Abstract
Background and PurposeRates and extent of recovery after stroke vary considerably between individuals and genetic factors are thought to contribute to post-stroke outcome. Brain-derived neurotrophic factor (BDNF) plays important roles in brain plasticity and repair and has been shown to be involved in stroke severity, recovery, and outcome in animal models. Few clinical studies on BDNF genotypes in relation to ischemic stroke have been performed. The aims of the present study are therefore to investigate whether genetic variation at the BDNF locus is associated with initial stroke severity, recovery and/or short-term and long-term functional outcome after ischemic stroke.MethodsFour BDNF tagSNPs were analyzed in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS; 600 patients and 600 controls, all aged 18–70 years). Stroke severity was assessed using the NIH Stroke Scale (NIHSS). Stroke recovery was defined as the change in NIHSS over a 3-month period. Short- and long-term functional outcome post-stroke was assessed using the modified Rankin Scale at 3 months and at 2 and 7 years after stroke, respectively.ResultsNo SNP was associated with stroke severity or recovery at 3 months and no SNP had an impact on short-term outcome. However, rs11030119 was independently associated with poor functional outcome 7-years after stroke (OR 0.66, 95% CI 0.46–0.92; P = 0.006).ConclusionsBDNF gene variants were not major contributors to ischemic stroke severity, recovery, or short-term functional outcome. However, this study suggests that variants in the BDNF gene may contribute to poor long-term functional outcome after ischemic stroke.
Highlights
Is stroke the second leading cause of death in developed countries, but it is the leading cause of disability in adults [1]
The upper age limit of 70 years was chosen based on studies showing that the influences of genetic factors are more pronounced in younger individuals [23]
The traditional vascular risk factors hypertension, diabetes, hyperlipidemia and smoking were all over-represented in overall ischemic stroke and the four main etiologic subtypes as compared to controls
Summary
Is stroke the second leading cause of death in developed countries, but it is the leading cause of disability in adults [1]. The most well studied genetic variant at the BDNF locus comprises the common Val66Met polymorphism (rs6265), which affects intracellular BDNF trafficking and activity-dependent secretion of BDNF in neurons [8, 9] In human subjects, this polymorphism has been associated with cortical and hippocampal-dependent plasticity, some forms of learning and memory performance, as well as changes in brain morphology [9,10,11,12]. Brain-derived neurotrophic factor (BDNF) plays important roles in brain plasticity and repair and has been shown to be involved in stroke severity, recovery, and outcome in animal models. The aims of the present study are to investigate whether genetic variation at the BDNF locus is associated with initial stroke severity, recovery and/or short-term and longterm functional outcome after ischemic stroke. This study suggests that variants in the BDNF gene may contribute to poor long-term functional outcome after ischemic stroke
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