Association between the dopamine D2 receptor TaqI A2 allele and low activity COMT allele with obsessive–compulsive disorder in males

Abstract

Background: Mounting evidence suggests the involvement of the dopamine system in the pathophysiology of obsessive-compulsive disorder. Method: The relationship of the dopamine D 2 receptor (DRD2) TaqI A, and catechol-O-methyltransferase (COMT) NlaIII High/Low activity polymorphism to obsessive-compulsive disorder (OCD) was examined in a sample of 150 patients and 150 controls. Results: OCD patients did not show significant differences in genotype distribution and allele frequency for polymorphisms investigated relative to controls. However, when the sample was stratified by gender, there was a trend to a significant predominance of the DRD2 A2A2 genotype ( p = 0.049), and a higher frequency of the DRD2 A2 allele ( p = 0.020) and low-activity COMT allele ( p = 0.035) in male OCD patients compared to male controls. In addition, we observed an association of the DRD2 A2A2 genotype in patients with an early onset of disease (V15 years) ( p = 0.033). Conclusions: Our findings replicate previous reports and provide support for a potential role of the COMT and DRD2 locus in subgroup of male, early onset patients with OCD.

Catechol-O-Methyltransferase (COMT): A Gene Contributing to Sex Differences in Brain Function, and to Sexual Dimorphism in the Predisposition to Psychiatric Disorders

“…They showed that the low-activity (Met 158 ) allele was associated with OCD in men, but not in women. The finding was replicated in a family-based study (Karayiorgou et al, 1999), and in three out of four subsequent case control studies (Poyurovsky et al, 2005;Denys et al, 2006;Pooley et al, 2007). The sex-selective effect of COMT in OCD was confirmed in a meta-analysis (Pooley et al, 2007); the odds ratio associated with the Met 158 allele in men was 1.88 (po0.001), with no effect in women (odds ratio 0.98, p ¼ 0.83), and with a significant sex difference between the odds ratios (po0.0001).…”

Gender differences in obsessive-compulsive disorder: a literature review

“…On the other hand, OCD in women, but not in men, was associated with the A allele of the -1438G>A polymorphism of the promoter region of 5-HT2A 50 and the short allele of 5-HTTLPR. 51 However Wendland et al 52 found no association between OCD, gender and three other functional polymorphisms of the serotonin transporter gene (5-HTTLPR, STin2, and rs25531), 52 despite using a larger sample than the one used by Denys et al, 53 which also found an association between the short allele of 5-HTTLPR and women with OCD. 53 Dickel et al 54 also found an association between woman with OCD and the 5-HTTLPR long allele polymorphism, although, after correction for multiple testing, the finding lost significance.…”

Estudos de associação genética no transtorno obsessivo-compulsivo

“…OCD can also be heterogeneous between genders. Several genetic association studies showed there were differences when analyzed separately by gender 16,17,51,85,101,[146][147][148][149][150][151][152][153][154][155] . The same is seen when the sample is divided according to age at onset of TOC 18,20,56,68,86,153,156 .…”

“…In another study, Nicolini et al found an association between the A allele of the DRD2 TaqIA2 (p = 0.01) and TOC and an excess of homozygotes A2A2 in OCD + tics group (p = 0.001) 50 . Denys et al found a higher frequency of the DRD2 A2 allele only in men with OCD (p = 0.02) 51 (Table 2). …”