title: The Met allele of BDNF Val66Met polymorphism is associated with increased BDNF levels in generalized anxiety disorder.
abstract: BACKGROUND
  Generalized anxiety disorder (GAD) is a common psychiatric disorder characterized by long-term worry, tension, nervousness, fidgeting, and symptoms of autonomic system hyperactivity. The neurobiology of this disorder is still unclear, although it has been shown consistently that the environment and the genetic profile could increase its risk. We examined whether a polymorphism in the brain-derived neurotrophic factor (BDNF) gene, which plays a role in neuroplasticity and memory, could increase the vulnerability to this disorder.
  
  
  METHODS
  In our study, 816 participants from a population-based study were genotyped by qPCR for the BDNF functional variant rs6265 (Val66Met) and the BDNF serum levels were measured by ELISA.
  
  
  RESULTS
  Our results showed a significant association between the Met allele and risk for GAD (P=0.014), but no differences were observed in the serum levels of BDNF according to diagnosis (P=0.531) or genotype distribution (P=0.197). However, after stratification according to the GAD diagnosis, the Met allele was associated significantly with an increase in serum BDNF levels compared with the Val/Val genotype in GAD participants (F=3.93; P=0.048). The logistic regression analysis confirmed the independent association of Met allele as a risk factor for development of GAD after adjusting for confounder variables (β=0.528; 95% confidence interval: 0.320-0.871; P=0.012).
  
  
  CONCLUSIONS
  These results suggest that BDNF could be involved in the neurobiology of GAD and might represent a useful marker associated with the disease.
authors.affiliation: aPost Graduation in Health and Behavior, Catholic University of Pelotas, Pelotas, RS bCellular and Molecular Biology, Pontifical Catholic University of Rio Grande do Sul cEndocrinology Service dDepartment of Biochemistry, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Fernanda P
authors.initials: FP
authors.lastname: Moreira
authors.forename: Júlia D
authors.initials: JD
authors.lastname: Fabião
authors.forename: Guilherme
authors.initials: G
authors.lastname: Bittencourt
authors.forename: Carolina D
authors.initials: CD
authors.lastname: Wiener
authors.forename: Karen
authors.initials: K
authors.lastname: Jansen
authors.forename: Jean P
authors.initials: JP
authors.lastname: Oses
authors.forename: Luciana de Ávila
authors.initials: Lde Á
authors.lastname: Quevedo
authors.forename: Luciano D M
authors.initials: LD
authors.lastname: Souza
authors.forename: Daisy
authors.initials: D
authors.lastname: Crispim
authors.forename: Luiz V
authors.initials: LV
authors.lastname: Portela
authors.forename: Ricardo T
authors.initials: RT
authors.lastname: Pinheiro
authors.forename: Diogo R
authors.initials: DR
authors.lastname: Lara
authors.forename: Manuella P
authors.initials: MP
authors.lastname: Kaster
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: da Silva
authors.forename: Gabriele
authors.initials: G
authors.lastname: Ghisleni
mesh_terms: D000328:Adult; D000483:Alleles; D001008:Anxiety Disorders / Q000097:blood* / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood* / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014633:Valine / Q000235:genetics; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human; D008715:Methionine; D014633:Valine