The association of SUR1 polymorphisms with acute infarct size: The MRI-GENIE study

Background

The sulfonylurea receptor 1 (SUR1) is a known mediator of cerebral edema in large ischemic strokes, however, genetically induced response variability has yet to be evaluated. SUR1, encoded by the ABCC8 gene, is an ion channel regulator in ischemia-induced cerebral edema. Previous studies in severe traumatic brain injury demonstrated four tag single nucleotide polymorphisms (SNPs) of the ABCC8 gene to be associated with cerebral edema and functional outcome. We hypothesized that these four SNPs would also be associated with acute infarct size and functional outcome in non-lacunar ischemic stroke.

Methods

Using 2,205 MRI–GENetics Interface Exploration (MRI-GENIE) study subjects with acute non-lacunar ischemic strokes, we evaluated the association between the 4 ABCC8 tag-SNPs and stroke infarct size (as measured in a standardized fashion from MRIs using diffusion-weighted imaging), adjusting for age, sex and population stratification. Modified Rankin scale (mRS) outcome was available at 3-months for a subset of 798 strokes in MRI-GENIE and was evaluated as a dichotomous variable (0-2 vs. 3-6), adjusting for age, sex, stroke severity (baseline NIH Stroke Scale (NIHSS) score), and population stratification.

Results

The candidate SNPs, rs7105832, rs2237982, rs11024286, rs4148622, were not statistically associated with DWI (beta = −0.065, −0.057, 0.037, 0.018; p = 0.053, 0.078, 0.28, 0.61) or dichotomous mRS outcome (OR = 0.80, 0.86, 1.14, 0.90; p = 0.117, 0.289, 0.353, 0.502).

Conclusion

rs7105832, rs2237982, rs11024286, rs4148622 polymorphisms of the ABCC8 gene did not demonstrate a significant effect on acute ischemic infarct size or 3-month functional outcome. Nonetheless, further studies with delayed imaging and more sensitive outcome measures remain warranted.