Objective: To investigate if polymorphisms of the HOMER1 and COMT gene are associated with psychosis in Parkinson’s disease (PD).

Background: Psychosis is one of the debilitating non-motor symptoms (NMS) of PD. However, the precise neural correlates of psychosis in PD (PD-P) remain elusive. Several lines of evidence indicate that the pathogenesis of PD-P is multifactorial and genetic polymorphism is one such factor. This study investigated the association of HOMER1 (rs4704559 and rs4704560) and COMT (rs4680) polymorphism with PD-P in Indian patients. Homer, a protein encoded by HOMER1, is considered part of a mechanism of homeostatic plasticity that dampens the neuronal responsiveness when input activity is too high. COMT codes for the enzyme catechol-o-methyl transferase, which is crucial for levodopa metabolism. rs4680 of COMT results in a 3 to 4-fold decrease in COMT enzyme activity (increase prefrontal dopamine).

Method: One hundred patients with PD and 100 healthy controls were enrolled in a PD-P biomarker study at the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. Of those 100 PD patients, 50 had psychosis (PD-P), and 50 did not have psychosis (PD-NP). The patient and the control groups were matched for age and gender. Two single nucleotide polymorphisms (SNPs) of HOMER1 and one SNP of COMT (as mentioned above) were analyzed from the DNA isolated from the peripheral blood. The allele and genotype frequencies in PD-P and PD-NP group were compared.

Results: Analysis of the HOMER1 rs4704560 revealed a significant difference in genotype level and the allele level comparison between PD-P and PD-NP. There was over-representation of the T-allele (42% vs. 16%; p< 0.001) and TT genotype (24% vs. 6%; p<0.001) in the PD-P group compared to PD-NP. There was no significant difference between PD-P and PD-NP on comparing various genotype and allele frequencies related to HOMER1 rs4704559 and COMT rs4680.

Conclusion: Overexpression of the T-allele of HOMER1 rs4704560 is associated with psychosis in PD patients. HOMER1 rs4704559 and COMT rs4680 were not associated with psychosis in our PD patients.

References: Lenka et.al. 2016. Genetic substrates of psychosis in patients with Parkinson’s disease: A critical review; J Neurol Sci.2016 May 15; 364:33-41. doi: 10.1016/j.jns.2016.03.005

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MDS Abstracts - https://www.mdsabstracts.org/abstract/psychosis-in-parkinsons-disease-and-polymorphisms-of-the-homer1-and-comt-genes-is-there-an-association/