Zhao Hongqin, Cao Yanyan, Chen Honghua, Xu Wanqun, Sun Ximei, Pan Xudong
Department of Neurology, the Affiliated Hospital of Qingdao University, Qingdao 266000, China.
Department of Neurology, Qingdao University, Qingdao 266000, China.
Gene. 2017 May 20;613:25-29. doi: 10.1016/j.gene.2017.02.029. Epub 2017 Mar 10.
Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily and is involved in the progress of atherosclerosis. We chose a gene polymorphism locus, OPG rs3102735, to explore how OPG gene polymorphisms relate to the occurrence of ischemic stroke and microembolic signals and to evaluate their relationship with the severity of neurologic deficits at admission and the degree of vascular stenosis.
We studied 251 patients diagnosed with large artery atherosclerosis (LAA) stroke and 121 controls. The LAA stroke patients were divided into clinical subgroups according to the presence of microembolic signals, severity of neurologic deficits at admission, and the degree of vascular stenosis. The OPG rs3102735 gene polymorphism was examined by polymerase chain reaction and restriction fragment length polymorphism. The microembolic signals (MES) were monitored by transcranial Doppler (TCD) for 60min within 72h of stroke onset. The severity of neurologic deficits at admission was evaluated by the National Institutes of Health Stroke Scale (NIHSS).
The CC+CT genotypes and allele C frequencies of the rs3102735 gene polymorphism were significantly higher in the LAA group than in the control group (39% vs. 25.6%, P=0.026; 21.7% vs.13.2%, P=0.006), higher in MES-positive compared to MES-negative patients (58.7% vs. 32.4%, P<0.01; 34.1% vs.17.6%, P<0.01), and higher in patients with an NIHSS Score (≥6) than in those with an NIHSS Score (<6) (46.9% vs.33.3%, P=0.031; 43.4% vs.18.3%, P=0.04). However, the genotypes and allele frequencies of SNPs in rs3102735 did not show significant differences in the degree of vascular stenosis (P>0.05).
Our findings suggest that the OPG rs3102735 gene polymorphism might be related to the occurrence of LAA ischemic stroke, microembolic signals and stroke severity and not the degree of vascular stenosis.
骨保护素（OPG）是肿瘤坏死因子受体超家族的成员，参与动脉粥样硬化的进展。我们选择了一个基因多态性位点OPG rs3102735，以探讨OPG基因多态性与缺血性脑卒中及微栓子信号发生的关系，并评估其与入院时神经功能缺损严重程度及血管狭窄程度的关系。
我们研究了251例诊断为大动脉粥样硬化（LAA）性脑卒中的患者和121例对照者。LAA性脑卒中患者根据微栓子信号的存在、入院时神经功能缺损的严重程度及血管狭窄程度分为临床亚组。采用聚合酶链反应和限制性片段长度多态性检测OPG rs3102735基因多态性。在脑卒中发病72小时内，采用经颅多普勒（TCD）监测微栓子信号（MES）60分钟。采用美国国立卫生研究院卒中量表（NIHSS）评估入院时神经功能缺损的严重程度。
rs3102735基因多态性的CC + CT基因型和等位基因C频率在LAA组显著高于对照组（39% 对25.6%，P = 0.026；21.7% 对13.2%，P = 0.006），MES阳性患者高于MES阴性患者（58.7% 对32.4%，P < 0.01；34.1% 对17.6%，P < 0.01），NIHSS评分（≥6）的患者高于NIHSS评分（<6）的患者（46.9% 对33.3%，P = 0.031；43.4% 对18.3%，P = 0.04）。然而，rs3102735中SNP的基因型和等位基因频率在血管狭窄程度方面未显示出显著差异（P > 0.05）。
我们的研究结果表明，OPG rs3102735基因多态性可能与LAA缺血性脑卒中的发生、微栓子信号及脑卒中严重程度有关，而与血管狭窄程度无关。
