Genetic variation at the BDNF locus: evidence for association with long-term outcome after ischemic stroke

PLoS One. 2014 Dec 3;9(12):e114156. doi: 10.1371/journal.pone.0114156. eCollection 2014.

Abstract

Background and purpose: 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.

Methods: Four 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.

Results: 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; P = 0.006).

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Brain Ischemia / complications
  • Brain-Derived Neurotrophic Factor / genetics*
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Severity of Illness Index
  • Stroke / etiology
  • Stroke / genetics*
  • Stroke / pathology
  • Treatment Outcome
  • Young Adult

Substances

  • Brain-Derived Neurotrophic Factor
  • BDNF protein, human

Grants and funding

This study was supported by the Swedish Research Council (K2011-65X-14605-09-6, K2010-61X-20378-04-3, and 2011-3891), the Swedish state (ALFGBG-148861), the Swedish Heart and Lung Foundation (20100256, 20100244 and 20100228), the Swedish Stroke Association, and the Edit Jacobson, Per-Olof Ahl, Rune and Ulla Amlöv, John and Brit Wennerström, and Tore Nilsson foundations. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.