Affiliations: [a] Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| [b] Interdisciplinary Institute of Neuroscience and Technology, Qiushi Academy for Advanced Studies, Zhejiang University, Hangzhou, China
Correspondence to: Baorong Zhang, Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China. E-mail: [email protected].
Note:  These two authors made equal contributions to this report.
Abstract: 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.