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Updated: Aug 23, 2026

Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease
Published on: January 7, 2014
Planning ability in Parkinson's disease is influenced by the COMT val158met polymorphism
Thomas Foltynie1, Terry E Goldberg, Simon G J Lewis
1Cambridge Centre for Brain Repair, University of Cambridge, United Kingdom. tf210@medschl.cam.ac.uk
Abstract:
Parkinson's disease (PD) patients show a range of executive deficits involving dopaminergic transmission in the prefrontal cortex. In this study, we have investigated the impact of catechol-O-methyl-transferase (COMT) val(158)met polymorphisms on performance of the Tower of London (TOL) test of planning by PD patients. Motor and cognitive assessments were performed on 288 patients as part of a population-based study of PD. These patients were subsequently genotyped for the COMT val(158)met polymorphism. Patients with high activity COMT genotypes performed significantly better at the TOL task than those with low activity genotypes. Subgroup analyses suggest that this effect is greatest in patients exposed to dopaminergic agents. We hypothesise that the inferior performance in patients with the low activity COMT genotype is attributable to a state of relative hyperdopaminergic activity in the dorsolateral prefrontal cortex compared with that in the striatum. We suggest that polymorphisms of common genes, which regulate central nervous system dopaminergic transmission, can influence some of the phenotypic manifestations of PD.
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