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端粒长度与缺血性脑卒中风险和表型的关联。

The association between telomere length and ischemic stroke risk and phenotype.

机构信息

Department of Neurology, Faculty of Medicine, Hacettepe University, Sihhiye, 06100, Ankara, Turkey.

Department of Medical Genetics, Faculty of Medicine, Ankara University, Ankara, Turkey.

出版信息

Sci Rep. 2021 May 26;11(1):10967. doi: 10.1038/s41598-021-90435-9.

Abstract

The chronological age of a person is a key determinant of etiology and prognosis in the setting of ischemic stroke. Telomere length, an indicator of biological aging, progressively shortens with every cell cycle. Herein, we determined telomere length from peripheral blood leukocytes by Southern blot analyses in a prospective cohort of ischemic stroke patients (n = 163) and equal number of non-stroke controls and evaluated its association with various ischemic stroke features including etiology, severity, and outcome. A shorter telomere length (i.e. lowest quartile; ≤ 5.5 kb) was significantly associated with ischemic stroke (OR 2.95, 95% CI 1.70-5.13). This significant relationship persisted for all stroke etiologies, except for other rare causes of stroke. No significant association was present between admission lesion volume and telomere length; however, patients with shorter telomeres had higher admission National Institutes of Health Stroke Scale scores when adjusted for chronological age, risk factors, etiology, and infarct volume (p = 0.046). On the other hand, chronological age, but not telomere length, was associated with unfavorable outcome (modified Rankin scale > 2) and mortality at 90 days follow-up. The association between shorter telomere length and more severe clinical phenotype at the time of admission, might reflect reduced resilience of cerebral tissue to ischemia as part of biological aging.

摘要

一个人的实际年龄是缺血性脑卒中发病机制和预后的关键决定因素。端粒长度是生物老化的一个指标,它会随着每个细胞周期的进行而逐渐缩短。在此,我们通过对缺血性脑卒中患者(n=163)和数量相等的非脑卒中对照者的外周血白细胞进行Southern blot 分析,确定了端粒长度,并评估了其与各种缺血性脑卒中特征(包括病因、严重程度和结局)的相关性。端粒长度较短(即最低四分位数;≤5.5kb)与缺血性脑卒中显著相关(OR 2.95,95%CI 1.70-5.13)。这种显著的关系存在于除其他罕见的脑卒中病因以外的所有脑卒中病因中。入院时的病灶体积与端粒长度之间没有显著的相关性;然而,在校正实际年龄、危险因素、病因和梗死体积后,端粒较短的患者入院时的美国国立卫生研究院卒中量表评分更高(p=0.046)。另一方面,实际年龄与不良结局(改良 Rankin 量表评分>2)和 90 天随访时的死亡率相关,而不是端粒长度。端粒较短与入院时更严重的临床表型之间的关联,可能反映了脑组织对缺血的弹性降低,这是生物老化的一部分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7be/8155040/ba7e9f2b240a/41598_2021_90435_Fig1_HTML.jpg

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