Polymorphisms of dopamine receptor genes and risk of visual hallucinations in Parkinson’s patients

• Published in: European journal of clinical pharmacology 2016-11, Vol.72 (11), p.1335-1341
• Main Authors: Ferrari, M, Comi, C, Marino, F, Magistrelli, L, De Marchi, F, Cantello, R, Riboldazzi, G, Bono, G, Cosentino, M
• Format: Article
• Language: English
• Subjects: Aged; Alleles; Biomedical and Life Sciences; Biomedicine; Case-Control Studies; Female; Genetics; Genotype; Hallucinations; Hallucinations - etiology; Hallucinations - genetics; Humans; Male; Middle Aged; Odds Ratio; Parkinson Disease - complications; Parkinson Disease - epidemiology; Parkinson Disease - genetics; Parkinson's disease; Pharmacogenetics; Pharmacology/Toxicology; Receptors, Dopamine - genetics; Risk; Studies
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-016-2111-4

Background Visual hallucinations (VHs) are frequent non-motor complication of Parkinson’s disease (PD), associated to a negative prognosis. Previous studies showed an association between dopamine receptor (DR) gene ( DR ) variants and psychosis in Alzheimer’s disease, addictions, schizophrenia, and bipolar disorder. However, there are only a few studies on DR variants and VHs in PD, which did not provide conclusive results. Objectives The present study aimed to determine whether genetic differences of DR are associated with visual hallucinations (VHs) in a cohort of Parkinson’s disease (PD) patients. Methods A case-control study of 84 PD subjects, 42 with and 42 without VHs,that were matched for age, gender, disease duration, and dopaminergic medication was conducted. Polymerase chain reaction for SNPs in both D1-like ( DRD1 A-48G [rs4532] and C62T [rs686], DRD5T798C [rs6283]) and D2-like DR ( DRD2 G2137A [rs1800497] and C957T [rs6277], DRD3 G25A [rs6280] and G712C [rs1800828], DRD4 C616G [rs747302] and nR VNTR 48bp) analyzed genomic DNA. Results Patients carrying allele T at DRD1 C62T had an increased risk of VHs, expressed as OR (95 % CI, p value), of 10.7 (2.9–40, p  = 0.0001). Moreover, patients with DRD1 -48 GG and 62TT genotype displayed shorter time to VHs, whereas a longer time to VHs was found in subjects carrying the DRD4 CG alleles. Conclusions PD patients with VHs display higher frequency of DR SNPs associated with increased D1-like activity and decreased D2-like activity. Our data are in line with associations reported in other neurodegenerative and psychiatric conditions. Results likely provide valuable information for personalizing pharmacological therapy in PD patients.