Objective: In this study, we aim to elucidate the association between the various haplotypes of the Catechol-O-methyltransferase (COMT) and Monoamine oxidase B (MAO-B) genes, the levodopa daily equivalent (LEDD), and the extent of motor and nonmotor symptoms, in patients with Parkinson’s diseases (PD).

Background: COMT and MAO-B enzymes are pivotal in dopamine breakdown. Gene polymorphisms in these enzymes may alter their activity and influence the efficacy of levodopa in PD patients . [1] Recent research suggests the high-activity COMT haplotype elevates cognitive decline risk in non-demented PD patients. [2] Yet, the impact of these polymorphisms on levodopa dosage, motor, and non-motor symptoms is not fully understood, necessitating further investigation to clarify these associations.

Method: PD patients were annually assessed for LEDD, Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Cognitive Abilities Screening Instrument (CASI), Montreal Cognitive Assessment (MoCA), Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI). Those with the alternative alleles T in rs2020917, G in rs737865, C in rs933271, C in rs4646312, T in rs4633, A in rs4680, A in rs769224, T in rs4646316, T in rs174699, T in rs165728 for COMT and C in rs1799836 for MAO-B were categorized as carriers. Linear mixed models were employed to analysis the temporal effects across clinical scores between the carrier and non-carrier groups.

Results: Initially, 121 PD patients were enrolled, with 78 returning for a 1-year and 49 for a 2-year follow-up. No significant LEDD changes were observed between carriers and non-carriers. For COMT polymorphisms, carriers of rs2020917, rs737865 and rs4646316 had increased UPDRS3 scores (𝛃 = 6.582, p = 0.041; 𝛃 = 6.582, p = 0.041; 𝛃 = 6.619, p = 0.039). Over time, carriers of rs4633 and rs4680 had higher UPDRS4 scores compared to non-carriers (𝛃 = 1.453, p = 0.025; 𝛃 = 1.624, p = 0.012), whereas rs933271 carriers showed lower scores (𝛃 = -1.862, p = 0.004). In MAO-B polymorphisms, rs1799836 carriers had a slower MoCA and CASI score decline (𝛃 = 3.500, p = 0.023; 𝛃 = 7.198, p = 0.027) and reported lower BAI scores (𝛃 = -10.032, p = 0.029).

Conclusion: Distinct polymorphisms in COMT and MAO-B may differently impact motor and non-motor symptoms, without affecting LEDD. This could potentially enable predictions of patient disease progression.

References: [1] Zhao, C., Wang, Y., Zhang, B., Yue, Y., and Zhang, J. (2020). Genetic variations in catechol-O-methyltransferase gene are associated with levodopa response variability in Chinese patients with Parkinson’s disease. Scientific Reports 10(1). doi: 10.1038/s41598-020-65332-2
[2] Lin, C.-H., Fan, J.-Y., Lin, H.-I., Chang, C.-W., and Wu, Y.-R. (2018). Catechol-O-methyltransferase (COMT) genetic variants are associated with cognitive decline in patients with Parkinson’s disease. Parkinsonism & Related Disorders 50, 48-53. doi: 10.1016/j.parkreldis.2018.02.015.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/association-between-genetic-polymorphisms-and-disease-progression-in-parkinsons-disease/