title: Associations between polymorphic variants of the tryptophan hydroxylase 2 gene and obsessive-compulsive disorder.
abstract: OBJECTIVE
  A substantial body of evidence suggests that obsessive-compulsive disorder has a genetic component, and substantial candidate genes for the disorder have been investigated through association analyses. A particular emphasis has been placed on genes related to the serotonergic system, which is likely to play an important role in the pathogenesis of obsessive-compulsive disorder. The gene for tryptophan hydroxylase 2, which is a rate limiting enzyme in serotonin synthesis, is considered an important candidate gene associated with psychiatric disorders.
  
  
  METHODS
  Our sample consisted of 321 subjects (107 diagnosed with obsessive-compulsive disorder and 214 healthy controls), which were genotyped for eight tagSNPs (rs4448731, rs4565946, rs11179000, rs7955501, rs10506645, rs4760820, rs1487275 and rs10879357) covering the entire human tryptophan hydroxylase 2 gene. Statistical analyses were performed using UNPHASED, version 3.0.12, and Haploview®.
  
  
  RESULTS
  Single markers, genotype analysis did not show a significant genetic association with obsessive-compulsive disorder. A significant association between the T-C-T (rs4448731, rs4565946, rs10506645) and C-A-T (rs4565946, rs7955501, rs10506645) haplotypes and obsessive-compulsive disorder was observed, as well as a strong linkage disequilibrium between SNPs rs4448731 and rs4565946, and SNPs rs10506645 and 4760820.
  
  
  CONCLUSIONS
  Our research has not demonstrated the existence of associations between the eight SNPs of TPH2 and obsessive-compulsive disorder. However, two LD and two haplotypes areas were demonstrated, thus suggesting that more studies in TPH2 are needed to investigate the role of tryptophan hydroxylase 2 variants in obsessive-compulsive disorder.
authors.affiliation: Medicine Molecular Program, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. fil_bh@yahoo.com.br
authors.forename: Felipe Filardi da
authors.initials: FF
authors.lastname: Rocha
authors.forename: Nathália Bueno
authors.initials: NB
authors.lastname: Alvarenga
authors.forename: Naira Vassalo
authors.initials: NV
authors.lastname: Lage
authors.forename: Marco Aurélio
authors.initials: MA
authors.lastname: Romano-Silva
authors.forename: Luiz Armando de
authors.initials: LA
authors.lastname: Marco
authors.forename: Humberto
authors.initials: H
authors.lastname: Corrêa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014365:Tryptophan Hydroxylase / Q000235:genetics*; D055815:Young Adult
chemical_list: D014365:Tryptophan Hydroxylase