Critical Review of Pharmacogenomics in Antiparkinsonian Drug Therapy: Impact on Clinical Management of Parkinson’s Disease

Abstract

Objective: Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder characterized by rest tremors, bradykinesia, rigidity, postural instability, gait dysfunction, and several non-motor symptoms. The marked difference in drug response and adverse effect profile among patients led to search of genetic markers and polymorphism associated with response to antiparkinsonian drugs which will enable us to predict an individual's response to drugs in terms of both efficacy and toxicity. Hence, efforts to define the role of genetic polymorphism in optimizing pharmacotherapy of PD have been undertaken and some promising genetic loci for the treatment have been determined. Therefore, we aim to present a critical review of pharmacogenetic aspects of levodopa, dopamine agonists (DAs), and catecol-O-methyltransferase (COMT) inhibitors and describe gene polymorphism of interest for future research. Methods:The PubMed database was searched using the keywords "parkinsonism," "antiparkinsonian drugs," "levodopa," "DAs," "COMT inhibitors," "pharmacogenomics," and "polymorphism." Abstracts and review articles were included for the study. Results and Conclusion:Studies conducted in different settings suggest that pharmacogenomics plays a significant role in Parkinsonism drug therapy. The gene/drug pairings with the strongest potential for pharmacogenetic recommendations include COMT allele/levodopa and entacapone, dopamine D2 receptor (DRD2)/ropinirole, pramipexole, and DRD3/ropinirole and pramipexole. It can be concluded that with the rapid development of genotyping platforms, genome-wide association study can be performed to analyze polymorphism associated with inefficient treatment or adverse effects. Hence, individualized therapy of PD for better patient care can be achieved by targeted genetic testing.