The genetics of sporadic ruptured and unruptured intracranial aneurysms: a genetic meta-analysis of 8 genes and 13 polymorphisms in approximately 20,000 individuals.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
There is a likely genetic basis to sporadic IAs. However, the evidence base is small when compared against other complex disorders.
Imperial College Cerebrovascular Research Unit, Imperial College London, Hammersmith Hospitals, London, UK.
Peter
P
McColgan
Kyaw Zayar
KZ
Thant
Pankaj
P
Sharma
D017542:Aneurysm, Ruptured / Q000235:genetics*; D015703:Antigens, CD / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D030541:Databases, Genetic; D004549:Elastin / Q000235:genetics; D000071063:Endoglin; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D002532:Intracranial Aneurysm / Q000235:genetics*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics; D015843:Serpins / Q000235:genetics; D013345:Subarachnoid Hemorrhage / Q000235:genetics*
D015703:Antigens, CD; D001057:Apolipoproteins E; C064206:ENG protein, human; D000071063:Endoglin; C508600:IL6 protein, human; D015850:Interleukin-6; D011956:Receptors, Cell Surface; C516148:SERPINA3 protein, human; D015843:Serpins; D004549:Elastin; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A; D019278:Matrix Metalloproteinase 3