Association between the dopamine receptor D4 (DRD4) gene and obsessive-compulsive disorder.
Obsessive-compulsive disorder (OCD) is a frequent and disabling anxiety disorder. Dopamine (DA) might be involved in its pathophysiology, therefore DA receptors are candidate genes in OCD. A 48-base pairs (bp) polymorphism located in the third exon of the dopamine receptor type 4 (DRD4) gene has been described. Previous case control studies, however, have reported inconclusive results in OCD. The aim of the study was to study this polymorphism in a family-based association study of 55 trios. Extended transmission-disequilibrium test (ETDT) for preferential allele transmission in this group showed an absence of transmission of the allele 2 for the 48 bp repeat polymorphism of the DRD4 gene (P = 0.005). Moreover, in a population-based association study, we found a significantly lower frequency of the allele 2 in patients suffering from OCD compared to ethnically-matched controls (P = 0.02). We found no association of DRD4 48 bp polymorphism with OCD in the subgroup of patients with comorbid tics. This study is the first to report on a significant association of variants of the DRD4 gene in OCD, found on both family- and population-based studies. The results suggest that the 2 allele or a nearby genetic variation could have a protective effect against OCD symptoms.
Millet
Bruno
B
INSERM E0117 Paris V, University Department of Psychiatry, Sainte-Anne Hospital, Paris, France. millet@chsa.broca.inserm.fr
Chabane
Nadia
N
Delorme
Richard
R
Leboyer
Marion
M
Leroy
Sophie
S
Poirier
Marie-France
MF
Bourdel
Marie-Chantal
MC
Mouren-Simeoni
Marie-Christine
MC
Rouillon
Fréderic
F
Loo
Henri
H
Krebs
Marie-Odile
MO
D000293:Adolescent; D000328:Adult; D000483:Alleles; D004247:DNA / Q000235:genetics; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050638:Receptors, Dopamine D4
C493599:DRD4 protein, human; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D004247:DNA