Objective: To explore the association of psychosis in Parkinson’s disease with polymorphisms of HOMER1, a gene whose product (Homer1) is responsible for modulating the metabotropic glutamate receptor.

Background: Psychosis is one of the debilitating non-motor symptoms of Parkinson’s disease (PD) which commonly manifests through minor hallucinations (such as passage hallucinations, presence hallucinations, and illusions) and well-formed visual hallucinations. Although polymorphisms of several genes have been explored, the genetic substrates of psychosis in PD remains incompletely understood. Homer1 is a protein with a crucial function in glutamate transmission, which has a potential role in the genesis of hallucinations.

Method: This study recruited a total of 150 Indian subjects- 50 patients with psychosis (PD-P), 50 patients without psychosis (PD-NP), and 50 controls. The groups were matched for age, gender, and education. Single nucleotide polymorphism (SNP) genotyping assay was done by real-time polymerase chain reaction (RT-PCR). Two SNPs of the HOMER1 gene (rs4704559, rs4704560) were studied.

Results: There was no significant difference between any of the genotypes of rs4704559 (AG, GG, AA) between the controls and the overall patient group. Similarly, there was no difference in the frequency of the A and G alleles between the two groups. Similar to the comparison between controls and overall PD group, there was no significant difference between PD-P and PD-NP neither at the genotype level nor at the allele level. For HOMER1-rs4704560 (CC, CT, TT), there was a significant difference in the genotype level as well as in the allele level comparison between PD-P and PD-NP. There was an over-representation of the T-allele of HOMER1-rs4704560 in the PD-P group (p<0.001, Odd’s ratio: 2.62).

Conclusion: The PD-P group had a higher frequency of T-allele compared to the PD-NP group (p<0.001, Odd’s ratio: 2.62). Although previous studies did not find any association of this polymorphism with psychosis in PD, a positive result in our study certainly raises the possibility that T-allele is a risk factor for psychosis in Indian PD patients. This result also reinforces the fact that alterations in the glutamate transmission may have a certain role in the pathogenesis of psychosis in PD.

References: 1) Lenka et.al., Genetic substrates of psychosis in patients with Parkinson’s disease: A critical review; J Neurol Sci. 2016 May 15;364:33-41. 2) Schumacher-Schuh et.al., Association of common genetic variants of HOMER1 gene with levodopa adverse effects in Parkinson’s disease patients. Pharmacogenomics J. 2014 Jun;14(3):289-94.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/homer1-polymorphism-in-patients-with-parkinsons-disease-and-psychosis/