The relationship between COMT genotype and the clinical effectiveness of tolcapone, a COMT inhibitor, in patients with Parkinson's disease

Patients with Parkinson's Disease (PD) have a variable response to tolcapon e, a catechol-O-methyltransferase (COMT) inhibitor. In addition, a subset o f patients develop severe diarrhea as a side effect. Two codominant alleles for the COMT gene exist, coding for low and high activity, resulting in lo w-, medium-, and high-activity genotypes. This study investigates the relat ionship between this variation in genotype and clinical effects in patients with PD taking tolcapone. To investigate the relationship between COMT pol ymorphism and clinical response, 24 patients who completed tolcapone clinic al trials provided blood samples for COMT genotype analysis. Change in levo dopa dose and United Parkinson Disease Rating Scare (UPDRS) Part III (motor subscale) were analyzed at baseline, at 1-2 weeks, and 6 months after init iation of tolcapone. Genotype analysis was performed on seven patients who had diarrhea as a side effect. There was no significant correlation between genotype and improvement in UPDRS score (p = 0.29) according to a linear m odels approach that adjusted for the subject's severity of PD, tolcapone do se (either 100 or 200 mg three times daily) and initial differences in base line scores. No significant difference was seen in change in daily levodopa intake and genotype. There was also no relation between diarrhea and COMT genotype. These results indicate that, in the treatment of Parkinson's dise ase, COMT genotype is not a major contributor to the clinical response to t olcapone.