Abstract
(1) Background: Monoamine neurotransmitters play essential roles in the normal functioning of our nervous system. However, the metabolism of monoamine neurotransmitters is accompanied by the production of neurotoxic metabolites, and inefficient removal of the metabolites has been suggested to cause neurodegeneration. (2) Methods: To examine the effect of reduced activity of catechol-O-methyltransferase (COMT) and aldehyde dehydrogenase 2 (ALDH2) conferred by single nucleotide polymorphisms COMT rs4680(A) and ALDH2 rs671(A) on the symptoms of patients with Parkinson’s disease (PD), a total of 114 PD patients were recruited cross-sectionally and received genotyping for rs4680 and rs671 along with MDS-UPDRS evaluation. (3) Results: We found that patients carrying rs4680(A) had more severe bradykinesia in the upper extremity and rest tremor. Besides, patients carrying rs671(A) had more difficulty maintaining personal hygiene, while patients with genotype rs671(GG) had higher scores in the item “depressed mood.” More importantly, we found the effect of rs4680 to be moderated by rs671 SNP for the symptom of “hand movements.” The detrimental impact of rs4680(A) is more pronounced in the presence of genotype rs671(GG). (4) Conclusions: This study facilitates a deeper understanding of the detrimental effect of reduced activity of COMT and ALDH2 conferred by genetic variation and provides novel insight into the interactions between enzymes metabolizing monoamine neurotransmitters in the pathogenesis of PD.
Highlights
Parkinson’s disease (PD) is a neurodegenerative disease characterized by progressive denervation in the striatum and substantia nigra, areas critical for dopamine transmission [1,2,3,4]
Growing evidence has suggested that DOPAL and dihydroxyphenylacetic acid (DOPAC) are associated with neuronal death, and timely removal of the neurotoxic metabolites through enzymatic activity is crucial in reducing the neurotoxicity secondary to monoamine neurotransmitter metabolism [10,11]
To examine the effect of COMT single nucleotide polymorphism (SNP) rs4680(A) on the clinical presentations of patients with PD, we compared the ratings obtained with MDS-UPDRS between PD patients carrying rs4680(A) allele and patients with the genotype of rs4680 (GG)
Summary
Parkinson’s disease (PD) is a neurodegenerative disease characterized by progressive denervation in the striatum and substantia nigra, areas critical for dopamine transmission [1,2,3,4]. It can be presented with a wide range of symptoms, broadly categorized as motor and non-motor symptoms. Growing evidence has suggested that DOPAL and DOPAC are associated with neuronal death, and timely removal of the neurotoxic metabolites through enzymatic activity is crucial in reducing the neurotoxicity secondary to monoamine neurotransmitter metabolism [10,11]. We hypothesized that reduced COMT activity would cause more monoamine neurotransmitters to be metabolized by MAO, resulting in increased production of neurotoxic metabolites [10,11], DOPAL and DOPAC, and the reduced COMT activity would hamper efficient metabolism of DOPAC [12,13]
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