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Polymorphism in candidate genes: implications for the risk and treatment of idiopathic Parkinson's disease

ABSTRACT

Idiopathic Parkinson's disease (IPD) is a progressive neurodegenerative disorder for which no restorative or neuroprotective therapy is available. Interest has recently been directed to association studies on polymorphisms of various genes, mainly those related to dopamine metabolism and transport, and their effect on response to PD, which includes primarily levodopa and dopaminomimetics. Approximately 15–20% of patients with PD do not respond to levodopa, and the majority of those who do respond develop adverse fluctuations in motor response, primarily levodopa-induced dyskinesias. This review summarizes the influence of polymorphisms in various genes on the relative risk of IPD and on levodopa efficacy. It focuses on the importance of well-designed polymorphism studies that include large samples of patients with IPD and tightly matched controls and use identical methodologies. Valid data on such polymorphisms might increase the efficacy of levodopa, decrease its side effects, and reduce the occurrence of levodopa-induced dyskinesias. They might also provide a novel diagnostic tool for PD.

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Acknowledgements

This work was supported in part by the Israel Ministry of Health (DO), the National Parkinson Foundation, USA (EM), and the Norma and Alan Aufzein Chair for Research in Parkinson's Disease, Tel Aviv University, Israel. We thank Gloria Ginzach and Charlotte Sachs of the Editorial Board and also Yossef S Levy, Rabin Medical Center, Beilinson Campus, for their assistance.

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Gilgun-Sherki, Y., Djaldetti, R., Melamed, E. et al. Polymorphism in candidate genes: implications for the risk and treatment of idiopathic Parkinson's disease. Pharmacogenomics J 4, 291–306 (2004). https://doi.org/10.1038/sj.tpj.6500260

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