title: Brain-derived neurotrophic factor gene Val66Met polymorphism modulates reversible cerebral vasoconstriction syndromes.
abstract: BACKGROUND
  Reversible cerebral vasoconstriction syndrome (RCVS) could be complicated by cerebral ischemic events. Hypothetical mechanisms of RCVS involve endothelial dysfunction and sympathetic overactivity, both of which were reported to be related to brain-derived neurotrophic factor (BDNF). The study investigated the association between functional BDNF Val66Met polymorphism and RCVS.
  
  
  METHODS
  Patients with RCVS and controls were prospectively recruited and genotyped for the BDNF Val66Met polymorphism. Magnetic resonance angiography (MRA) and transcranial color-coded Doppler sonography were employed to evaluate cerebral vasoconstriction. Genotyping results, clinical parameters, vasoconstriction scores, mean flow velocities of the middle cerebral artery (V(MCA)), and Lindegaard indices were analyzed. Split-sample approach was employed to internally validate the data.
  
  
  RESULTS
  Ninety Taiwanese patients with RCVS and 180 age- and gender-matched normal controls of the same ethnicity completed the study. The genotype frequencies did not differ between patients and controls. Compared to patients with Met/Met homozygosity, patients with Val allele had higher mean vasoconstriction scores of all arterial segments (1.60±0.72 vs. 0.87±0.39, p<0.001), V(MCA) values (116.7±36.2 vs. 82.7±17.9 cm/s, p<0.001), and LI (2.41±0.91 vs. 1.89±0.41, p = 0.001). None of the Met/Met homozygotes, but 38.9% of the Val carriers, had V(MCA) values of >120 cm/s (p<0.001). Split-sample validation by randomization, age, entry time or residence of patients demonstrated concordant findings.
  
  
  CONCLUSIONS
  Our findings link BDNF Val66Met polymorphism with the severity of RCVS for the first time and implicate possible pathogenic mechanisms for vasoconstriction in RCVS.
authors: Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
authors: Shih-Pin
authors: SP
authors: Chen
authors: Jong-Ling
authors: JL
authors: Fuh
authors: Shuu-Jiun
authors: SJ
authors: Wang
authors: Shih-Jen
authors: SJ
authors: Tsai
authors: Chen-Jee
authors: CJ
authors: Hong
authors: Albert C
authors: AC
authors: Yang
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D001921:Brain / Q000098:blood supply* / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003251:Constriction, Pathologic; D003710:Demography; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results; D013577:Syndrome; D014661:Vasoconstriction / Q000235:genetics*
chemical_list: D019208:Brain-Derived Neurotrophic Factor