title: Lrrk2 R1628P variant is a risk factor for essential tremor.
abstract: Essential tremor (ET) and Parkinson's disease (PD) are two of the most common adult onset movement disorders with overlapping clinical features. PD patients with leucine-rich repeat kinase-2 (LRRK2) mutations may present initially with an ET phenotype. To address the possibility of a common genetic link between ET and PD, we examined the association between a common LRRK2 R1628P gene variant and ET. The LRRK2 R1628P was genotyped in ET cases and matched healthy controls. A total of 1277 subjects comprising of 450 ET cases and 827 controls were included. There were 40 heterozygote (GG to CG) variant out of 450 ET cases (genotypic frequency 8.9%) and 36 heterozygote variant (GG to CG, genotypic frequency 4.3%) and one homozygote variant (GG to CC) out of 827 controls. Subjects carrying the R1628P variant had a twofold increased risk of ET (p = 0.0035, OR = 2.20 and 95% confidence interval is 1.30-3.73). Using a case control methodology, we demonstrated an association between a known PD risk variant, LRRK2 R1628P, with ET. Subjects carrying the R1628P variant had twice the risk of developing ET. The sharing of a similar gene risk variant suggests a possible pathophysiologic link between PD and ET.
authors.affiliation: 1] Departments of Neurology, Singapore General Hospital [2] National Neuroscience Institute.
authors.forename: Yin Xia
authors.initials: YX
authors.lastname: Chao
authors.affiliation: 1] Departments of Neurology, Singapore General Hospital [2] National Neuroscience Institute.
authors.forename: Ebonne Yulin
authors.initials: EY
authors.lastname: Ng
authors.affiliation: National Neuroscience Institute.
authors.forename: Louis
authors.initials: L
authors.lastname: Tan
authors.affiliation: Departments of Neurology, Singapore General Hospital.
authors.forename: Kumar M
authors.initials: KM
authors.lastname: Prakash
authors.affiliation: National Neuroscience Institute.
authors.forename: Wing-Lok
authors.initials: WL
authors.lastname: Au
authors.affiliation: Clinical Research, Singapore General Hospital.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: 1] Departments of Neurology, Singapore General Hospital [2] Clinical Research, Singapore General Hospital [3] National Neuroscience Institute [4] Duke-NUS Graduate Medical School.
authors.forename: Eng-King
authors.initials: EK
authors.lastname: Tan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D020329:Essential Tremor / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D010300:Parkinson Disease / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases