Keshavarz Parvaneh, Saberi Alia, Sharafshah Alireza, Asgari Karim, Rezaei Sajjad
a School of Medicine, Cellular and Molecular Research Center , Guilan University of Medical Sciences , Rasht , Iran.
b Department of Neurology , Guilan University of Medical Sciences , Rasht , Iran.
Top Stroke Rehabil. 2016 Aug;23(4):254-60. doi: 10.1080/10749357.2016.1141491. Epub 2016 Feb 17.
Genetic factors like the allele for Brain-Derived Neurotrophic Factor (BDNF) are associated with the outcome of ischemic stroke most likely through affecting neural differentiation and synaptic plasticity. Studies of the association of BDNF G196A gene polymorphism and long-term ischemic stroke outcome in various populations have not been concordant.
In this research, the association of BDNF G196A gene polymorphism and ischemic stroke occurrence were studied in a northern Iranian population with a glance to its 6-month outcome.
The genetic variant of BDNF G196A was examined in Ischemic Stroke (IS) patients (n = 206) and control group (n = 200). In IS individuals, outcome variables such as stroke severity, functional disability, and cognitive impairment were examined, respectively, by NIHSS, Barthel Index, and MoCA in an average of 202 days after the stroke occurrence.
The frequency of risk allele G was 12.1% in IS patients and 5.5% in healthy individuals; and the difference was statistically significant (p < 0.0001). The frequency of risk genotype GG, heterozygote and homozygote were 0% and 1%, 24%.3% and 9%, 75.7% and 90%, respectively, for IS and control groups (p < 0.05). After controlling the phenotype confounding factors, logistic regression analysis showed that there was a borderline significant relationship between genotype BDNF GA + GG and IS occurrence (AOR = 1.997,95% CI: 0.252-1.010, p = 0.051). There was no significant difference between the various genotypic groups regarding the severity of the stroke and functional disability. Yet, G allele carriers had more cognitive impairment after IS (p = 0.002).
For the first time in an Iranian population, it was demonstrated that BDNF G196A variant plays a major role in stroke occurrence and consequences. It is suggested that, after IS, G allele carriers should have precedence for medicinal and rehabilitation interventions, in order to reduce their cognitive deficiency.
脑源性神经营养因子(BDNF)等位基因等遗传因素最有可能通过影响神经分化和突触可塑性与缺血性中风的预后相关。不同人群中BDNF G196A基因多态性与缺血性中风长期预后的关联研究结果并不一致。
本研究在伊朗北部人群中研究BDNF G196A基因多态性与缺血性中风发生的关联,并观察其6个月的预后情况。
对206例缺血性中风(IS)患者和200例对照组进行BDNF G196A基因变异检测。在IS患者中,分别在中风发生后平均202天,通过美国国立卫生研究院卒中量表(NIHSS)、巴氏指数和蒙特利尔认知评估量表(MoCA)对中风严重程度、功能残疾和认知障碍等预后变量进行检测。
IS患者中风险等位基因G的频率为12.1%,健康个体中为5.5%;差异具有统计学意义(p<0.0001)。IS组和对照组中风险基因型GG、杂合子和纯合子的频率分别为0%和1%、24.3%和9%、75.7%和90%(p<0.05)。在控制表型混杂因素后,逻辑回归分析显示基因型BDNF GA+GG与IS发生之间存在临界显著关系(比值比[AOR]=1.997,95%置信区间[CI]:0.252-1.010,p=0.051)。不同基因型组在中风严重程度和功能残疾方面无显著差异。然而,G等位基因携带者在IS后有更多的认知障碍(p=0.002)。
在伊朗人群中首次证明,BDNF G196A变异在中风发生及后果中起主要作用。建议在IS后,G等位基因携带者应优先接受药物和康复干预,以减少其认知缺陷。