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Abstract Details

The Association of SUR1 Polymorphisms with Acute Infarct Size: The MRI-GENIE Study
Cerebrovascular Disease and Interventional Neurology
S60 - Cerebrovascular Imaging and Biomarkers (2:36 PM-2:48 PM)
009
To determine whether polymorphisms of the ABCC8 gene which encodes SUR1 are associated with acute infarct size in non-lacunar strokes.
Sulfonylurea receptor 1 (SUR1) is a key ion channel regulator involved in cerebral edema (CE) in large ischemic strokes. Sulfonylurea drugs, which inhibit SUR1, have demonstrated promising results in reducing edema in this setting, though the role of SUR1 in smaller non-lacunar strokes has not been elucidated. Importantly, ABCC8 polymorphisms found in key structural regions of SUR1 have been associated with CE and clinical outcomes in severe traumatic brain injury.
A repository of MRIs of acute ischemic stroke patients enrolled through 12 international sites in the MRI-GENIE study was used to obtain automated diffusion-weighted imaging (DWI) lesion size and genotype data. A multivariate linear regression model with allelic dose of the 4 different ABCC8 tag SNPs (rs7105832, rs2237982, rs11024286, rs4148622) adjusted for age, sex and population stratification with log DWI volume was performed. 
The final analysis included 2094 subjects with 0, 1 or 2 copies of alleles for SNPs rs7105832, rs2237982 and rs4148622, and 2035 subjects for the SNP rs11024286. Both rs7105832 and rs2237982 demonstrate a nonsignificant trend towards association with decreased log DWI (p= 0.053, 0.078 respectively); rs110024286 and rs4148622 SNPs demonstrate no association with log DWI (p=0.28, 0.61). 
The four ABCC8 tag SNPs were not significantly associated with acute infarct size in non-lacunar strokes. The hyperacute nature of MRI imaging in the MRI dataset (≤48 hours from last seen well, and many within the first 8 hours), may be insufficiently sensitive for assessing CE. Imaging at later time points (>48 hours) or multiple time point comparisons may be required to detect CE associated with SUR1 activity. Future directions may also include assessing the association of ABCC8 tag SNPs with functional outcome.
Authors/Disclosures
Arlinda Deng, MD (University of Virginia Medical Systems)
PRESENTER 		Dr. Deng has nothing to disclose.
No disclosure on file
Anne-Katrin Giese, MD (University Medical Center Hamburg-Eppendorf) Dr. Giese has nothing to disclose.
Markus D. Schirmer, PhD (Massachusetts General Hospital) The institution of Dr. Schirmer has received research support from National Institute of Aging. The institution of Dr. Schirmer has received research support from Heitman Foundation. The institution of Dr. Schirmer has received research support from MIT/MGB.
Kathleen L. Donahue (Massachusetts General Hospital) No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
John Cole, MD (UMD SOM) Dr. Cole has nothing to disclose.
No disclosure on file
Joseph P. Broderick, MD, FAAN (University of Cincinnati) Dr. Broderick has received publishing royalties from a publication relating to health care.
No disclosure on file
No disclosure on file
Robin Lemmens Robin Lemmens has nothing to disclose.
No disclosure on file
James F. Meschia, MD, FAAN (Mayo Clinic) The institution of Dr. Meschia has received research support from NINDS. The institution of Dr. Meschia has received research support from NINDS.
Jonathan Rosand, MD (Massachusetts General Hospital) Dr. Rosand has received personal compensation for serving as an employee of Massachusetts General Hospital. Dr. Rosand has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly and Co. Dr. Rosand has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Rosand has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for National Football League. The institution of Dr. Rosand has received research support from NIH. The institution of Dr. Rosand has received research support from American Heart Association. Dr. Rosand has received personal compensation in the range of $0-$499 for serving as a Peer reviewer with National Institutes of Health. Dr. Rosand has a non-compensated relationship as a Trustee with Columbia University that is relevant to AAN interests or activities.
No disclosure on file
Tatjana Rundek, MD, PhD The institution of Dr. Rundek has received research support from NIH.
Ralph L. Sacco, MD, MS, FAHA Dr. Sacco has received personal compensation in the range of $100,000-$499,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Heart Association. The institution of Dr. Sacco has received research support from NIH, NINDS, NCATS, NIMHD. The institution of Dr. Sacco has received research support from FL Department of Health. Dr. Sacco has received research support from University of Washington, Seattle. Dr. Sacco has received publishing royalties from a publication relating to health care.
Reinhold Schmidt, MD No disclosure on file
Agnieszka Slowik, MD, FAAN (Jagiellonian University) Dr. Slowik has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Boehringer, . Dr. Slowik has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Slowik has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis.
Vincent Thijs, MD Dr. Thijs has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Medtronic. Dr. Thijs has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Allergan. Dr. Thijs has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. Dr. Thijs has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Pfizer. Dr. Thijs has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Boehringer Ingelheim.
Daniel Woo, MD, FAAN (University at Buffalo) The institution of Dr. Woo has received research support from NIH.
Bradford B. Worrall, MD, MSc, FAAN (University Of Virginia Health System) The institution of Dr. Worrall has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. The institution of Dr. Worrall has received research support from NIH.
No disclosure on file
No disclosure on file
Natalia S. Rost, MD, MPH, FAAN, FAHA (Massachusetts General Hospital) Dr. Rost has received personal compensation in the range of $50,000-$99,999 for serving as an officer or member of the Board of Directors for 好色先生. Dr. Rost has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Stroke - AHA/ASA Journal. The institution of Dr. Rost has received research support from NIH. Dr. Rost has received publishing royalties from a publication relating to health care.
Steven J. Kittner, MD, MPH (Dept of Neurology) The institution of Dr. Kittner has received research support from NINDS.