title: TNF-alpha polymorphisms are associated with obsessive-compulsive disorder.
abstract: BACKGROUND
  Several lines of evidence support an immunologic involvement in obsessive-compulsive disorder (OCD): the increased prevalence of OCD in patients with rheumatic fever (RF), and the aggregation of obsessive-compulsive spectrum disorders among relatives of RF probands. Tumor necrosis factor alpha is a proinflammatory cytokine involved in RF and other autoimmune diseases. Polymorphisms in the promoter region of the TNFA gene have been associated with RF. Given the association between OCD and RF, the goal of the present study was to investigate a possible association between polymorphisms within the promoter region of TNFA and OCD.
  
  
  METHODS
  Two polymorphisms were investigated: -308 G/A and -238 G/A. The allelic and genotypic frequencies of these polymorphisms were examined in 111 patients who fulfilled DSM-IV criteria for OCD and compared with the frequencies in 250 controls.
  
  
  RESULTS
  Significant associations were observed between both polymorphisms and OCD. For -238 G/A, an association between the A allele and OCD was observed (chi(2)=12.05, p=0.0005). A significant association was also observed between the A allele of the -308 G/A polymorphism and OCD (chi(2)=7.09, p=0.007). Finally, a haplotype consisting of genotypes of these two markers was also examined. Significant association was observed for the A-A haplotype (p=0.0099 after correcting for multiple testing).
  
  
  CONCLUSIONS
  There is association between the -308 G/A and -238 G/A TNFA polymorphisms and OCD in our Brazilian sample. However, these results need to be replicated in larger samples collected from different populations.
authors.affiliation: Department of Psychiatry, Institute of Psychiatry, Clinical Hospital, University of São Paulo (USP), Brazil. anah@protoc.com.br
authors.forename: Ana Gabriela
authors.initials: AG
authors.lastname: Hounie
authors.forename: Carolina
authors.initials: C
authors.lastname: Cappi
authors.forename: Quirino
authors.initials: Q
authors.lastname: Cordeiro
authors.forename: Aline Santos
authors.initials: AS
authors.lastname: Sampaio
authors.forename: Ivanil
authors.initials: I
authors.lastname: Moraes
authors.forename: Maria Conceição do
authors.initials: MC
authors.lastname: Rosário
authors.forename: Selma A
authors.initials: SA
authors.lastname: Palácios
authors.forename: Anna Carla
authors.initials: AC
authors.lastname: Goldberg
authors.forename: Homero Pinto
authors.initials: HP
authors.lastname: Vallada
authors.forename: Ariane
authors.initials: A
authors.lastname: Machado-Lima
authors.forename: Eduardo
authors.initials: E
authors.lastname: Nakano
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.forename: David
authors.initials: D
authors.lastname: Pauls
authors.forename: Carlos Alberto B
authors.initials: CA
authors.lastname: Pereira
authors.forename: Luiza
authors.initials: L
authors.lastname: Guilherme
authors.forename: Eurípedes Constantino
authors.initials: EC
authors.lastname: Miguel
mesh_terms: D000328:Adult; D001938:Brazil; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha