title: Parkin polymorphisms and environmental exposure: decrease in age at onset of Parkinson's disease.
abstract: We tested the hypothesis that parkin polymorphisms (SNPs) and environmental exposure (EE) interact to reduce the age of onset of idiopathic Parkinson disease (PD). We prospectively and consecutively enrolled a total of 81 Italian PD patients. The diagnosis of PD was based on the UK Parkinson's Disease Society's brain bank criteria. Twenty-one patients with a positive family history for PD or tremor were excluded from the study. We collected information about medical history and EE. PARK1, PARK2 genes and PARK8 (exon 41) were screened. We detected one parkin mutation in a single patient and three parkin polymorphisms in a total of 25 patients; no alpha synuclein mutations, no common mutations of LRKK2 gene were found. The mutation-positive patient has been excluded from the study. The cohort of the remaining 59 patients has been divided into four subgroups, according to the presence/absence of parkin polymorphisms and the presence/absence of environmental factors-exposure. The age of onset of PD was significantly lower in patients with both SNPs and EE as compared to patients without (62.18+/-9.5 years versus 71.62+/-8 years, p=0.024; -13%). Patients with either SNPs or EE had an intermediate age of onset. The association of parkin polymorphisms and environmental exposure has a strong effect in lowering the age of onset of PD; the effect of environmental exposure or parkin polymorphisms alone seems to influence modestly the age of onset of PD. Individuals with environmental/occupational exposure should be screened for the presence of parkin SNPs.
authors.affiliation: Centro per il Morbo di Parkinson, Centro Dino Ferrari, Department of Neurological Sciences, University of Milan, Fondazione I.R.C.C.S., Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Ghione
authors.forename: Alessio
authors.initials: A
authors.lastname: Di Fonzo
authors.forename: Francesca
authors.initials: F
authors.lastname: Saladino
authors.forename: Roberto
authors.initials: R
authors.lastname: Del Bo
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Giacomo Pietro
authors.initials: GP
authors.lastname: Comi
authors.forename: Mario
authors.initials: M
authors.lastname: Rango
mesh_terms: D017668:Age of Onset; D000368:Aged; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D009154:Mutation / Q000235:genetics / Q000502:physiology; D010300:Parkinson Disease / Q000453:epidemiology* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000502:physiology*; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D004247:DNA; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein