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

研究成果: 雜誌貢獻文章

24 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
文章編號0082001
期刊PloS one
8
發行號12
DOIs
出版狀態已發佈 - 2013 十二月 5
對外發佈Yes

ASJC Scopus subject areas

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

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    Wu, Y. R., Chang, K. H., Chang, W. T., Hsiao, Y. C., Hsu, H. C., Jiang, P. R., Chen, Y. C., Chao, C. Y., Chang, Y. C., Lee, B. H., Hu, F. J., Chen, W. L., Lee-Chen, G. J., & 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