Abstract T P289: Genetic Variation in the Sulfonylurea Receptor 1 (Sur1)-regulated NCCa-ATP Channel and Stroke Outcome: The Genetics of Early Onset Stroke Study
Background and Purpose: Recent evidence indicates that the sulfonylurea receptor 1 (Sur1)-regulated NCCa-ATP channel is transcriptionally upregulated de novo in cells of the neurovascular unit in response to cerebral ischemia and plays a key role in the development of cerebral edema. We hypothesized that polymorphisms in the genes coding for the proteins associated with this channel may play a role in outcome following ischemic stroke.
Methods: From a biracial population-based study we identified 856 cases of first-ever ischemic stroke in women and men ages 15 to 49 years. 44 SNPs were genotyped in ABCC8, 16 SNPs in TRMP4, and 6 SNPs in SP1. Cases with diabetes were excluded since glyburide is known to block the Sur-1 NCCa-ATP channel. Lacunar strokes were excluded since edema is not hypothesized to contribute to outcome in this stroke subtype. Following exclusions the final population included 235 African-American and 342 Caucasian cases. Utilizing the modified Rankin Score at hospital discharge (0 to 3 and 4/5 combined), ethnicity-stratified regression analyses were performed against genotype in an additive model, controlling for age and gender.
Results: Among Caucasians there were 6 significantly associated TRMP4 SNPs (all with MAF~0.32; p=0.02-0.05) that were in strong linkage disequilibrium (D’>0.80). Among African-Americans there were 3 significantly associated TRMP4 SNPs (p=0.02-0.04). Notably, 2 of these 3 SNPs were also among those identified the Caucasians, rs909010 and rs1175791 (both AA SNPs with MAF~0.45). In ABCC8 there was 1 significant SNP (rs2299640; MAF=0.30; p=0.01) among African-Americans and none among Caucasians. SP1 analyses demonstrated no associated SNPs in either ethnicity.
Conclusions: Genetic variation in TRMP4 may play a role in outcome following ischemic stroke. Confirmatory studies are needed.
Author Disclosures: J.W. Cole: None. K.A. Ryan: None. Y. Cheng: None. D. Koontz: None. C.J. Bean: None. M. Gallagher: None. W.C. Hooper: None. P. McArdle: None. J.R. O’Connell: None. O.C. Stine: None. M.A. Wozniak: None. B.J. Stern: None. B.D. Mitchell: None. S.J. Kittner: None. J.M. Simard: None.
- © 2014 by American Heart Association, Inc.