1. Higher urate in LRRK2 mutation carriers resistant to Parkinson disease
- Author
-
Eric A. Macklin, Michael A. Schwarzschild, Rachit Bakshi, Grace F. Crotty, Ning Xia, Robert Logan, Alberto Ascherio, Xiqun Chen, Ellen Zhang, and Musab M. Zorlu
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Plasma samples ,business.industry ,Disease ,Disease pathogenesis ,Age and sex ,Gastroenterology ,Penetrance ,LRRK2 ,Mean difference ,nervous system diseases ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Neurology ,Internal medicine ,Cohort ,medicine ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
OBJECTIVE LRRK2 mutations, the most common genetic cause of Parkinson disease (PD), display incomplete penetrance, indicating the importance of other genetic and environmental influences on disease pathogenesis in LRRK2 mutation carriers. The present study investigates whether urate, an antioxidant, Nrf2 activator, and inverse risk factor for idiopathic PD, is one such candidate biomarker of PD risk modulation in pathogenic LRRK2 mutation carriers. METHODS Banked plasma samples or urate levels were obtained for 3 cohorts of age- and sex-matched subjects with and without a known LRRK2 mutation in PD and unaffected controls to conduct a pilot study of 192 subjects from the LRRK2 Cohort Consortium (LCC) and 2 validation studies of 380 additional subjects from the LCC and 922 subjects from the Parkinson's Progression Markers Initiative. Urate levels were compared by multiple regression between subjects with and without a PD diagnosis conditional on LRRK2 status, controlling for age and sex. RESULTS Nonmanifesting LRRK2 mutation carriers had significantly higher levels of urate than those who developed PD in each of the 3 independent cohorts. A meta-analysis demonstrated an adjusted mean difference of 0.62 mg/dL (p
- Published
- 2019
- Full Text
- View/download PDF