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Sex differences in clinical and genetic determinants of levodopa peak-dose dyskinesias in Parkinson disease: an exploratory study.
Arch Neurol. 2005 Apr; 62(4):601-5.AN

Abstract

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.

Authors+Show Affiliations

Institute of Neurology, University ''Magna Graecia,'' Catanzaro, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

15824260

Citation

Zappia, Mario, et al. "Sex Differences in Clinical and Genetic Determinants of Levodopa Peak-dose Dyskinesias in Parkinson Disease: an Exploratory Study." Archives of Neurology, vol. 62, no. 4, 2005, pp. 601-5.
Zappia M, Annesi G, Nicoletti G, et al. Sex differences in clinical and genetic determinants of levodopa peak-dose dyskinesias in Parkinson disease: an exploratory study. Arch Neurol. 2005;62(4):601-5.
Zappia, M., Annesi, G., Nicoletti, G., Arabia, G., Annesi, F., Messina, D., Pugliese, P., Spadafora, P., Tarantino, P., Carrideo, S., Civitelli, D., De Marco, E. V., Cirò-Candiano, I. C., Gambardella, A., & Quattrone, A. (2005). Sex differences in clinical and genetic determinants of levodopa peak-dose dyskinesias in Parkinson disease: an exploratory study. Archives of Neurology, 62(4), 601-5.
Zappia M, et al. Sex Differences in Clinical and Genetic Determinants of Levodopa Peak-dose Dyskinesias in Parkinson Disease: an Exploratory Study. Arch Neurol. 2005;62(4):601-5. PubMed PMID: 15824260.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sex differences in clinical and genetic determinants of levodopa peak-dose dyskinesias in Parkinson disease: an exploratory study. AU - Zappia,Mario, AU - Annesi,Grazia, AU - Nicoletti,Giuseppe, AU - Arabia,Gennarina, AU - Annesi,Ferdinanda, AU - Messina,Demetrio, AU - Pugliese,Pierfrancesco, AU - Spadafora,Patrizia, AU - Tarantino,Patrizia, AU - Carrideo,Sara, AU - Civitelli,Donatella, AU - De Marco,Elvira V, AU - Cirò-Candiano,Innocenza C, AU - Gambardella,Antonio, AU - Quattrone,Aldo, PY - 2005/4/13/pubmed PY - 2005/5/11/medline PY - 2005/4/13/entrez SP - 601 EP - 5 JF - Archives of neurology JO - Arch Neurol VL - 62 IS - 4 N2 - 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. SN - 0003-9942 UR - https://www.unboundmedicine.com/medline/citation/15824260/Sex_differences_in_clinical_and_genetic_determinants_of_levodopa_peak_dose_dyskinesias_in_Parkinson_disease:_an_exploratory_study_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/archneur.62.4.601 DB - PRIME DP - Unbound Medicine ER -