HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Data Supplement Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kaiser, R. Articles by Brockmöller, J. Search for Related Content PubMed PubMed Citation Articles by Kaiser, R. Articles by Brockmöller, J. Related Collections Parkinson's disease/Parkinsonism All Toxicology Association studies in genetics

L -Dopa-induced adverse effects in PD and dopamine transporter gene polymorphism

From the Institute of Clinical Pharmacology (Drs. Kaiser, Hofer, Grapengiesser, Roots, and Brockmöller) and Department of Neurology (Dr. Kupsch), Charité, Humboldt-Universität zu Berlin; Department of Clinical Pharmacology (Drs. Kaiser and Brockmöller), Georg-August-Universität Göttingen; and Department of Neurology (Dr. Gasser), Klinikum Großhadern, Ludwig-Maximilians-Universität München, Germany.

Address correspondence and reprint requests to Dr. R. Kaiser, Abteilung Klinische Pharmakologie, Universitätsklinikum der Georg-August-Universität Göttingen, Robert Koch Str. 40, D-37075, Göttingen, Germany; e-mail: rolf.kaiser{at}med.uni-goettingen.de

Objective: To assess whether polymorphisms in the dopamine receptor genes and in the dopamine transporter gene (DAT ) are predictors of adverse effects of L -dopa.

Methods: A retrospective noninterventional study with 183 patients with PD was conducted. Nine polymorphisms of the dopamine D2 receptor (DRD2 ), two of the dopamine D3 receptor (DRD3 ), three of the dopamine D4 receptor (DRD4 ), and one variable number of tandem repeats (VNTR) of the DAT were studied. The entire coding and promoter regions of the DRD2 gene of 48 patients with early and severe appearance of adverse effects from L -dopa treatment and of eight never-afflicted patients were sequenced.

Results: The polymorphisms of DRD2 , DRD3 , and DRD4 were not associated with the risk to develop adverse effects of L -dopa. However, patients with psychosis or dyskinesia carried the nine copy allele 40–bp VNTR of the DAT more frequently than nonafflicted patients (60.0 vs 36.8%, p = 0.008; and 54.7 vs 32.9%, p = 0.006). Sequencing of the DRD2 gene revealed no new mutation, with the exception of one silent mutation in exon 6.

Conclusions: Genetic variations of the DRD2 , DRD3 , and DRD4 do not influence the occurrence of L -dopa-induced adverse effects. However, the nine copy allele 40–bp VNTR of the DAT is a predictor for the occurrence of psychosis or dyskinesia in L -dopa-treated patients.

This article has been cited by other articles:

				D. Paleacu, E. Schechtman, and R. Inzelberg Association between family history of dementia and hallucinations in Parkinson disease Neurology, May 24, 2005; 64(10): 1712 - 1715. [Abstract] [Full Text] [PDF]

				More on Psychosis in Parkinson Disease Journal Watch Neurology, September 25, 2003; 2003(925): 5 - 5. [Full Text]

				More on Psychosis in Parkinson's Disease Journal Watch Psychiatry, September 3, 2003; 2003(903): 4 - 4. [Full Text]