Case-control analysis of LRRK2 protective variants in Essential Tremor

• Published in: Scientific reports Vol. 8; no. 1; pp. 5346 - 4
• Main Authors: Ng, Adeline S. L., Ng, Ebonne Y. L., Tan, Yi Jayne, Prakash, Kumar M., Au, Wing Lok, Tan, Louis C. S., Tan, Eng-King
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.03.2018; Nature Publishing Group
• Subjects: 45; 45/23; 631/208; 692/617/375/346; Family medical history; Genotype & phenotype; Haplotypes; Humanities and Social Sciences; Kinases; Leucine; LRRK2 protein; Movement disorders; multidisciplinary; Mutation; Neurodegenerative diseases; Neurosciences; Parkinson's disease; Pathophysiology; Science; Science (multidisciplinary); Tremor; Tremor (Muscular contraction)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-23711-w

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.