Correlations Between Methionine Cycle Metabolism, COMT Genotype, and Polyneuropathy in L-Dopa Treated Parkinson’s Disease: A Preliminary Cross-Sectional Study
Affiliations: [a] Department of Neurology, Karolinska University Hospital Huddinge, Stockholm, Sweden
| [b] Department of Clinical Neuroscience, Translational Neuropharmacology, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden
Correspondence:
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Correspondence to: Per Svenningsson, Department of Clinical Neuroscience, Translational Neuropharmacology, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden. Tel.: +46 851774614; E-mail: per.svenningsson@ki.se and Mattias Andréasson, Department of Neurology, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden. Tel.: +46 858580000; E-mail: mattias.andreasson@sll.se.
Abstract: Background:Polyneuropathy (pnp) is recognized as a clinical feature of Parkinson’s disease (PD). Whether pnp is a result of the alpha-synucleinopathy or related to treatment is debated. Previous studies support underlying disturbances in the methionine cycle mediated by L-dopa. Objective:Describe possible relationships between methionine cycle metabolism and the development of pnp in L-dopa treated PD. Furthermore, we aim to investigate possible genetic risk factors by genotyping specific SNPs in enzymes involved in the abovementioned pathways. Methods:In a cross-sectional study design, L-dopa treated PD patients (n = 33) and controls (n = 16) were evaluated with biochemical and genetic analyses. Subjects were assessed clinically and with regards to signs of pnp using established clinical neuropathy rating scales. Results:16/33 patients fulfilled a study diagnosis of pnp compared to 0 age-matched controls. Levels of homocysteine (Hcy) were significantly higher in patients with pnp (n = 16) compared to controls. A significant correlation between neuropathy scores and Hcy was seen in the whole patient group (n = 33). A significant difference in the genotype distribution of the COMT A158G polymorphism was demonstrated, favoring the low activity genotype in patients with pnp compared to both controls and patients without pnp. Conclusions:Pnp is a prevalent condition in L-dopa treated PD and an association may exist with elevated levels of Hcy, possibly reflecting an underlying impaired cellular methylation capacity. Furthermore, an association may exist between the low activity COMT genotype and pnp. These preliminary findings and the suggested pathophysiological mechanisms should be confirmed in future large-scale studies.
