脳動脈瘤—遺伝子解析と治療薬開発の現状

Current Knowledge on the Genetic Analysis and Development of Medical Therapy for Intracranial Aneurysms

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・一塩基多型の解析では，複数の多型で脳動脈瘤との関連が示されている．そのため，脳動脈瘤は多因子疾患であると考えられる．

・脳動脈瘤多発家系や遺伝病において，細胞外基質や内皮細胞に関連する遺伝子などが原因遺伝子として同定されている．

・スタチン製剤やアスピリンの服用による脳動脈瘤破裂に起因するくも膜下出血発症抑制効果が臨床研究により示されている．

　Genetic studies on intracranial aneurysms（IAs）, like genome-wide association studies, or studies analyzing familial intracranial aneurysms, have successfully revealed the potential contribution of a set of genes to the pathology of IAs. Some of the genes may promote the formation of IAs or the process leading to rupture of the lesions through exacerbating inflammatory responses or facilitating the degenerative changes of arterial walls. Many genes or single-nucleotide polymorphisms have been identified through extensive analyses, but they can only explain one-fifth of the IA pathology; therefore, the pathogenesis of IAs is influenced by many factors, including environmental factors, and not only genetic ones. Intriguingly, a somatic mutation in the PDGFRB gene has recently been identified in more than half of the cases with fusiform aneurysms, making the development of medical therapy targeting PDGFRβ signaling realistic. Nowadays, following a series of recent experimental studies, IA is considered a chronic inflammatory disease affecting intracranial arteries, indicating the potential of anti-inflammatory drugs as therapeutic drugs for the treatment of IAs. No wonder, recently published observational studies have revealed the preventive effect of statins and aspirin, with potent anti-inflammatory effects on the rupture of IAs.