Understanding the genetics of intracranial aneurysms: A primer.

The genetics of intracranial aneurysms is complex. Much work has been done looking at the extracellular matrix surrounding cerebral vasculature as well as the role of matrix metalloproteinases. This comprehensive review summarizes what is known to date about the important genetic components that predispose to aneurysm formation and critically discusses the published findings. We discuss promising pre-clinical models of aneurysm formation and subarachnoid hemorrhage, and highlight avenues for future discovery, while considering limitations in the research to date. This review will further serve as a comprehensive reference guide to understand the genetic underpinnings for aneurysm pathophysiology and act as a primer for further investigation.

Gene Expression in Intracranial Aneurysms-Comparison Analysis of Aneurysmal Walls and Extracranial Arteries with Real-Time Polymerase Chain Reaction and Immunohistochemistry.

BACKGROUND: This study was aimed at evaluating the gene expression levels of 4 genes in the intracranial aneurysm wall and comparing them with extracranial arteries. The analysis was done using real-time polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). Also, a correlation of the differential genetic expression was done with various patient clinical and radiologic factors. METHODS: The quantitative assessment of ribonucleic acid levels was done with RT-PCR and was validated with IHC. The genes studied were collagen 1A2 (COL1A2), tissue inhibitor of metalloproteinase 4 (TIMP4), cathepsin B (CTSB), and alpha-1 antitrypsin (α-1 AT). The analysis was done on 24 aneurysm sacs and superficial temporal/occipital artery samples from patients undergoing surgical clipping. RESULTS: The mean fold change of COL1A2 in the aneurysm sample was 8.89, that of TIMP4 was 10.16, that of CTSB was 1.02, and that of α-1 AT was 1.46 when compared with normal control vessel on PCR. On semiquantitative IHC, COL1A2 was 94.44%, α-1 AT was 77.8% overexpressed, CTSB was positive in 50%, and the expression of TIMP4 was 94.4% underexpressed in aneurysmal walls. There was no statistically significant correlation between patient profile and gene expression. CONCLUSIONS: On RT-PCR and IHC analysis, COL1A2 and α-1 AT were overexpressed, CTSB was marginally overexpressed, and TIMP4 had equivocal expression in the aneurysmal sac when compared with the normal extracranial vessel. This is the first study of its kind in the Indian population with the largest sample size on live human patients.