Deng Arlinda, Xu Huichun, Gaynor Brady J, Cole John W, Giese Anne-Katrin, Schirmer Markus D, McArdle Patrick F, Mitchell Braxton D, Wu Ona, Rost Natalia S, Kittner Steven J
University of Maryland, Baltimore, United States.
Massachusetts General Hospital, Boston, MA, United States.
J Stroke Cerebrovasc Dis. 2025 Jan;34(1):108109. doi: 10.1016/j.jstrokecerebrovasdis.2024.108109. Epub 2024 Nov 1.
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.
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.
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).
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.
磺脲类受体1（SUR1）是已知的大面积缺血性卒中脑水肿的介质，然而，基因诱导的反应变异性尚未得到评估。由ABCC8基因编码的SUR1是缺血性脑水肿中的一种离子通道调节剂。先前对重度创伤性脑损伤的研究表明，ABCC8基因的四个标签单核苷酸多态性（SNP）与脑水肿和功能预后相关。我们假设这四个SNP也与非腔隙性缺血性卒中的急性梗死灶大小和功能预后相关。
我们使用2205名患有急性非腔隙性缺血性卒中的MRI-遗传学接口探索（MRI-GENIE）研究对象，评估4个ABCC8标签SNP与卒中梗死灶大小（使用扩散加权成像从MRI以标准化方式测量）之间的关联，并对年龄、性别和人群分层进行调整。在MRI-GENIE中，798例卒中的一个亚组在3个月时可获得改良Rankin量表（mRS）结局，并将其作为二分变量（0-2 vs. 3-6）进行评估，同时对年龄、性别、卒中严重程度（基线美国国立卫生研究院卒中量表（NIHSS）评分）和人群分层进行调整。
候选SNP，rs7105832、rs2237982、rs11024286、rs4148622，与扩散加权成像（β = -0.065，-0.057，0.037，0.018；p = 0.053，0.078，0.28，0.61）或二分法mRS结局（OR = 0.80，0.86，1.14，0.90；p = 0.117，0.289，0.353，0.502）无统计学关联。
ABCC8基因的rs7105832、rs2237982、rs11024286、rs4148622多态性对急性缺血性梗死灶大小或3个月功能结局未显示出显著影响。尽管如此，仍有必要进行延迟成像和更敏感结局测量的进一步研究。
