDKN2BAS, the relative risk was determined to be 1.143 (95% CI, 1.102-1.184).
Conclusion: The characterization of the genes that have known associations with AAA may be useful in future investigations in order to identify new genes and mechanisms in which abdominal aortic aneurysms occur. The identification of strong candidate genes, such as CDKN2BAS, may help guide studies on the inherited and genetic component of abdominal aortic aneurysms.