title: The role of brain-derived neurotrophic factor (BDNF) Val66Met genetic polymorphism in bipolar disorder: a case-control study, comorbidities, and meta-analysis of 16,786 subjects.
abstract: OBJECTIVE
  The aim of this study was to evaluate the association of Val66Met brain-derived neurotrophic factor (BDNF) polymorphism with bipolar disorder in (i) a meta-analysis and (ii) a case-control study in a Mexican population. We also investigated the possible association of this polymorphism with clinical features.
  
  
  METHODS
  We performed a keyword search of the PubMed and Web of Science databases. A total of 22 studies that have investigated the association of Val66Met (rs6265) with bipolar disorder were selected for inclusion and combined with random effects meta-analysis, using allelic, additive, dominant, and recessive models. Finally, the single nucleotide polymorphism (rs6265) Val66Met in the BDNF gene was genotyped and compared between 139 patients with bipolar disorder and 141 healthy volunteers in a Mexican population.
  
  
  RESULTS
  The pooled results from the meta-analysis (9,349 cases and 7,437 controls) did not show a significant association in any of the models. The same results were obtained in our case-control study when analyzing the distribution of the genotypic frequencies of the Val66Met polymorphism in patients with bipolar disorder. However, when we analyzed the association between rs6265 and lifetime history of suicidal behavior, we found an association between genotype Val-Val and suicide attempt (p = 0.02).
  
  
  CONCLUSIONS
  Although the present study has some limitations, the results indicate a lack of association between the Val66Met polymorphism and bipolar disorder. However, in our case-control study in a Mexican population, the Val66Met polymorphism was associated with suicidal behavior in patients with bipolar disorder. Nevertheless, it is important to consider potential interactions of the BDNF gene, the environment, and different inheritance patterns, when carrying out future genetic studies with larger samples.
authors.affiliation: División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, Villahermosa, Tabasco.
authors.forename: Thelma Beatriz
authors.initials: TB
authors.lastname: González-Castro
authors.forename: Humberto
authors.initials: H
authors.lastname: Nicolini
authors.forename: Nuria
authors.initials: N
authors.lastname: Lanzagorta
authors.forename: Lilia
authors.initials: L
authors.lastname: López-Narváez
authors.forename: Alma
authors.initials: A
authors.lastname: Genis
authors.forename: Sherezada
authors.initials: S
authors.lastname: Pool García
authors.forename: Carlos Alfonso
authors.initials: CA
authors.lastname: Tovilla-Zárate
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D016022:Case-Control Studies; D004151:Dipeptides / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013405:Suicide / Q000523:psychology* / Q000706:statistics & numerical data
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004151:Dipeptides; C034792:valylvaline; C579455:BDNF protein, human
keywords: Mexican population; bipolar disorder; brain-derived neurotrophic factor (BDNF) gene; meta-analysis