title: Associations of BDNF genotype and promoter methylation with acute and long-term stroke outcomes in an East Asian cohort.
abstract: BACKGROUND
  Brain derived neurotrophic factor (BDNF) has been shown to play an important role in poststroke recovery. BDNF secretion is influenced by genetic and epigenetic profiles. This study aimed to investigate whether BDNF val66met polymorphism and promoter methylation status were associated with outcomes at two weeks and one year after stroke.
  
  
  RESULTS
  A total of 286 patients were evaluated at the time of admission and two weeks after stroke, and 222 (78%) were followed one year later in order to evaluate consequences of stroke at both acute and chronic stages. Stroke outcomes were dichotomised into good and poor by the modified Rankin Scale. Stroke severity (National Institutes of Health Stroke Scale), physical disability (Barthel Index), and cognitive function (Mini-Mental State Examination) were measured. Associations of BDNF genotype and methylation status on stroke outcomes and assessment scale scores were investigated using logistic regression, repeated measures ANOVA and partial correlation tests. BDNF val66met polymorphism was independently associated with poor outcome at 2 weeks and at 1 year, and with worsening physical disability and cognitive function over that period. Higher BDNF promoter methylation status was independently associated with worse outcomes at 1 year, and with the worsening of physical disability and cognitive function. No significant genotype-methylation interactions were found.
  
  
  CONCLUSIONS
  A role for BDNF in poststroke recovery was supported, and clinical utility of BDNF genetic and epigenetic profile as prognostic biomarkers and a target for drug development was suggested.
authors.affiliation: Department of Psychiatry, Chonnam National University Medical School, Gwangju, Korea. jmkim@chonnam.ac.kr
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Robert
authors.initials: R
authors.lastname: Stewart
authors.forename: Man-Seok
authors.initials: MS
authors.lastname: Park
authors.forename: Hee-Ju
authors.initials: HJ
authors.lastname: Kang
authors.forename: Sung-Wan
authors.initials: SW
authors.lastname: Kim
authors.forename: Il-Seon
authors.initials: IS
authors.lastname: Shin
authors.forename: Hye-Ran
authors.initials: HR
authors.lastname: Kim
authors.forename: Myung-Geun
authors.initials: MG
authors.lastname: Shin
authors.forename: Ki-Hyun
authors.initials: KH
authors.lastname: Cho
authors.forename: Jin-Sang
authors.initials: JS
authors.lastname: Yoon
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012720:Severity of Illness Index; D020521:Stroke / Q000235:genetics / Q000503:physiopathology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human