TNF-alpha polymorphisms are associated with obsessive-compulsive disorder.
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.
Hounie
Ana Gabriela
AG
Department of Psychiatry, Institute of Psychiatry, Clinical Hospital, University of São Paulo (USP), Brazil. anah@protoc.com.br
Cappi
Carolina
C
Cordeiro
Quirino
Q
Sampaio
Aline Santos
AS
Moraes
Ivanil
I
Rosário
Maria Conceição do
MC
Palácios
Selma A
SA
Goldberg
Anna Carla
AC
Vallada
Homero Pinto
HP
Machado-Lima
Ariane
A
Nakano
Eduardo
E
Kalil
Jorge
J
Pauls
David
D
Pereira
Carlos Alberto B
CA
Guilherme
Luiza
L
Miguel
Eurípedes Constantino
EC
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*
D014409:Tumor Necrosis Factor-alpha