Sex Differences in Clinical and Genetic Determinants of Levodopa Peak-Dose Dyskinesias in Parkinson Disease: An Exploratory Study

• Published in: Archives of neurology (Chicago) Vol. 62; no. 4; pp. 601 - 605
• Main Authors: Zappia, Mario, Annesi, Grazia, Nicoletti, Giuseppe, Arabia, Gennarina, Annesi, Ferdinanda, Messina, Demetrio, Pugliese, Pierfrancesco, Spadafora, Patrizia, Tarantino, Patrizia, Carrideo, Sara, Civitelli, Donatella, De Marco, Elvira V, Cirò-Candiano, Innocenza C, Gambardella, Antonio, Quattrone, Aldo
• Format: Journal Article
• Language: English
• Published: Chicago, IL American Medical Association 01.04.2005
• Subjects: Age of Onset; Aged; Antiparkinson Agents - adverse effects; Biological and medical sciences; Clinical outcomes; Cohort Studies; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA Mutational Analysis; DNA Repeat Expansion - genetics; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Dyskinesia, Drug-Induced - genetics; Dyskinesia, Drug-Induced - metabolism; Dyskinesia, Drug-Induced - physiopathology; Female; Gender differences; Genetic Predisposition to Disease - genetics; Genetic Testing; Genotype; Health risk assessment; Humans; Levodopa - adverse effects; Male; Medical sciences; Multivariate Analysis; Neurology; Parkinson Disease - drug therapy; Parkinson's disease; Pharmacology. Drug treatments; Polymorphism, Genetic - genetics; Predictive Value of Tests; Receptors, Dopamine D2 - genetics; Sex Characteristics; Toxicity: nervous system and muscle; Nervous system diseases; Central nervous system disease; Sex; Parkinson disease; Degenerative disease; Levodopa; Neurological disorder; Cerebral disorder; Extrapyramidal syndrome; Involuntary movement; Dyskinesia
• ISSN: 0003-9942; 2168-6149; 1538-3687; 2168-6157
• DOI: 10.1001/archneur.62.4.601

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 (CAn-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 CAn-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.Arch Neurol. 2005;62:601-605-->