Abstract
Objectives The collateral circulation near the cerebral artery occlusion can contribute to the relief of the symptoms and signs of stroke. Genetic factors play a decisive role in the difference in collateral circulation. Survivin, encoded by the baculoviral inhibitor of apoptosis (IAP) repeat-containing 5 gene (BIRC5), plays an important role in maintaining long-term endothelial integrity and homeostasis and as an angiogenic factor in the treatment of vascular diseases. We hypothesized that genetic variations in the BIRC5 gene may contribute to severity by influencing the collateral circulation. This study aimed at examining how the polymorphism of the BIRC5 gene correlated with the collateral circulation and severity of large artery atherosclerotic stroke. Methods This study enrolled 428 patients with large artery atherosclerotic stroke. There are no statistical differences in age, sex, social behavior, such as smoking and drinking, between the groups classified by the collateral circulation and by the severity of stroke (P > 0.01). Direct sequencing was performed for the genotyping of single nucleotide polymorphism (SNP) of BIRC5 (rs2071214). The enrolled patients were divided into several subgroups based on the collateral flow grading system from the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR), the results of the National Institutes of Health Stroke Survey (NIHSS) (6 as a threshold), and the score of the modified Rankin scale (mRS) (for the prediction of prognosis, 2 as a threshold). Differences among subgroups were identified through logistic regression. Results The analysis of collateral circulation revealed the significant correlation of SNP of rs2071214 with the development of poor collateral circulation of large artery atherosclerotic stroke in the additive model (GG vs. AA, odds ratio (OR) = 3.592, 95% confidence interval (CI) = 1.410–9.150, and P=0.007) and the recessive model (GG vs. AA/GA, OR = 3.313, 95% CI = 1.420–7.727, and P=0.006). The analysis of stroke severity exposed the significant role of the SNP of rs2071214 in increasing stroke severity in the dominant model (GA/GG vs. AA, OR = 1.658, 95% CI = 1.017–2.703, and P=0.043) and the additive model (GA vs. AA, OR = 1.717, 95% CI = 1.021–2.888, and P=0.042). However, the analysis of the short-term outcome indicated that three genetic models were not associated with short-term outcomes in the additive model (GA vs. AA, P=0.815, GG vs. AA, and P=0.336), the dominant model (GA/GG vs. AA and P=0.589), and the recessive model (GG vs. AA/GA and P=0.342). Conclusion Our findings identified the SNP of rs2071214 of the BIRC5 gene as a risk factor for the poor compensatory ability of collateral circulation and a predictor of stroke severity in large artery atherosclerotic stroke, which suggested that the SNP of rs2071214 can serve as an innovative therapeutic target for patients with acute ischemic stroke.
Highlights
Stroke has caused the most deaths in China and contributed a lot to adult disability in recent years [1]
Within 7 days of onset, the whole of cerebral vessels was detected by digital subtraction angiography (DSA), and the endovascular procedure was performed by experienced interventional neurologists
Two experienced neurologists judged the results of the angiography with disagreements resolved by a third neurologist. e WarfarinAspirin Symptomatic Intracranial Disease (WASID) method was applied to the estimation of the intracranial arterial stenosis level [18]. e North American Symptomatic Carotid Endarterectomy Trial (NASCET) standard was applied to the estimation of the extracranial arterial stenosis level [19]. e stenosis degree ≥70% indicated severe stenosis or occlusion
Summary
Stroke has caused the most deaths in China and contributed a lot to adult disability in recent years [1]. Survivin, encoded by the BIRC5 gene, has the lowest molecular weight in the IAP protein family [9] It is involved in protecting the cells by inhibiting apoptosis, regulating cell mitosis, and adapting cells to an unfavorable environment [10]. As found from a mouse model, the BIRC5 gene-transfected cells presented significant increases in the expression of cell cycle proteins, mRNA and protein expressions of survivin, cell proliferation, and invasiveness and migration activities [11]. E close correlation of collateral circulation with the susceptibility and severity of an ischemic stroke is worth exploring in terms of its clinical significance. The potential association of the allelic variation of BIRC5 rs2071214 with the collateral circulation and severity of patients with ischemic stroke was explored deeply to examine the possible mechanism
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