Sex differences in clinical and genetic determinants of levodopa peak-dose dyskinesias in Parkinson disease: an exploratory study.
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.


METHODS
Cohort study.


METHODS
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.
Zappia
Mario
M
Institute of Neurology, University ''Magna Graecia,'' Catanzaro, Italy.
Annesi
Grazia
G
Nicoletti
Giuseppe
G
Arabia
Gennarina
G
Annesi
Ferdinanda
F
Messina
Demetrio
D
Pugliese
Pierfrancesco
P
Spadafora
Patrizia
P
Tarantino
Patrizia
P
Carrideo
Sara
S
Civitelli
Donatella
D
De Marco
Elvira V
EV
Cirò-Candiano
Innocenza C
IC
Gambardella
Antonio
A
Quattrone
Aldo
A
D017668:Age of Onset; D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D042622:DNA Repeat Expansion / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D015999:Multivariate Analysis; D010300:Parkinson Disease / Q000188:drug therapy*; D011110:Polymorphism, Genetic / Q000235:genetics; D011237:Predictive Value of Tests; D017448:Receptors, Dopamine D2 / Q000235:genetics; D012727:Sex Characteristics
D000978:Antiparkinson Agents; D017448:Receptors, Dopamine D2; D007980:Levodopa