Original Research ARTICLE
Lack of association between DJ-1 gene promoter polymorphism and the risk of Parkinson’s disease
- 1Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China
- 2Institute of Health Sciences, Shanghai Institutes for Biological Sciences (CAS), China
- 3School of Medicine, Shanghai Jiao Tong University, China
Low DJ-1 protein level caused by DJ-1 gene mutation leads to autosomal recessive Parkinson’s disease (PD) due to impaired antioxidative activity. In sporadic PD patients, although mutations were rarely found, lower protein level of DJ-1 was also reported. Dysregulation of DJ-1 gene expression might contribute to low DJ-1 protein level. Since promoter is the most important element to initiate gene expression, whether polymorphisms in DJ-1 promoter result in the dysregulation of gene expression, thus lead to low protein level and cause PD is worth exploring. DJ-1 promoter region was sequenced in a Chinese cohort to evaluate possible links between DJ-1 promoter polymorphisms, PD risk and clinical phenotypes. Related information in existing GWAS database were looked up, meta-analysis of the present study and other previous reports was conducted, and expression quantitative trait loci (eQTL) analysis was performed to further explore the association. Three single nucleotide polymorphisms (SNPs) (rs17523802, rs226249 and rs35675666) and one 18bp deletion polymorphism (rs200968609) were observed in our cohort. However, there was no significant association between the four detected polymorphisms and the risk of PD either in allelic or genotype model, in single-point analysis or haplotype analysis. Searching results in genome-wide association studies (GWAS) meta-analysis database PDGene and meta-analysis of this study and previous reports also showed no significance. In addition, eQTL results in GTEx database demonstrated the lack of association between the four polymorphisms and normal human brain DJ-1 expression level, which further confirmed our results. Thus, DJ-1 promoter polymorphisms may play little role in dysregulation of DJ-1 expression and PD susceptibility, low protein level of DJ-1 may be caused by other reasons.
Keywords: PARK7/DJ-1, Promoter, polymorphism, Parkinson's disease (PD), eQTL
Received: 10 Aug 2018;
Accepted: 28 Jan 2019.
Edited by:Hi-Joon Park, Kyung Hee University, South Korea
Reviewed by:Pau Pastor, Mútua Terrassa University Hospital, Spain
Pawan Gupta, University of Illinois at Chicago, United States
Copyright: © 2019 He, Lin, Pan, Shen, Wang, Liu, Tan, Wang, Chen and Ding. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Dr. Shengdi Chen, Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, email@example.com
Prof. Jianqing Ding, Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, firstname.lastname@example.org