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

IF 2 4区医学 Q3 NEUROSCIENCES

Journal of Stroke & Cerebrovascular Diseases Pub Date : 2024-11-01 DOI:10.1016/j.jstrokecerebrovasdis.2024.108109

Arlinda Deng MD , Huichun Xu MD, PhD , Brady J. Gaynor MS , John W. Cole MD, MS , Anne-Katrin Giese MD, PhD , Markus D. Schirmer PhD , Patrick F. McArdle PhD , Braxton D. Mitchell PhD , Ona Wu PhD , Natalia S. Rost MD, MPH , Steven J. Kittner MD, MPH , MRI-GENIE Investigators

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引用次数: 0

Abstract

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.

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SUR1 多态性与急性脑梗塞大小的关系：MRI-GENIE 研究

背景：磺脲类受体 1（SUR1）是大面积缺血性脑卒中脑水肿的已知介质，但基因诱导的反应变异性尚未得到评估。SUR1 由 ABCC8 基因编码，是缺血诱发脑水肿的离子通道调节器。此前对严重创伤性脑损伤的研究表明，ABCC8 基因的四个标记单核苷酸多态性（SNPs）与脑水肿和功能预后有关。我们假设这四个 SNPs 也与非腔隙性缺血性脑卒中的急性梗死面积和功能预后有关：我们利用 2,205 名急性非跛行缺血性脑卒中 MRI-GENetics Interface Exploration (MRI-GENIE) 研究对象，评估了 ABCC8 标记-SNPs 与脑卒中梗死面积（使用弥散加权成像以标准化方式通过 MRI 测量）之间的关系，并对年龄、性别和人群分层进行了调整。MRI-GENIE中的798例脑卒中患者在3个月后可获得改良Rankin量表（mRS）结果，该结果被评估为二分变量（0-2 vs 3-6），并对年龄、性别、脑卒中严重程度（基线NIH脑卒中量表（NIHSS）评分）和人群分层进行了调整：候选 SNP（rs7105832、rs2237982、rs11024286、rs4148622）与 DWI（β= -0.065、-0.057、0.037、0.018；p=0.053、0.078、0.28、0.61）或二分法 mRS 结果（OR=0.80、0.86、1.14、0.结论：ABCC8 基因的 rs7105832、rs2237982、rs11024286、rs4148622 多态性对急性缺血性脑梗死面积或 3 个月功能预后无显著影响。尽管如此，仍有必要使用延迟成像和更敏感的结果测量方法进行进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Stroke & Cerebrovascular Diseases Medicine-Surgery

CiteScore

5.00

自引率

4.00%

发文量

583

审稿时长

62 days

期刊介绍： The Journal of Stroke & Cerebrovascular Diseases publishes original papers on basic and clinical science related to the fields of stroke and cerebrovascular diseases. The Journal also features review articles, controversies, methods and technical notes, selected case reports and other original articles of special nature. Its editorial mission is to focus on prevention and repair of cerebrovascular disease. Clinical papers emphasize medical and surgical aspects of stroke, clinical trials and design, epidemiology, stroke care delivery systems and outcomes, imaging sciences and rehabilitation of stroke. The Journal will be of special interest to specialists involved in caring for patients with cerebrovascular disease, including neurologists, neurosurgeons and cardiologists.