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.
McColgan
Peter
P
Imperial College Cerebrovascular Research Unit, Imperial College London, Hammersmith Hospitals, London, UK.
Thant
Kyaw Zayar
KZ
Sharma
Pankaj
P
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