Haplotype Analysis on the Relationship of the DNAJC6 Gene with Early-Onset Parkinson’s Disease Risk in a Chinese Population

Autor:	Jun Tian, Ting Shen, Hsin Yi Lai, Yaping Yan, Jiali Pu, Yanxin Chen, Baorong Zhang, Yasi Jiang, Shuai Zhao
Rok vydání:	2019
Předmět:	Adult Male Risk 0301 basic medicine China In silico Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide 03 medical and health sciences Cellular and Molecular Neuroscience Exon 0302 clinical medicine Genetic variation Humans SNP Age of Onset Gene Aged Genetics Multifactor dimensionality reduction Haplotype Parkinson Disease HSP40 Heat-Shock Proteins Middle Aged 030104 developmental biology Haplotypes Female Neurology (clinical) 030217 neurology & neurosurgery
Zdroj:	Journal of Parkinson's Disease. 9:109-120
ISSN:	1877-718X 1877-7171
Popis:	BACKGROUND DNAJC6 gene is one of the Parkinson's disease (PD) related genes, but relationship between DNAJC6 polymorphisms and PD remains unclear. OBJECTIVE We aims to examine the association between genetic variations in DNAJC6 gene and idiopathic early-onset PD (EOPD) in the Chinese population. METHODS Exons and intron/exon boundaries of DNAJC6 gene was amplified and sequenced in 135 EOPD patients and 212 healthy controls. Single nucleotide polymorphisms (SNP)-based and haplotype-based association study between EOPD and DNAJC6 was conducted. SNP-SNP interactions were investigated using the generalized multifactor dimensionality reduction (GMDR) method. We further evaluated the effect of variants on gene function and expression using online in silico algorithms and databases. RESULTS We found fourteen previously reported SNPs in the DNAJC6 gene. The frequencies of variant alleles in rs11208644, rs4582839 and rs4915691 were observed significantly higher in EOPD group compared to healthy controls, while in rs6588144 was significantly lower. Additionally, haplotype analysis indicated that the CTCACTCGGC, CTTACTCGGC and TTTGTTCGAC haplotypes were associated with higher EOPD risk in EOPD patients. SNP-SNP interaction analysis showed that rs12077111-rs4592284 SNP combination was the best model with higher EOPD risk. Based on the in silico analysis results, these SNPs were predicted to be no harm to the protein function, but might lead to possible changes in splice site and alter the expression level of DNAJC6. CONCLUSION Our study indicated that EOPD was associated with several SNPs and haplotypes of DNAJC6 gene.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::12b98a2baa743a4e04029ec50ba02af9 https://doi.org/10.3233/jpd-181411 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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