<i>BDNF</i> genotype percentages by stroke outcome status as measured by the modified Rankin Scale (mRS) at 3 months, 2 years and 7 years post stroke.

<p><i>BDNF</i> genotype percentages by stroke outcome status as measured by the modified Rankin Scale (mRS) at 3 months, 2 years and 7 years post stroke.</p

Odds ratios and 95% confidence intervals for the associations between SNPs in <i>BDNF</i> and poor functional outcome after stroke as measured by mRS ≧2 at 3 months (A), 2 years (B), and 7 years (C) post-stroke.

<p>White boxes, adjusted for age and sex; grey boxes adjusted for age, sex, smoking, diabetes, hypertension, hyperlipidemia, TOAST subtype and NIHSS during the acute phase. † <i>P</i><0.01 compared with good outcome after stroke. Patients that died after the 2-year follow-up were excluded from the 7-year analyses (n = 73).</p

<i>BDNF</i> genotype frequency distribution and association to recovery as measured by the change in NIHSS score from acute stroke to 3 months post-stroke (ΔNIHSS).

<p><i>BDNF</i> genotype frequency distribution and association to recovery as measured by the change in NIHSS score from acute stroke to 3 months post-stroke (ΔNIHSS).</p

<i>BDNF</i> genotype frequency distribution and association with stroke severity during the acute phase, as measured by the NIHSS.

<p><i>BDNF</i> genotype frequency distribution and association with stroke severity during the acute phase, as measured by the NIHSS.</p

Genetic Variation at the <i>BDNF</i> Locus: Evidence for Association with Long-Term Outcome after Ischemic Stroke

<div><p>Background and Purpose</p><p>Rates 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.</p><p>Methods</p><p>Four <i>BDNF</i> 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.</p><p>Results</p><p>No 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; <i>P</i> =  0.006).</p><p>Conclusions</p><p>BDNF 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.</p></div

Baseline characteristics of the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS).

<p>Baseline characteristics of the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS).</p

Features of TOAST classification of ischemic stroke subtypes.

<p>Adapted from Adams and colleagues <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072133#pone.0072133-Adams1" target="_blank">[28]</a>.</p><p>LVD – large vessel disease; SVD – small vessel disease; CE- cardioembolic.</p

Correlations between plasma levels of C3 and C3a, hsCRP, and SSS.

<p>Values represent Spearman’s correlation coefficients (ρ) with significance levels denoted as follows:</p>*<p><i>P<</i>0.05;</p>**<p><i>P</i><0.01;</p>***<p><i>P</i><0.001.</p>§<p>variable measured at the same time point as the respective indicated measurements of C3 or C3a.</p><p>–indicates non-relevant correlation.</p><p>hsCRP – high sensitivity C-reactive protein; SSS – Scandinavian Stroke Scale score; CE- cardioembolic; SVD – small vessel disease.</p

Demographic and clinical characteristics of the study population.

<p>Differences between cases and controls were examined with χ² test for proportions or Mann-Whitney U or Wilcoxon signed ranked test for continuous variables.</p>*<p>P<0.05;</p>**<p>P<0.01;</p>***<p>P<0.001 for comparisons against controls;</p>#<p>P<0.05;</p>###<p>P<0.001 for comparisons against CE subtype;</p>&&&<p>P<0.001 for comparisons against the acute phase. CE- cardioembolic; SVD - small vessel disease; IQ-R – inter-quartile range; BMI – body mass index; SSS – Scandinavian Stroke Scale score; hsCRP – high sensitivity C-reactive protein.</p

Univariate and multivariate ORs with 95% CIs of association between C3 and C3a levels and stroke.

<p>OR – odds ratio; CI – confidence intervals; SVD – small vessel disease, CE – cardioembolic.</p><p>Model 1: adjusted for age, sex, hypertension, smoking, diabetes and hyperlipidemia;</p>*<p><i>P<</i>0.05;</p>**<p><i>P</i><0.01;</p>***<p><i>P</i><0.001.</p