SynthesisNeurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology2022
Polymorphisms of the dopamine metabolic and signaling pathways are associated with susceptibility to motor levodopa-induced complications (MLIC) in Parkinson's disease: a systematic review and meta-analysis.
Synthesis in Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Does COMT Play a Role in Parkinson's Disease Susceptibility across Diverse Ancestral Populations?Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Multigenetic pharmacogenomics-guided treatment shows greater improvements on motor symptoms compared to usual therapy in Parkinson's disease: a small real-word prospective cohort study.Frontiers in pharmacology · 2025Article
- Elucidating the role of APOE ε4 gene variants in the clinical manifestation of Parkinson's disease.Frontiers in aging neuroscience · 2025Article
- Safinamide as an Adjunct to Levodopa in Asian and Caucasian Patients With Parkinson's Disease and Motor Fluctuations: A Post Hoc Analysis of the SETTLE Study.Journal of movement disorders · 2023Article
- Association of Catechol-O-Methyltransferase Gene Polymorphisms and Haplotypes in the Levodopa-Induced Adverse Events in Subjects with Parkinson's Disease.Indian journal of clinical biochemistry : IJCB · 2023Article
- Effects of MAO-B inhibitors on non-motor symptoms and quality of life in Parkinson's disease: A systematic review.NPJ Parkinson's disease · 2022Article
- A Roadmap for Future Parkinson's Pharmacogenomics in Asia.Frontiers in aging neuroscience · 2022Article
- Genetic architecture of Parkinson's disease subtypes - Review of the literature.Frontiers in aging neuroscience · 2022Review
- Bipolar disorder and subsequent Parkinson's disease: a meta-analysis of cohort studies.Frontiers in neurologyReview
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDopamine replacement therapy remains the gold standard for symptomatic management of Parkinson's disease worldwide. However, most patients will develop debilitating motor levodopa-induced complications (MLIC) in the form of levodopa-induced dyskinesia (LID) and/or motor fluctuations (MF). This study aimed to conduct a systematic review and meta-analysis on the pharmacogenetic association between LID and MF with common genetic variants of the dopamine metabolic and signaling pathways.
methodsA meta-analysis was conducted according to the PRISMA guidelines. Extracted studies include case-control studies evaluating the association between SLC6A3/DAT rs28363170 and rs393795; COMT rs4680 and rs4633; MAO-B rs1799836, BDNF rs6265, DRD1 rs4532, DRD2 rs1800497, DRD3 rs6280, and DRD5 rs6283 polymorphisms; and the overall risk of MLIC and its subtypes LID or MF. Genotypic frequency were tested for deviation from the Hardy-Weinberg equilibrium (HWE), and the genetic association was examined using the allelic (a vs. A), recessive (aa vs. Aa + AA), dominant (aa + Aa vs. AA), overdominant (Aa vs. aa + AA), homozygous (aa vs. AA), and heterozygous (Aa vs. AA and aa vs. aA) models.
resultsFourteen studies were included in the meta-analysis. A significant association was found between COMT rs46809 polymorphisms with LID but not MF, with the association observable in Asians but not Caucasians. In Asians, the COMT rs4633 was significantly associated with the occurrence of both LID and MF. The MAO-B rs1799836 was associated with both MF and LID. Among all the dopamine receptor genes analyzed, only DRD2 exhibited an association with LID. No association was observed between the SLC6AT/DAT and BDNF genes with either LID or MF.
conclusionStrong associations were observed between polymorphisms of genes regulating dopamine metabolism with the occurrence of LID and/or MF. The MAO-B rs1799836 may be potential for use as a general pharmacogenetic marker of MLIC, while the COMT rs4680 and rs4633 may be used as markers of LID in Asian ethnicities.
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