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The Potential Mutation of GAK Gene in the Typical Sporadic Parkinson's Disease from the Han Population of Chinese Mainland.

Authors
  • Zhang, Jie1, 2
  • Zeng, Hanyi1
  • Zhu, Lei1
  • Deng, Libing3
  • Fang, Xin1
  • Deng, Xia1
  • Liang, Huiting1
  • Tang, Chunyan1
  • Cao, Xuebing4
  • Lu, Yi1
  • Li, Jiao1
  • Ren, Xiao5
  • Zuo, Wenjie5
  • Zhang, Xiong6
  • Xu, Renshi7
  • 1 Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China. , (China)
  • 2 Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Nanchang University, Nanchang, 330006, Jiangxi, China. , (China)
  • 3 Department of Human Genetics, Institute of Translational Medicine, Nanchang University, Nanchang, 330006, Jiangxi, China. , (China)
  • 4 Department of Neurology, The Affiliated Union Hospital of Huazhong Technological University, Wuhan, 430006, Hubei, China. , (China)
  • 5 Department of Biochemistry and Molecular Biology, the First Clinical Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China. , (China)
  • 6 Department of Neurology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Neuroscience Institute, Guangzhou, 510080, Guangdong, China. [email protected] , (China)
  • 7 Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China. [email protected] , (China)
Type
Published Article
Journal
Molecular neurobiology
Publication Date
Dec 01, 2016
Volume
53
Issue
10
Pages
7119–7136
Identifiers
PMID: 26676575
Source
Medline
Keywords
License
Unknown

Abstract

The genetic factors about the pathogenesis of sporadic Parkinson's disease (sPD) is not completely clear at present; therefore, we performed a genome-wide association study, high-throughput sequencing analysis (HTPSA) of all cyclin G-associated kinase (GAK) exons, loss-of-function assessment, and sorting intolerant from tolerant analysis of HTPSA data in 250 typical sPD and 250 controls, which found 55 candidate single nucleotide polymorphisms (SNPs). To further explore these SNPs, we sequenced the 30 most strongly associated SNPs in the 460 typical sPD cases and the 525 controls. All subjects were from the Han population of Chinese mainland and excluded the toxic exposure, the heavy coffee drinking, and the early- and late-onset sPD. The minor allele frequencies (MAFs) at c.3824T>G, c.3794T>C, and c.3819G>A were higher in the control. The TG of c.3824T>G, the TC of c.3794T>C, and the AG of c.3819G>A were associated with the decreased risk of sPD. The subjects carrying the minor C allele of c.3794T>C or the minor A allele of c.3819G>A exhibited a decreased risk of sPD. c.3824T>G negatively affected the binding affinity of heat shock protein 70 (HSP70). c.3794T>C increased the surface area exposed to substrates. c.3819G>A most likely reduced the expression level of GAK. Our data suggest that the multiple SNPs of GAK synergistically participate in the pathogenesis of sPD through multiple pathways.

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