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An Exploratory Study

Mario Zappia, MD; Grazia Annesi, PhD; Giuseppe Nicoletti, MD; Gennarina Arabia, MD; Ferdinanda Annesi, PhD; Demetrio Messina, MD; Pierfrancesco Pugliese, MD; Patrizia Spadafora, PhD; Patrizia Tarantino, PhD; Sara Carrideo, PhD; Donatella Civitelli, PhD; Elvira V. De Marco, PhD; Innocenza C. Cirò-Candiano, PhD; Antonio Gambardella, MD; Aldo Quattrone, MD

Arch Neurol. 2005;62:601-605.

Background  Several factors, both clinical and genetic, may account for the risk of developing levodopa-induced peak-dose dyskinesias (PDD) in patients with Parkinson disease, but it is unclear how these factors interact for modulating the individual susceptibility for PDD.

Objective  To examine clinical and genetic risk factors for determining individual susceptibility of PDD in patients with Parkinson disease.

Design  Cohort study.

Setting  Referral center for Parkinson disease in Calabria, southern Italy.

Patients  Two hundred fifty patients with Parkinson disease were screened for the presence or absence of PDD following a short-term levodopa administration, and 215 subjects were available for further evaluations, including genotypic analysis of the CA dinucleotide short tandem repeat (CA_n-STR) polymorphism located in the dopamine receptor D2 gene (DRD2).

Results  One hundred five patients (48.8%) exhibited PDD following short-term levodopa administration, and 110 patients (51.2%) did not. Multivariate logistic regression analysis showed that independent predictors for the occurrence of PDD were female sex, earlier age at onset of Parkinson disease, longer duration of treatment, and higher dose of levodopa. Genetic factors related to the DRD2 CA_n-STR polymorphism were not independent predictors for PDD in the total population, but they had a strong protective effect on the appearance of PDD when the multivariate analysis was performed in men (odds ratio, 0.34 [95% confidence interval, 0.14-0.84]). In women, a genetic protective effect on PDD was not evident.

Conclusions  Risk factors for PDD, both clinical and genetic, act in different ways for men and women. Genetic factors related to the DRD2 polymorphic status have a protective effect on PDD development in men but not in women. A female sex–related effect for the risk of PDD may be so strong that it overcomes any protective effect due to genetic factors.

Author Affiliations: Institute of Neurology, University "Magna Græcia," Catanzaro, Italy (Drs Zappia, Arabia, Pugliese, Gambardella, and Quattrone); Institute of Neurological Sciences, National Research Council, Piano Lago-Cosenza, Italy (Drs Zappia, G. Annesi, Nicoletti, F. Annesi, Messina, Spadafora, Tarantino, Carrideo, Civitelli, De Marco, Cirò-Candiano, and Quattrone).

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