Objective: This study is aimed to explore the relationship between the single nucleotide polymorphisms (SNPs) in dopamine and serotonin metabolism genes, other neurotransmitter systems genes and genes for abnormal plasticity and PD levodopa-induced motor complications.

Background: It is assumed that genetic mechanisms play an important role in the development of PD levodopa-induced motor complications (dyskinesias and fluctuations).

Method: We investigated 674 sporadic PD patients. Duration of disease, duration of levodopa treatment, levodopa equivalent daily dose (LEDD) was determined, motor fluctuations (“on-off”) and levodopa-induced dyskinesia was assessed in all 300 patients. Levodopa-induced motor complications are estimated using of MDS-UPDRS scale (parts IV). The analysis of 22 SNPs of SLC6A3, DRD1-DRD4, 5-HTT, HTR1B, HTR2A, HTR2C, COMT, TPH, GRIN2A, ADORA2A, BDNF, HOMER1 genes was performed. The SPSS software (multivariate linear regression analysis) was used for statistical analysis.

Results: The combination rs2298383*ADORA2A*T+rs3892097*CYP2D6*A+rs4680*COMT*A+rs1800532*TPH1*G correlated with the severity of dyskinesias from MDS-UPDRS-IV score (p=0,01, β=1,58 95%CI 0,73–2,91) according with the time of onset of dyskinesias after the start of levodopa (p=2,4×10^-8, β=0,28 95%CI 0,19 – 0,38) and the daily equivalent dose of levodopa (p=1,5х10^-3, β=0,007 95%CI 0,0004–0,001).

The severity of motor fluctuations correlated with rs3761422*ADORA2A (p=0,037, β=-0,54 95%CI -1,05 – -0,03) according with the duration of taking levodopa (p=2,36×10^-8, β=0,25 95%CI 0,16 – 0,33) and the equivalent dose of levodopa (p=4,2х10^-5, β=0,001 95%CI 0,0007 – 0,002).

The severity of levodopa-induced motor complications speed development of dyskinesias after the start of levodopa correlated with rs6318*HTR2C*С (p=0,038, β=1,24 95%CI 0,03–2,88) according with the total dose antiparkinsonian drugs (p=0,0002, β=0,21 95%CI 0,098–0,33), the equivalent dose of levodopa (p=0,0001, β=0,002 95%CI 0,001–0,003) and speed development of dyskinesias after the start of levodopa (p=0,004, β=0,37 95%CI 0,12–0,61).

Conclusion: So, certain alleles of dopamine and serotonin metabolism genes, other neurotransmitter systems genes and genes for abnormal plasticity could be genetic risk factors for the PD levodopa-induced motor complications development. This study continues.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-study-of-genetic-factors-in-levodopa-induced-motor-complications-development-in-russian-patients-with-parkinsons-disease/