Intracranial aneurysms (IAs) are thought to have a multifactorial origin. The authors undertook a comprehensive meta-analysis on all genes investigated using a case-control model in ruptured (subarachnoid hemorrhage) and unruptured aneurysms.
Electronic databases were searched until and including July 2008 for any candidate gene studied in IA or subarachnoid hemorrhage using a case-control model. The ORs and 95% CIs were determined for each gene-disease association using fixed and random effect models.
Thirty studies of 8 genes and 13 polymorphisms were analyzed among 19,961 individuals (6622 cases and 13,339 controls). Two genes and 3 polymorphisms were associated with IA. The eNOS gene T786C polymorphism (OR 1.24, 95% CI 1.0–1.54; p = 0.05) and IL-6 gene G572C polymorphism (OR 7.08, 95% CI 2.85–17.57; p < 0.0001) both showed a significant association with ruptured/unruptured IA. The IL-6/G174C polymorphism exerted a significant protective effect against IA (OR 0.49, 95% CI 0.25–0.95; p = 0.04). The other candidate genes investigated (ACE, endoglin, APOE, elastin, MMP-3, and SERPINA3) showed no significant associations.
There is a likely genetic basis to sporadic IAs. However, the evidence base is small when compared against other complex disorders.
Abbreviations used in this paper: eNOS = endothelial nitric oxide synthase; IA = intracranial aneurysm; IL-6 = interleukin-6; NO = nitric oxide; PAR = population-attributable risk; pHet = probability test for heterogeneity; SAH = subarachnoid hemorrhage; SNP = single nucleotide polymorphism.
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