Abstract

BackgroundDJ-1 has been thought as a candidate biomarker for Parkinson’s disease (PD). It was found reduced in PD brains, CSF and saliva, although there were conflicting results. How DJ-1 expression may be regulated is not clear. Recently, blood-based DNA methylation represents a highly promising biomarker for PD by regulating the causative gene expression. Thus, in this study, we try to explore whether blood-based DNA methylation of DJ-1 could be used as a biomarker to differentiate PD patients from normal control (NC), and whether DNA methylation could regulate DJ-1 expression in a SH-SY5Y cell model.MethodsForty PD patients and 40 NC were recruited in this study. DNA was extracted from peripheral blood leukocytes (PBLs). Methylation status of two CpG islands (CpG1 and CpG2) in promoter region of DJ-1 was explored by bisulfite specific PCR-based sequencing method. Methylation inhibitor 5-Aza-dC was used to treat SH-SY5Y cell line, DJ-1 level was detected in both mRNA and protein level.ResultsCpG sites in these two CpG islands (CpG1 and CpG2) of DJ-1 were unmethylated in both PD and NC group. In SH-SY5Y cell model treated by methylation inhibitor, there was no significant change of DJ-1 expression in either mRNA level or protein level.ConclusionsOur results indicated that DNA methylation inhibitor didn’t alter DJ-1 gene expression in SH-SY5Y cell model, and DNA methylation of DJ-1 promoter region in PBLs level might not be an efficient biomarker for PD patients.

Highlights

  • DJ-1 has been thought as a candidate biomarker for Parkinson’s disease (PD)

  • Each group comprised 24 men and 16 women, and there was no significant difference in age (P = 0.228) between the PD patients (63.7 ± 6.16 years) and normal control (NC) (61.28 ± 9.21 years)

  • DNA Methylation of DJ-1 promoter region detected by Bisulfite specific PCR-based sequencing method Based on the NCBI database, the promoter region of human DJ-1 gene (NM_001123377) has two CpG islands (CGIs), locating at−1545 ~ −1244 bp(CpG1),−1178 ~−732 bp(CpG2)

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Summary

Introduction

DJ-1 has been thought as a candidate biomarker for Parkinson’s disease (PD) It was found reduced in PD brains, CSF and saliva, there were conflicting results. Blood-based DNA methylation represents a highly promising biomarker for PD by regulating the causative gene expression. In this study, we try to explore whether blood-based DNA methylation of DJ-1 could be used as a biomarker to differentiate PD patients from normal control (NC), and whether DNA methylation could regulate DJ-1 expression in a SH-SY5Y cell model. In sporadic PD patients, the level of total DJ-1 protein was significantly reduced in the substantia nigra (SN) and CSF [3,4,5], there were conflicting results [6]. The molecular mechanisms underlying the decreased DJ-1 level are not yet clear

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