title: Pathogenicity of LRRK2 P755L variant in Parkinson's disease.
abstract: A heterozygous 2264C-->T variant (P755L) in LRRK2 gene has been reported to be a likely pathogenic variant among ethnic Chinese patients with Parkinson's disease (PD). In a case control study, we performed genetic analysis of the P755L variant in an independent cohort of Chinese patients with PD and controls. The P755L variant was present in 4/204 (2.0%) of PD compared with 6/235 (2.6%) of controls (odds ratio = 0.76, 95% CI 0.23, 2.6, P = 0.76). All subjects carried the heterozygous genotype. Subset analysis in the group > or = 65 years of age revealed a prevalence of 2.8% in PD compared with 3.1% in controls (odds ratio = 0.92, 95% CI 022, 3.7, P = 0.9), and in the group < 65 years of age showed a 0% in PD versus 2.1% in controls (P = 0.2). The phenotype of patients with PD with the P755L variant was generally similar to other patients with PD and none of the carriers reported a positive family history. The lack of functional data, absence of segregation of the variant with disease, and the presence of the variant in apparently healthy individuals suggest that P755L is possibly a rare polymorphism in the Chinese population. Further validation of our findings in other populations would be important.
authors.affiliation: Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore. gnrtek@sgh.com.sg
authors.forename: Eng-King
authors.initials: EK
authors.lastname: Tan
authors.forename: Hui-Qin
authors.initials: HQ
authors.lastname: Lim
authors.forename: Yih
authors.initials: Y
authors.lastname: Yuen
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution / Q000235:genetics; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006579:Heterozygote; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D015995:Prevalence; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors; D012846:Singapore / Q000453:epidemiology
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases