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London, United Kingdom 2013 Poster Session Red Cerebrovasc Dis 2013; 35 (suppl 3)1-854 435 281 Etiology of stroke and risk factors Association between APOE genotype and CAA related vasculopathic changes – collaborative meta-analysis K. Rannikmäe1, R.N. Kalaria2, S.M. Greenberg3, H.C. Chui4, F.A. Schmitt5, C.L.M. Sudlow6 Division of Clinical Neurosciences, University of Edinburgh, Edinburgh, UNITED KING-DOM1, Institute for Ageing and Health, Newcastle University, Newcastle, UNITED KINGDOM2, Department of Neurology, Massachusetts General Hospital, Boston, USA3, Department of Neurolo-gy, University of Southern California, Los Angeles, USA4, Sanders-Brown Center on Aging, Depart-ment of Neurology, University of Kentucky, Lexington, USA5, Division of Clinical Neurosciences, University of Edinburgh, Edinburgh, UNITED KINGDOM6 Background: Cerebral amyloid angiopathy (CAA) is associated with lobar intracerebral haemor-rhage (ICH). While both the e4 - and e2 - alleles of the apolipoprotein E gene (APOE) are associat-ed with lobar ICH, only the e4 - allele is associated with the presence versus absence of CAA. It has been proposed that APOE-e4 promotes vascular amyloid deposition, while APOE-e2 promotes se-vere CAA-related vasculopathic changes that cause vessel rupture and ICH. We aimed to assess the evidence for these APOE allele-specific effects with a collaborative meta-analysis. Methods: We comprehensively sought published studies with data on APOE genotype and histo-pathological assessment of post-mortem brains for CAA, including severe vasculopathy. We ob-tained unpublished data from these on CAA grade (Vonsattel scale) for all APOE genotypes. We as-sessed effects of e2+ and e4+ genotypes, calculating study-specific and pooled odds ratios (ORs). Results: We identified six eligible studies (543 participants). Meta-analysis of data from five stud-ies (353 participants with CAA) showed a significant association of e4+ versus e4- genotypes with severe versus moderate/mild CAA (OR 2.5, 95% CI 1.4 to 4.5, p=0.002) and a trend for an associ-ation between e4+ versus e4- genotypes with severe versus moderate CAA (OR 1.7, 95%CI 0.9 to 3.1, p=0.11). For e2+ versus e2- genotypes, there was a trend towards an association (severe versus moderate/mild: OR 2.3, 95%CI 0.5 to 11.3, p=0.3; severe versus moderate: OR 2.7, 95% CI 0.62 to 11.42, p=0.19), with wide confidence intervals due to the small number of participants. Associations with presence versus absence of CAA were consistent with results from previous studies. Conclusion: We could not confirm an association between APOE-e2 and severe CAA-related vascu-lopathy, but these data do not exclude a biologically meaningful association. Further work is needed to better understand the associations of APOE genotypes with CAA and the mechanisms underlying these. 282 Etiology of stroke and risk factors Update from the Biorepository to Establish the Aetiology of Sinovenous Thrombosis (BEAST) Consortium; exome-analysis of >600 cases of Cerebral Sinovenous Thrombosis T. Marjot1, P. Sharma2 on Behalf of the BEAST Consotium Imperial College London, London, UNITED KINGDOM1, Imperial College London, London, UNITED KINGDOM2 Background Cerebral sinovenous thrombosis (CVT) is a rare form of cerebrovascular disease that accounts for ~1% of all strokes. Previous meta-analysis of case-control studies has proven a genetic basis to CVT, with genes conferring a greater level of thrombosis risk in the cerebral venous circulation compared with the arterial circulation. So far investigation into CVT has used a candidate-gene ap-proach. We aimed to set up the Biorepository to Establish the Aeitiology of Sinovenous Thrombosis (BEAST) Consortium in order to complete exome analysis of DNA from CVT cases and controls. Methods Recognising that no one group would have sufficient material, an international consortium was established. Each collaborator retrospectively recalled CVT patients and consented for DNA to be contributed to the repository. Each sample was matched to an extensive proforma of phenotype data including demographics, clinical presentation, method of diagnosis, transient and permanent risk factors, treatment and disability. Samples were then transported centrally in preparation for exome analysis using the Illumina human exome chip. The preliminary data generated from >600 CVT cas-es will facilitate further expansion of the repository. Where exomic control data is not available from each site this will be obtained in collaboration with other international consortia. Results Eleven research groups from 8 different countries have contributed blood/DNA from 628 CVT pa-tients and 187 controls. All DNA has now been extracted from blood samples and results from se-quencing are pending. Conclusions To our knowledge the BEAST consortium have compiled the largest DANN repository of CVT to date. Exome chip analysis will enable a better understanding of genetic contribution to this disease. Furthermore, the wealth of phenotypic information collected will provide a global perspective to the epidemiology, clinical course and management of this complex condition. Collaborator Country Number of Cases Number of Control Ida Matinelli Italy 177 0 Jonathan Coutinho Netherlands 64 64 Turgut Tatlisumak  Finland 108 0 Vincent Thijs Belgium 43 0 Allessandro Pezzini Italy 26 26 Maurizio Margaglione Italy 25 25 Elvira Grandone Italy 55 55 Kostas Spengos Greece 7 0 Antonio Arauz Mexico 92 0 Pankaj Sharma UK 14 0 Jose Ferro Portugal 17 17 628 187


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