Genetic risk load according to the site of intracranial aneurysms

Abstract

Our findings suggest that genetic risk factors have a larger role in the development of IA at the MCA than at other sites, and that genetic heterogeneity should be considered in future genetic studies.

The Genetics of Aneurysms: A Complex Pathophysiology Requiring Complex Analysis

“…The combined Dutch and Finnish cohort described by van't Hof et al (7) and recently published in Neurology highlights the potential value of refined categorizations ( Table 1). This study selected for nearly 2000 saccular ICAs of the circle of Willis, paying particular attention to ICAs of the MCA territory, and sought associations with previously described SNPs and familial history of either aneurysms or subarachnoid hemorrhage.…”

“…Biopsy specimens were collected during surgical clipping of 8 ruptured aneurysms, 5 unruptured aneurysms, and 10 superficial temporal arteries. As in the study by van't Hoft et al (7), only saccular aneurysms were included to control for variability in expression that may be associated with morphologic phenotype. A combination of RNA sequencing and microarray analysis of previously described genes was performed (6).…”

“…A combination of RNA sequencing and microarray analysis of previously described genes was performed (6). As hypothesized, key genes related to macrophage mediated The combined Dutch and Finnish cohort described by van't Hof et al (7) and recently published in Neurology highlights the potential value of refined categorizations. SAH, subarachnoid hemorrhage; n/T, number of patients with characteristic/total number of patients with data on characteristic; IA, intracranial aneurysm; MCA, middle cerebral artery.…”

Intracranial Aneurysm Pathophysiology: To Bleed, or not To Bleed, That Is the Question

“…However, it did not consider other possible factors implicated in the mechanisms of sIA rupture and it was not validated in independent series of unruptured sIA. It was also supposed that the genetic profile could contribute to IA rupture susceptibility; emerging evidence, in fact, suggests that a positive family history represents the strongest known risk factor for SAH from ruptured IA, indicating that heritable DNA variation may influence IA susceptibility (6,21).…”

“…In 2008, a multicenter collaboration led to complete a multistage GWAS that identified common variants that contribute to IA formation in three large cohorts: a Finnish cohort of 920 cases and 985 controls, a Dutch cohort of 781 cases and 6424 controls and a Japanese cohort of 495 cases and 676 controls: common SNPs on chromosomes 2q, 8q and 9p were identified and showed significant association with IA (3). By candidate-gene and GWAS approaches, a strong association between IA risk and other 7 SNPs at 6 genetic loci encompassing the genes CDKN2B-AS, STARD13-KL, RBBP8, SOX17, CNNM2, and EDNRA were identified (1,21,26). It was hypothesized that implicated gene products might have a role in cell cycle progression, in the proliferation, senescence and differentiation of progenitor-cell populations, in vascular endothelial maintenance, integrity of the extracellular cellular matrix, and inflammation (18,26).…”