title: Contribution of glucocerebrosidase mutation in a large cohort of sporadic Parkinson's disease in Taiwan.
abstract: OBJECTIVE
  The association between glucocerebrosidase (GBA) mutations and Parkinson's disease (PD) is attracting increased attention worldwide. In patients of Chinese ethnicity, other than the common L444P mutation, a few mutations have been reported. However, the contribution of GBA to PD can be answered only by a thorough investigation of its mutations in a unique large population.
  
  
  METHODS
  We enrolled 1747 participants: 967 PD patients and 780 healthy individuals. We screened entire GBA coding regions and exon-intron boundaries in 30 randomly chosen PD patients, followed by testing five variants (L444P, D409H, R120W, L174P, and Q497R) in all participants. The G2385R and R1628P in LRRK2 had been previously studied in almost all participants.
  
  
  RESULTS
  In total, 36 patients (3.72%) carried a heterozygous mutant GBA allele (27 L444P, 7 RecNciI, and 2 D409H). Only two controls (0.26%) carried heterozygous GBA mutation (1 L444P and 1 RecNciI). In PD group, the mean age at onset in carriers was younger than in non-carriers. The difference in percentage of mutation frequencies between patients and controls was highly significant for the L444P mutation (P < 0.0001). One L444P carrier was also associated with LRRK2 G2385R variant, but no atypical Parkinsonism was observed.
  
  
  CONCLUSIONS
  The present study ascertains that L444P mutation in GBA gene may contribute to an earlier onset of development of PD in Han/Chinese population. Following LRRK2 variants, GBA is the second most frequent mutations indicated for sporadic PD development in the Han/Chinese population. These GBA carriers are associated with an earlier onset of Parkinsonism.
authors.affiliation: Department of Neurology, Saint Paul's Hospital, Taoyuan, Taiwan.
authors.forename: C-L
authors.initials: CL
authors.lastname: Huang
authors.forename: Y-H
authors.initials: YH
authors.lastname: Wu-Chou
authors.forename: S-C
authors.initials: SC
authors.lastname: Lai
authors.forename: H-C
authors.initials: HC
authors.lastname: Chang
authors.forename: T-H
authors.initials: TH
authors.lastname: Yeh
authors.forename: Y-H
authors.initials: YH
authors.lastname: Weng
authors.forename: R-S
authors.initials: RS
authors.lastname: Chen
authors.forename: Y-Z
authors.initials: YZ
authors.lastname: Huang
authors.forename: C-S
authors.initials: CS
authors.lastname: Lu
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000201:enzymology* / Q000208:ethnology / Q000235:genetics*; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult
chemical_list: D005962:Glucosylceramidase