Sexually dimorphic relationship of a 5-HT2A promoter polymorphism with obsessive-compulsive disorder

Background: In an earlier analysis of 73 subjects from this study, the reduced activity catechol O-methyltransferase variant was shown to be associated with obsessive–compulsive disorder in men only. We hypothesized that the 5-HT2A promoter polymorphism, -1438G>A, previously associated with anorexia nervosa, would be more abundant in women with obsessive-compulsive disorder. Methods: One hundred and one Caucasian obsessive–compulsive disorder patients (48 women, 53 men) and 138 control subjects (77 women, 61 men), were genotyped. DSM-III-R psychiatric diagnoses were assigned based on the SCID-I. Results: As hypothesized, the -1438A allele frequency was higher in obsessive-compulsive disorder women (.57) than female control subjects (.42) (p = .015). The genotype frequencies were also significantly different (p = .020). Allele frequencies did not differ between male obsessive-compulsive disorder patients (.44) and male control subjects (.41). Conclusions: We have found that a 5-HT2A promoter polymorphism is associated with obsessive-compulsive disorder in women but not in men, strengthening the argument that there may be fundamental gender differences in the genetic susceptibility to obsessive-compulsive disorder.