Contribution of glucocerebrosidase mutation in a large cohort of sporadic Parkinson's disease in Taiwan

C. L. Huang, Yah Huei Wu-Chou, S. C. Lai, H. C. Chang, T. H. Yeh, Yi H. Weng, R. S. Chen, Y. Z. Huang, C. S. Lu

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background and purpose: 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.

Original languageEnglish
Pages (from-to)1227-1232
Number of pages6
JournalEuropean Journal of Neurology
Volume18
Issue number10
DOIs
Publication statusPublished - Oct 2011
Externally publishedYes

Fingerprint

Glucosylceramidase
Taiwan
Parkinson Disease
Mutation
Parkinsonian Disorders
Population
Mutation Rate
Age of Onset
Introns
Exons
Alleles

Keywords

  • GBA gene
  • LRRK2
  • Sporadic Parkinson's disease
  • Taiwanese

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Contribution of glucocerebrosidase mutation in a large cohort of sporadic Parkinson's disease in Taiwan. / Huang, C. L.; Wu-Chou, Yah Huei; Lai, S. C.; Chang, H. C.; Yeh, T. H.; Weng, Yi H.; Chen, R. S.; Huang, Y. Z.; Lu, C. S.

In: European Journal of Neurology, Vol. 18, No. 10, 10.2011, p. 1227-1232.

Research output: Contribution to journalArticle

Huang, CL, Wu-Chou, YH, Lai, SC, Chang, HC, Yeh, TH, Weng, YH, Chen, RS, Huang, YZ & Lu, CS 2011, 'Contribution of glucocerebrosidase mutation in a large cohort of sporadic Parkinson's disease in Taiwan', European Journal of Neurology, vol. 18, no. 10, pp. 1227-1232. https://doi.org/10.1111/j.1468-1331.2011.03362.x
Huang, C. L. ; Wu-Chou, Yah Huei ; Lai, S. C. ; Chang, H. C. ; Yeh, T. H. ; Weng, Yi H. ; Chen, R. S. ; Huang, Y. Z. ; Lu, C. S. / Contribution of glucocerebrosidase mutation in a large cohort of sporadic Parkinson's disease in Taiwan. In: European Journal of Neurology. 2011 ; Vol. 18, No. 10. pp. 1227-1232.
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abstract = "Background and purpose: 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.",
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AU - Huang, C. L.

AU - Wu-Chou, Yah Huei

AU - Lai, S. C.

AU - Chang, H. C.

AU - Yeh, T. H.

AU - Weng, Yi H.

AU - Chen, R. S.

AU - Huang, Y. Z.

AU - Lu, C. S.

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N2 - Background and purpose: 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.

AB - Background and purpose: 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.

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