Association between obsessive compulsive disorder and the COMT gene

Obsessive compulsive disorder (OCD) is a clinical condition characterized by persistent, unwanted thoughts and ritualistic behaviours. Data from families and segregation studies strongly support the hypothesis of a genetic liability. Catechol-O-methyltransferase (COMT) is a key modulator of catecholaminergic neurotransmission. Recently, a significant association between a common functional polymorphism (Met 158 Val) in the coding sequence of COMT, resulting in a three to fourfold reduction in enzyme activity, and susceptibility for OCD was found, particularly in males. We decided to investigate a sample of OCD patients, diagnosed according to DSM IV criteria, for a possible association with COMT alleles using a haplotype relative risk (HER) strategy. We collected 49 nuclear families of OCD probands (26 males, 23 females) of Italian descent. The distribution of both genotypes and alleles was not significantly different between male and female OCD patients (P = 0.365 for genotypes; P = 0.950 for alleles). Furthermore, allele frequencies in the OCD sample (high activity allele = 0.55; low activity allele = 0.45) are not different from those reported in the literature for Caucasians. HRR analysis produced negative results in the total sample (P = 0.4444) as well as subdivided the sample according to the sex of the proband (P = 0.8320 for males; P = 0.9765 for females). Our study failed to confirm the previous finding of an association between the COMT low activity allele and male OCD.