Abstract
Co-existence of Parkinson’s disease (PD) and essential tremor (ET) may reflect overlapping pathophysiology underlying both conditions. Furthermore, PD patients with leucine-rich repeat kinase-2 (LRRK2) mutations may present with ET-like features, suggesting the possibility of common genetic underpinnings. Two common LRRK2 variants, R1398H and N551K, have been shown to be protective in multiple PD cohorts. We hypothesized that R1398H and N551K may show a similar effect in ET. In a case-control study involving 3198 subjects (2680 controls and 518 ET cases), R1398H was detected in 16.6% of ET cases compared to 18.0% in controls (OR = 0.91, 95% CI = 0.71–1.17, p = 0.46); while N551K was detected in 16.5% of ET cases compared to 18.0% of controls (OR = 0.89, 95% CI = 0.69–1.15, p = 0.37). While these results suggest that LRRK2 R1398H or N551K do not appear to modulate the risk of ET, it remains possible that a protective trend for both variants may be present in ET and a much larger sample size is required to identify this.
Highlights
Essential tremor (ET) is a common movement disorder characterized mainly by postural and kinetic tremor of the upper extremities
Childhood-onset essential tremor (ET) who later developed Parkinson’s disease (PD), had their PD-related rest tremor typically starting ipsilateral to the side of the more severe ET tremor[9]
Several epidemiological studies have demonstrated an association between ET and PD greater than expected in the general population[11,12], suggesting the possibility of overlapping molecular and/or genetic links underpinning both diseases
Summary
Essential tremor (ET) is a common movement disorder characterized mainly by postural and kinetic tremor of the upper extremities. Mutations in the leucine-rich repeat kinase-2 (LRRK2) gene are the most common cause of familial PD, and PD patients with LRRK2 mutations have been reported to present initially with an ET-like phenotype[4], raising the possibility of a genetic link between PD and ET. Two polymorphic LRRK2 variants rs7133914 (R1398H) and rs7308720 (N551K), both in linkage disequilibrium, were previously reported to confer up to 20% reduction in risk of PD in Chinese patients[5], the protective effect of which has been replicated in other Asian cohorts[5,6]. Given the possibility of shared genetic links between ET and PD, we conducted a case-control analysis to investigate if the apparent protective effect of the LRRK2 R1398H and N551K variants would be seen in our cohort of patients with ET
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
