DRD4 gene and obsessive compulsive disorder: do symptom dimensions have specific genetic correlates?

The dopamine D4 receptor (DRD4) is a promising candidate gene in obsessive compulsive disorder (OCD). A 48-bp variable number of tandem repeats (VNTR) sequence in exon 3 has been studied previously, and alleles containing 2-11 repeats (2R-11R) have been identified. We investigated the association of DRD4 VNTR polymorphism with OCD and its relationship with various clinical parameters (age of onset, gender, family history, co-morbidity, factor-analyzed symptom dimensions and insight). One hundred and seventy three South Indian OCD patients (DSM-IV) recruited from a specialty OCD clinic were evaluated using the Yale-Brown obsessive compulsive scale (YBOCS), YBOCS item-11 for insight, Mini International Neuropsychiatric Interview (MINI) plus, tic disorder subsection of the MINI-KID and Clinical Global Impression scale. 201 healthy controls were evaluated using MINI plus. All subjects were genotyped for the DRD4 VNTR polymorphism. Genotype frequencies did not deviate significantly from the Hardy-Weinberg equilibrium. Case-control association analysis revealed that the 7R allele frequency was significantly greater in OCD patients than controls. This difference was restricted to the women subsample when performing the gender sub-analysis. Among other clinical variables examined, factor 3 (symmetry) was associated with presence of 2R allele. Linear regression analysis confirmed the association of symmetry dimension with the 2R allele (Beta=0.23, t=2.96, p=0.004, CI=0.19-0.95). Our data provides further evidence that DRD4 VNTR polymorphism is associated with OCD. Furthermore, the presence of the 2R allele was significantly associated with the symmetry dimension. This dimension may represent a more homogeneous subtype of OCD with a genetic etiology.