Objective: This study aimed to find the association of genetic variations between Parkinson’s disease (PD) patients with and without levodopa-induced dyskinesia (LID). we intended to find the frequency of a single nucleotide polymorphism (SNP) rs1799836 in monoamine oxidase B (MAO-B) gene and a 40bp variable number tandem repeat (VNTR) in 3’UTR of SLC6A3 (DAT1) gene and studied their association with clinical parameters of the disease.

Background: The pathogenesis of LID in PD remains unclear. Recent studies are suggestive of a strong genetic linkage for LID development among PD patients. The role of pharmacogenomics in the pathophysiology of LID is less explored. The genes for dopamine receptor, transporter and catabolic enzyme functioning carry genetic variations that may alter levodopa response among PD patients.

Method: 200 clinically characterized PD patients (100 without LID, 100 with LID) and 100 age-matched healthy controls were recruited from the outpatient department of Institute of Neurosciences Kolkata, India. Clinical scales were performed for estimation of severity of motor features and LID respectively in the ON state of the disease. Participants were analyzed for the presence of polymorphisms and VNTR by polymerase chain reaction followed by restriction fragment length polymorphism techniques.

Results: MAO-B variant rs1799836, G allele was more frequently present than A allele in PD patients with LID compared to PD patients without LID (P=0.003; OR= 2.30, 95% CI: 1.29-4.09). The abnormal involuntary movement score (AIMS) was significantly higher in PD patients with G allele (AG+GG) compared to carriers of A allele (4.41±2.40; P=0.003). DAT1 10R/9R type of repeat variant was more frequently present than other alleles in PD patients with LID compared to PD patients without LID (P=0.004; OR= 0.45, 95% CI: 0.25-0.80). AIMS score was significantly higher in PD patients with 10R/9R allele (3.86±3.37; p=0.005).

Conclusion: We observed a significant association of G allele of MAO-B gene (rs1799836) and 10R/9R variant of SLC6A3 (DAT1) gene with LID in our cohort of Indian PD patients. The interindividual variation in PD patients to develop LID could be related to genetic variations and hence these SNPs could be potential targets for precision medicine.

References: [1] Kakinuma, S., et al., Monoamine oxidase B rs1799836 G allele polymorphism is a risk factor for early development of levodopa-induced dyskinesia in Parkinson’s disease. ENeurologicalSci, 2020. 19: p. 100239.

[2] Purcaro, C., et al., DAT gene polymorphisms (rs28363170, rs393795) and levodopa-induced dyskinesias in Parkinson’s disease. Neuroscience Letters, 2019. 690: p. 83-88.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/genetic-variants-and-levodopa-response-in-parkinsons-disease-insights-from-mao-b-and-dat1-polymorphisms/