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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EA genome wide genotyping study has identified genetic loci that contribute to intracranial aneurysm (IA) formation and rupture. Single nucleotide polymorphisms on chromosomes 2q, 8q, and 9p showed significant association with IA [Bilguvar et al. \u003Cem\u003ENat Genet\u003C\/em\u003E 2008]. This article discusses the locus\u0027 association with coronary artery disease and, more recently, with aortic aneurysm and IA.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ENeurology Genomics\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EIschemia Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EA genome wide genotyping study has identified genetic loci that contribute to intracranial aneurysm (IA) formation and rupture. Single nucleotide polymorphisms (SNPs) on chromosomes 2q, 8q, and 9p showed significant association with IA (p values ranging from 10\u003Csup\u003E-8\u003C\/sup\u003E to 10\u003Csup\u003E-10\u003C\/sup\u003E and odds ratios 1.24 to 1.36) [Bilguvar et al. \u003Cem\u003ENat Genet\u003C\/em\u003E 2008]. Murat Gunel, MD, Yale University School of Medicine, New Haven, CT, reported that 2 of the loci, 2q and 8q, are novel, while the 9p locus previously has been associated with coronary artery disease and, more recently, with aortic aneurysm and IA.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EIA affects 2% to 5% of the population and commonly occurs between the ages of 40 and 60 years, typically with no antecedent event or warning. There is no reliable way to identify at-risk individuals. Genetic identification of these subjects would make it possible to identify individuals before an IA rupture for preventive treatment. The etiology and pathogenesis of intracranial aneurysms clearly are multifactorial, wherein genetic factors play an increasingly recognized role. First-degree relatives of patients with aneurysmal subarachnoid hemorrhage have a 4-fold increased risk of suffering a ruptured intracranial aneurysm compared with the general population [Schievink WI. \u003Cem\u003ENeurosurgery\u003C\/em\u003E 1997].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThis Genome Wide Association Study (GWAS) of IA was performed in over 10,000 subjects with Finnish, Dutch, and Japanese cohorts. In the European cohort, a significant association between chromosome 2 and IA was seen from 197.7 Mb to 198.6 Mb, while the association in the Japanese cohort was confined to SNPs in the more telomeric block (198.2 Mb to 198.5 Mb). The locus PLCL1 gene on chromosome 2 association interval is of special interest, because it has significant homology to phospholipase C which lies in a major signaling pathway that is important in CNS angiogenesis downstream of VEGFR2 [Shibuya M. J \u003Cem\u003EBiochem Mol Bio\u003C\/em\u003E 2006], which is a marker of endothelial progenitor cells and has been shown to play a role in CNS angiogenesis [Ziegler BL et al. \u003Cem\u003EScience\u003C\/em\u003E 1999]. Chromosome 8 association interval is much smaller and includes a single gene, \u003Cem\u003ESOX17\u003C\/em\u003E, which is essential for the specification and maintenance of the endoderm in the embryo [Hudson C et al. \u003Cem\u003ECell\u003C\/em\u003E 1997]. Post-natally, it is expressed in the endothelial cells and knock-out models in mice reveal significant vascular abnormalities, including defective endothelial sprouting and vascular remodeling [Matsui TJ. \u003Cem\u003ECell Sci\u003C\/em\u003E 2006].\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EBased on the results of this study, the authors hypothesize that IA might be due to defective development and\/or failure of the repair of the vasculature through the progenitor cell populations. Vascular injury mobilizes bone marrow or potentially vascular wall-derived progenitor\/stem cells to localize to sites of damage and that appear to be important in the repair process [Purhonen S et al. \u003Cem\u003EProc Natl Acad Sci\u003C\/em\u003E 2008]. IA genes might be involved in maintenance of these progenitor cells and the vascular repair process, such that the risk alleles identified in IA patients might result in less effective repair which ultimately leads to formation and rupture of aneurysms.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EThis is the first study to provide a means of identifying at-risk IA individuals preclinically, in which the risk of IA increases more than 3-fold in subjects with all 6 risk alleles compared with those who have none. Because these IA loci accounted for less than 2.3% to 3.8% of the genetic variance, additional common variants are highly likely to play a role in IA. Further studies are underway, using additional cohorts to identify additional loci.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2009 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/9\/1\/12.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzml42\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}