Genetic variants of LRRK2 in Taiwanese Parkinson's disease

Yih Ru Wu, Kuo Hsuan Chang, Wen Teng Chang, Ya Chin Hsiao, Hsuan Chu Hsu, Pei Ru Jiang, Yi Chun Chen, Chih Ying Chao, Yi Chung Chang, Bo Hsun Lee, Fen Ju Hu, Wan Ling Chen, Guey Jen Lee-Chen, Chiung Mei Chen

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Genetic variants of leucine-rich repeat kinase 2 (LRRK2) were reported to alter the risk for Parkinson's disease (PD). However, the genetic spectrum of LRRK2 variants has not been clearly disclosed yet in Taiwanese population. Herein, we sequenced LRRK2 coding region in 70 Taiwanese early onset PD patients (age at onset = 50), and found six amino acid-changing single nucleotide polymorphisms (SNPs, N551K, R1398H, R1628P, S1647T, G2385R and M2397T), one reported (R1441H) and 2 novel missense (R767H and S885N) mutations. We examined the frequency of identified LRRK2 variants by genotyping 573 Taiwanese patients with PD and 503 age-matched control subjects. The results showed that PD patients demonstrated a higher frequency of G2385R A allele (4.6%) than control subjects (2.1%; odds ratio = 2.27, 95% confidence interval: 1.38-3.88, P = 0.0017). Fewer PD patients (27.7%) carried the 1647T-2397T haplotype as compared with the control subjects (33.0%; odds ratio = 0.80, 95% confidence interval: 0.65-0.97, P = 0.0215). However, the frequency of 1647T-2385R-2397T haplotype (4.3%) in PD patients was still higher than in control subjects (1.9%, odds ratio: 2.15, 95% confidence interval: 1.27-3.78, P = 0.0058). While no additional subject was found to carry R767H and R1441H, one more patient was observed to carry the S885N variant. Our results indicate a robust risk association regarding G2385R and a new possible protective haplotype (1647T-2397T). Gene-environmental interaction and a larger cohort study are warranted to validate our findings. Additionally, two new missense mutations (R767H and S885N) regarding LRRK2 in PD patients were identified. Functional studies are needed to elucidate the effects of these LRRK2 variants on protein function.

Original languageEnglish
Article number0082001
JournalPloS one
Volume8
Issue number12
DOIs
Publication statusPublished - 2013 Dec 5

Fingerprint

Parkinson disease
Leucine
leucine
Parkinson Disease
phosphotransferases (kinases)
Phosphotransferases
odds ratio
Haplotypes
confidence interval
haplotypes
Odds Ratio
Confidence Intervals
Single Nucleotide Polymorphism
missense mutation
Missense Mutation
Polymorphism
cohort studies
genotyping
single nucleotide polymorphism
Cohort Studies

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Wu, Y. R., Chang, K. H., Chang, W. T., Hsiao, Y. C., Hsu, H. C., Jiang, P. R., ... Chen, C. M. (2013). Genetic variants of LRRK2 in Taiwanese Parkinson's disease. PloS one, 8(12), [0082001]. https://doi.org/10.1371/journal.pone.0082001

Genetic variants of LRRK2 in Taiwanese Parkinson's disease. / Wu, Yih Ru; Chang, Kuo Hsuan; Chang, Wen Teng; Hsiao, Ya Chin; Hsu, Hsuan Chu; Jiang, Pei Ru; Chen, Yi Chun; Chao, Chih Ying; Chang, Yi Chung; Lee, Bo Hsun; Hu, Fen Ju; Chen, Wan Ling; Lee-Chen, Guey Jen; Chen, Chiung Mei.

In: PloS one, Vol. 8, No. 12, 0082001, 05.12.2013.

Research output: Contribution to journalArticle

Wu, YR, Chang, KH, Chang, WT, Hsiao, YC, Hsu, HC, Jiang, PR, Chen, YC, Chao, CY, Chang, YC, Lee, BH, Hu, FJ, Chen, WL, Lee-Chen, GJ & Chen, CM 2013, 'Genetic variants of LRRK2 in Taiwanese Parkinson's disease', PloS one, vol. 8, no. 12, 0082001. https://doi.org/10.1371/journal.pone.0082001
Wu YR, Chang KH, Chang WT, Hsiao YC, Hsu HC, Jiang PR et al. Genetic variants of LRRK2 in Taiwanese Parkinson's disease. PloS one. 2013 Dec 5;8(12). 0082001. https://doi.org/10.1371/journal.pone.0082001
Wu, Yih Ru ; Chang, Kuo Hsuan ; Chang, Wen Teng ; Hsiao, Ya Chin ; Hsu, Hsuan Chu ; Jiang, Pei Ru ; Chen, Yi Chun ; Chao, Chih Ying ; Chang, Yi Chung ; Lee, Bo Hsun ; Hu, Fen Ju ; Chen, Wan Ling ; Lee-Chen, Guey Jen ; Chen, Chiung Mei. / Genetic variants of LRRK2 in Taiwanese Parkinson's disease. In: PloS one. 2013 ; Vol. 8, No. 12.
@article{80c81e1d39b341f88a80877820f8b954,
title = "Genetic variants of LRRK2 in Taiwanese Parkinson's disease",
abstract = "Genetic variants of leucine-rich repeat kinase 2 (LRRK2) were reported to alter the risk for Parkinson's disease (PD). However, the genetic spectrum of LRRK2 variants has not been clearly disclosed yet in Taiwanese population. Herein, we sequenced LRRK2 coding region in 70 Taiwanese early onset PD patients (age at onset = 50), and found six amino acid-changing single nucleotide polymorphisms (SNPs, N551K, R1398H, R1628P, S1647T, G2385R and M2397T), one reported (R1441H) and 2 novel missense (R767H and S885N) mutations. We examined the frequency of identified LRRK2 variants by genotyping 573 Taiwanese patients with PD and 503 age-matched control subjects. The results showed that PD patients demonstrated a higher frequency of G2385R A allele (4.6{\%}) than control subjects (2.1{\%}; odds ratio = 2.27, 95{\%} confidence interval: 1.38-3.88, P = 0.0017). Fewer PD patients (27.7{\%}) carried the 1647T-2397T haplotype as compared with the control subjects (33.0{\%}; odds ratio = 0.80, 95{\%} confidence interval: 0.65-0.97, P = 0.0215). However, the frequency of 1647T-2385R-2397T haplotype (4.3{\%}) in PD patients was still higher than in control subjects (1.9{\%}, odds ratio: 2.15, 95{\%} confidence interval: 1.27-3.78, P = 0.0058). While no additional subject was found to carry R767H and R1441H, one more patient was observed to carry the S885N variant. Our results indicate a robust risk association regarding G2385R and a new possible protective haplotype (1647T-2397T). Gene-environmental interaction and a larger cohort study are warranted to validate our findings. Additionally, two new missense mutations (R767H and S885N) regarding LRRK2 in PD patients were identified. Functional studies are needed to elucidate the effects of these LRRK2 variants on protein function.",
author = "Wu, {Yih Ru} and Chang, {Kuo Hsuan} and Chang, {Wen Teng} and Hsiao, {Ya Chin} and Hsu, {Hsuan Chu} and Jiang, {Pei Ru} and Chen, {Yi Chun} and Chao, {Chih Ying} and Chang, {Yi Chung} and Lee, {Bo Hsun} and Hu, {Fen Ju} and Chen, {Wan Ling} and Lee-Chen, {Guey Jen} and Chen, {Chiung Mei}",
year = "2013",
month = "12",
day = "5",
doi = "10.1371/journal.pone.0082001",
language = "English",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

TY - JOUR

T1 - Genetic variants of LRRK2 in Taiwanese Parkinson's disease

AU - Wu, Yih Ru

AU - Chang, Kuo Hsuan

AU - Chang, Wen Teng

AU - Hsiao, Ya Chin

AU - Hsu, Hsuan Chu

AU - Jiang, Pei Ru

AU - Chen, Yi Chun

AU - Chao, Chih Ying

AU - Chang, Yi Chung

AU - Lee, Bo Hsun

AU - Hu, Fen Ju

AU - Chen, Wan Ling

AU - Lee-Chen, Guey Jen

AU - Chen, Chiung Mei

PY - 2013/12/5

Y1 - 2013/12/5

N2 - Genetic variants of leucine-rich repeat kinase 2 (LRRK2) were reported to alter the risk for Parkinson's disease (PD). However, the genetic spectrum of LRRK2 variants has not been clearly disclosed yet in Taiwanese population. Herein, we sequenced LRRK2 coding region in 70 Taiwanese early onset PD patients (age at onset = 50), and found six amino acid-changing single nucleotide polymorphisms (SNPs, N551K, R1398H, R1628P, S1647T, G2385R and M2397T), one reported (R1441H) and 2 novel missense (R767H and S885N) mutations. We examined the frequency of identified LRRK2 variants by genotyping 573 Taiwanese patients with PD and 503 age-matched control subjects. The results showed that PD patients demonstrated a higher frequency of G2385R A allele (4.6%) than control subjects (2.1%; odds ratio = 2.27, 95% confidence interval: 1.38-3.88, P = 0.0017). Fewer PD patients (27.7%) carried the 1647T-2397T haplotype as compared with the control subjects (33.0%; odds ratio = 0.80, 95% confidence interval: 0.65-0.97, P = 0.0215). However, the frequency of 1647T-2385R-2397T haplotype (4.3%) in PD patients was still higher than in control subjects (1.9%, odds ratio: 2.15, 95% confidence interval: 1.27-3.78, P = 0.0058). While no additional subject was found to carry R767H and R1441H, one more patient was observed to carry the S885N variant. Our results indicate a robust risk association regarding G2385R and a new possible protective haplotype (1647T-2397T). Gene-environmental interaction and a larger cohort study are warranted to validate our findings. Additionally, two new missense mutations (R767H and S885N) regarding LRRK2 in PD patients were identified. Functional studies are needed to elucidate the effects of these LRRK2 variants on protein function.

AB - Genetic variants of leucine-rich repeat kinase 2 (LRRK2) were reported to alter the risk for Parkinson's disease (PD). However, the genetic spectrum of LRRK2 variants has not been clearly disclosed yet in Taiwanese population. Herein, we sequenced LRRK2 coding region in 70 Taiwanese early onset PD patients (age at onset = 50), and found six amino acid-changing single nucleotide polymorphisms (SNPs, N551K, R1398H, R1628P, S1647T, G2385R and M2397T), one reported (R1441H) and 2 novel missense (R767H and S885N) mutations. We examined the frequency of identified LRRK2 variants by genotyping 573 Taiwanese patients with PD and 503 age-matched control subjects. The results showed that PD patients demonstrated a higher frequency of G2385R A allele (4.6%) than control subjects (2.1%; odds ratio = 2.27, 95% confidence interval: 1.38-3.88, P = 0.0017). Fewer PD patients (27.7%) carried the 1647T-2397T haplotype as compared with the control subjects (33.0%; odds ratio = 0.80, 95% confidence interval: 0.65-0.97, P = 0.0215). However, the frequency of 1647T-2385R-2397T haplotype (4.3%) in PD patients was still higher than in control subjects (1.9%, odds ratio: 2.15, 95% confidence interval: 1.27-3.78, P = 0.0058). While no additional subject was found to carry R767H and R1441H, one more patient was observed to carry the S885N variant. Our results indicate a robust risk association regarding G2385R and a new possible protective haplotype (1647T-2397T). Gene-environmental interaction and a larger cohort study are warranted to validate our findings. Additionally, two new missense mutations (R767H and S885N) regarding LRRK2 in PD patients were identified. Functional studies are needed to elucidate the effects of these LRRK2 variants on protein function.

UR - http://www.scopus.com/inward/record.url?scp=84891944313&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84891944313&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0082001

DO - 10.1371/journal.pone.0082001

M3 - Article

C2 - 24339985

AN - SCOPUS:84891944313

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 12

M1 - 0082001

ER -