Dopamine D
            <sub>2</sub>
            receptor gene polymorphism and the risk of levodopa-induced dyskinesias in PD

Oliveri, R. L.; Annesi, Grazia; Zappia, Mario; Civitelli, Donatella; Montesanti, R.; Branca, Damiano; Nicoletti, Giuseppe; Spadafora, Patrizia; Pasqua, Angela Aurora; Cittadella, Rita; Andreoli, Virginia; Gambardella, Antonio; Aguglia, Umberto; Quattrone, Aldo

doi:10.1212/wnl.53.7.1425

Cited by 103 publications

(71 citation statements)

References 36 publications

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“…Female gender, earlier age at onset of PD and a longer duration of levodopa therapy have been associated with a higher risk of developing peakdose dyskinesias [49]. Genetic factors could also contribute to individual variability in the development of peak-dose dyskinesias.…”

Section: Polymorphisms Associated With Drug Tolerancementioning

confidence: 99%

Pharmacogenetics of Antiparkinsonian Drug Treatment: A Systematic Review

et al. 2007

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Pharmacotherapy is the mainstay in the treatment of Parkinson’s disease and the armamentarium of drugs available for the therapy of this disease is still expanding. Anti-Parkinson’s disease drugs are effective in reducing the physical symptoms, such as hypokinesia, bradykinesia, rigidity and tremor. However, there is a large interindividual variability in response to anti-Parkinson’s disease drugs with respect to both drug efficacy and toxicity. It is thought that genetic variability in genes encoding drug-metabolizing enzymes, drug receptors and proteins involved in pathway signaling is an important factor in determining interindividual variability in drug response. Pharmacogenetics aims at identifying genetic markers associated with drug response. Ideally, knowledge of these genetic markers will enable us to predict an individual’s drug response in terms of both efficacy and toxicity. The role of pharmacogenetics in the treatment of Parkinson’s disease is relatively unexplored. Therefore, we aim to present a systematic review of the published pharmacogenetic studies in Parkinson’s disease and to describe polymorphic genes of interest for future research.

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Section: Polymorphisms Associated With Drug Tolerancementioning

confidence: 99%

Pharmacogenetics of Antiparkinsonian Drug Treatment: A Systematic Review

et al. 2007

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“…Interestingly, both studies found that the DRD2 gene was involved in the development of different types of motor complications, namely, wearing off and PDD. These results suggest that the DRD2 gene might play a pivotal role 20,189 in the genetic susceptibility to the motor complications induced by levodopa in PD, but this should be further examined.…”

Section: Pharmacodynamics: Dopamine Receptorsmentioning

confidence: 93%

“…nor was there an association of smoking and PD risk with the presence of these polymorphisms. The remaining four studies examined the polymorphic dinucleotide repeat in the second intron of the DRD2 gene, [17][18][19][20] but only two of them 18,20 found a significant association between this polymorphism and PD in Caucasians.…”

Section: Genetic Variations With Potential Effect On Pd Risk: Dopaminmentioning

confidence: 99%

“…Oliveri et al 20 were the first to address the possibility that polymorphisms in the genes for DRD1 and DRD2 could be implicated in the appearance of PDD after long-term levodopa use. They found that the frequencies of the 13 and 14 alleles of the DRD2 gene polymorphism were higher in nondyskinetic than in dyskinetic PD patients.…”

Section: Pharmacodynamics: Dopamine Receptorsmentioning

confidence: 99%

“…The risk reduction of developing PDD for PD patients carrying at least one of the 13 or 14 alleles was 72% with respect to PD subjects who did not carry these alleles. 20 Another study investigated the association between DRD2 and DRD3 gene polymorphisms and the risk of developing motor fluctuations in PD. 189 The authors found that the TaqIA polymorphism located in the DRD2 gene may influence the risk of developing 'wearing off' motor fluctuations.…”

Section: Pharmacodynamics: Dopamine Receptorsmentioning

confidence: 99%

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

et al. 2004

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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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Sex Differences in Clinical and Genetic Determinants of Levodopa Peak-Dose Dyskinesias in Parkinson Disease

Zappia¹,

Annesi²,

Nicoletti³

et al. 2005

Arch Neurol

188

107

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Dopamine D ₂ receptor gene polymorphism and the risk of levodopa-induced dyskinesias in PD

Abstract: Certain alleles of the short tandem repeat polymorphism of the dopamine receptor D2 gene reduce the risk of developing peak-dose dyskinesias and could contribute to varying susceptibility to develop peak-dose dyskinesias during levodopa therapy.

Cited by 103 publications

References 36 publications

Pharmacogenetics of Antiparkinsonian Drug Treatment: A Systematic Review

Pharmacogenetics of Antiparkinsonian Drug Treatment: A Systematic Review

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

Sex Differences in Clinical and Genetic Determinants of Levodopa Peak-Dose Dyskinesias in Parkinson Disease

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Dopamine D 2 receptor gene polymorphism and the risk of levodopa-induced dyskinesias in PD

Abstract: Certain alleles of the short tandem repeat polymorphism of the dopamine receptor D2 gene reduce the risk of developing peak-dose dyskinesias and could contribute to varying susceptibility to develop peak-dose dyskinesias during levodopa therapy.

Cited by 103 publications

References 36 publications

Pharmacogenetics of Antiparkinsonian Drug Treatment: A Systematic Review

Pharmacogenetics of Antiparkinsonian Drug Treatment: A Systematic Review

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

Sex Differences in Clinical and Genetic Determinants of Levodopa Peak-Dose Dyskinesias in Parkinson Disease

Contact Info

Product

Resources

About

Dopamine D ₂ receptor gene polymorphism and the risk of levodopa-induced dyskinesias in PD