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Lancet Neurol. 2005 Mar;4(3):179-89.

Genetics of intracranial aneurysms.

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Department of Neurology, Rudolf Magnus Institute of Neuroscience, Utrecht, Netherlands. <>


Subarachnoid haemorrhage (SAH) is a subtype of stroke caused by the rupture of an intracranial aneurysm. Genetic factors play an important part in the pathogenesis of SAH and intracranial aneurysms. SAH and intracranial aneurysms are complex in origin, involving the interaction of several genes and environmental factors. A disruption of the extracellular matrix of the arterial wall, which provides strength and elasticity to intracranial arteries, is a likely factor in the pathophysiology of intracranial aneurysms. In this review, we discuss the genetic association, linkage, and gene-expression studies of SAH and intracranial aneurysms. At present, four genome-wide linkage studies have identified genetic loci for intracranial aneurysms. Interestingly, three of these loci include functional candidate genes coding for structural proteins of the extracellular matrix. Of these genes, elastin and collagen type 1A2 are the most promising candidates, because allelic association with intracranial aneurysms has also been shown for these genes. However, variation in these two genes only explains a small proportion of the genetic factors involved in intracranial aneurysms. Future studies need to identify new candidate genes to help unravel the pathophysiology of the disorder.

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