Methylation of 伪-synuclein and leucine-rich repeat kinase 2 in leukocyte DNA of Parkinson's disease patients

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• 作者：Yu-yan Tan¹ ; ^{rabbit82@gmail.com" class="auth_mail} ; Li Wu¹ ; ^{breezy51@163.com" class="auth_mail} ; Zong-bo Zhao ^{san_pi_love@126.com" class="auth_mail} ; Ying Wang ^{wang-ying@medmail.com.cn" class="auth_mail} ; Qin Xiao ^{xiaoqin67@medmail.com.cn" class="auth_mail} ; Jun Liu ^{jly0520@hotmail.com" class="auth_mail} ; Gang Wang ^{wgneuron@hotmail.com" class="auth_mail} ; Jian-fang Ma ^{mjf74@163.com" class="auth_mail} ; Sheng-di Chen ; ^{chen_sd@medmail.com.cn" class="auth_mail}
• 关键词：Parkinson's disease ; DNA methylation ; SNCA ; LRRK2
• 刊名：Parkinsonism and Related Disorders
• 出版年：March, 2014
• 年：2014
• 卷：20
• 期：3
• 页码：308-313
• 全文大小：1305 K

文摘

Background

Recent studies highlight the role of DNA methylation in the pathogenesis of Parkinson's disease (PD). However, there is a paucity of studies exploring the role of blood-based DNA methylation in PD. We aimed to explore identifiable epigenetic biomarkers for PD by analyzing the methylation status of 伪-synuclein (SNCA) and leucine-rich repeat kinase 2 (LRRK2) in leukocytes.

Methods

Bisulfite Specific PCR-based Sequencing method was used for semi-quantitative detection of methylation status of CpG islands in SNCA and LRRK2 promoter regions. Bisulfite Specific Cloning-based Sequencing method was used for further quantitative examination of CpG-2 methylation of SNCA. mRNA level was also detected in leukocytes.

Results

Semi-quantitative detection showed that the methylation status of SNCA CpG-2 differed between PD patients and normal controls, while there was no difference in CpG-1 of SNCA or in LRRK2 promoter. Further quantitative analysis by clonal assay showed that the CpG-2 of SNCA was hypomethylated in PD patients compared with the normal control (5.90% versus 7.69%, P = 0.034). Moreover, among the 14 CpG sites of CpG-2, the 2nd, 4th and 9th CpG sites were significantly hypomethylated in PD patients. In subgroups of PD, the methylation level decreased in the early-onset PD patients (P = 0.001). RT-PCR examination showed that SNCA mRNA was increased in PD patients compared with normal control (P = 0.003).

Conclusions

Our results indicated that the methylation level of SNCA CpG-2, especially that of the 2nd, 4th and 9th CpG sites in leukocytes might have great potential to be a useful and informative biomarker in PD diagnosis and treatment.