No abstract

In recent years, the molecular etiology of parkinsonism has yielded to genetic analysis.1 Mutations in the gene leucine-rich repeat kinase 2 (LRRK2) have the highest genotypic and population attributable risk. Disparate penetrance estimates have been reported using a variety of statistical analyses, ethnic populations, and sample sizes.2 We compared the age-associated cumulative incidence (penetrance) of LRRK2 p.G2019S patients from Tunisia and Norway.Methods. Clinic-based population series. The Tunisian Arab-Berber series includes 350 patients with idiopathic Parkinson disease (iPD) (mean onset 55.3 6 14.3 years, range 12-83). An additional 220 are affected LRRK2 p.G2019S carriers (mean onset 57.1 6 11.6 years, range 22-82); 12 unaffected LRRK2 carriers were also identified (mean age 56.7 6 10.9 years). A total of 411 control subjects (spouses or unrelated individuals) were recruited through the Clinic and genotyped. Neither blood relatives of cases nor control subjects were included. The ethnic Norwegian series includes 443 with iPD (mean onset 58.8 6 11.2 years, range 25-88). A total of 520 control subjects (mostly spouses or unrelated individuals) were recruited through the Clinic and genotyped. In Norway, an additional 27 are affected LRRK2 p.G2019S carriers (mean onset 63 6 11.6 years, range 40-82) and 57 unaffected carriers were identified (mean age of 54.2 6 15.2 years) as first-to third-degree relatives through field studies. 3All individuals, clinical data, and blood samples were obtained with local ethical approvals, independently reviewed by the University of British Columbia Research Ethics Board. Written informed consent was provided. Neurologists specializing in movement disorders (F.H. and J.O.A.) diagnosed patients using UK Brain Bank criteria 4 for both the Tunisian and Norwegian populations. Age at onset was obtained from patient medical records or by selfreport. DNA was extracted from blood; LRRK2 genotyping was verified by Sanger sequencing. 5Statistical analysis. The penetrance was estimated for iPD and LRRK2 carriers using a Kaplan-Meier method (JMP software, SAS Institute Inc., Cary, NC) with age at onset as the time variable; asymptomatic carriers were right-censored at the age at last contact or age at death, using log-rank tests to assess significance.

The effect of environmental and lifestyle factors on patients with LRRK2 (leucine-rich repeat kinase 2) p.Gly2019Ser (LRRK2 + / PD +) compared to idiopathic PD (iPD) has yet to be thoroughly investigated. Methods: In a homogeneous Tunisian Arab Berber population, we recruited 200 idiopathic PD and 199 LRRK2 p.Gly2019Ser mutation carriers, of whom 142 had PD (LRRK2 + /PD +) and 57 were unaffected (LRRK2 + /PD −). Case report form (CRF) questionnaires (motor and non-motor symptoms) including the Geoparkinson Questionnaire were used to assess environmental and lifestyle factors. Results: In LRRK2 + /PD + , tobacco use was significantly associated with a later median age at onset (AAO). The median AAO was 60 years (interquartile range = 52-67.25) for tobacco users, compared to 52 years (interquartile range = 45.25-61) for non-users (P = 0.0042 at adjusted α = 0.025). Additionally, we observed an independent but additive effect of black tea consumption and tobacco use. Conclusions: Our data suggest that tobacco and black tea have a protective effect on age at onset in LRRK2 + /PD + .