Epigenetic approach to early-onset Parkinson's disease: low methylation status of SNCA and PARK2 promoter regions

被引：31

作者：

Eryilmaz, Isil Ezgi ^{[1
]}

Cecener, Gulsah ^{[1
]}

Erer, Sevda ^{[2
]}

Egeli, Unal ^{[1
]}

Tunca, Berrin ^{[1
]}

Zarifoglu, Mehmet ^{[1
]}

Elibol, Bulent ^{[3
]}

Tokcaer, Ayse Bora ^{[4
]}

Saka, Esen ^{[3
]}

Demirkiran, Meltem ^{[5
]}

Akbostanci, Cenk ^{[6
]}

Dogu, Okan ^{[7
]}

Colakoglu, Beril ^{[8
]}

Kenangil, Gulay ^{[9
]}

Kaleagasi, Hakan ^{[7
]}

机构：

[1] Uludag Univ, Dept Med Biol, Fac Med, Bursa, Turkey

[2] Uludag Univ, Dept Neurol, Fac Med, Bursa, Turkey

[3] Hacettepe Univ, Dept Neurol, Fac Med, Ankara, Turkey

[4] Gazi Univ, Dept Neurol, Fac Med, Ankara, Turkey

[5] Cukurova Univ, Dept Neurol, Fac Med, Adana, Turkey

[6] Ankara Univ, Dept Neurol, Fac Med, Ankara, Turkey

[7] Mersin Univ, Dept Neurol, Fac Med, Mersin, Turkey

[8] Dokuz Eylul Univ, Dept Neurol, Fac Med, Izmir, Turkey

[9] Erenkoy Training & Res Hosp Neurol & Psychiat Dis, Istanbul, Turkey

来源：

NEUROLOGICAL RESEARCH | 2017年 / 39卷 / 11期

关键词：

Early-onset Parkinson's disease; epigenetic; methylation; SNCA; PARK2; ALPHA-SYNUCLEIN; LEUKOCYTE DNA; GENE; MUTATIONS; EXPRESSION;

D O I：

10.1080/01616412.2017.1368141

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background and aim: The effect of epigenetic modifications in the genes related to Parkinson's disease (PD) is still unclear. In the present study, we investigated methylation status of SNCA and PARK2 genes in patients with early-onset Parkinson's disease (EOPD). Materials and methods: The promoter region methylation status of SNCA and PARK2 genes was evaluated by methylation specific-PCR (MSP) in 91 patients with EOPD and 52 healthy individuals. Results: The methylation of SNCA and PARK2 promoter regions were significantly lower in EOPD patients compared to the control group (P = 0.013 and P = 0.03, respectively). We also found that the methylation status of the SNCA might be associated with positive family history of PD (P = 0.042). Conclusion: Although it should be supported by further analysis, based on the results of the present study, the methylation status of SNCA and PARK2 genes might contribute to EOPD pathogenesis.

引用

页码：965 / 972

页数：8

共 32 条

[1] Abnormal methylation of the common PARK2 and PACRG promoter is associated with downregulation of gene expression in acute lymphoblastic leukemia and chronic myeloid leukemia [J].

Agirre, X ;

Román-Gómez, J ;

Vázquez, I ;

Jiménez-Velasco, A ;

Garate, L ;

Montiel-Duarte, C ;

Artieda, P ;

Cordeu, L ;

Lahortiga, I ;

Calasanz, MJ ;

Heiniger, A ;

Torres, A ;

Minna, JD ;

Prósper, F .

INTERNATIONAL JOURNAL OF CANCER, 2006, 118 (08) :1945-1953

[2] Hypomethylation of SNCA in blood of patients with sporadic Parkinson's disease [J].

Ai, San-xi ;

Xu, Qian ;

Hu, Ya-cen ;

Song, Cheng-yuan ;

Guo, Ji-feng ;

Shen, Lu ;

Wang, Chun-rong ;

Yu, Ri-li ;

Yan, Xin-xiang ;

Tang, Bei-sha .

JOURNAL OF THE NEUROLOGICAL SCIENCES, 2014, 337 (1-2) :123-128

[3] Study of Methylation Levels of Parkin Gene Promoter in Parkinson's Disease Patients [J].

Cai, Miao ;

Tian, Jun ;

Zhao, Guo-hua ;

Luo, Wei ;

Zhang, Bao-rong .

INTERNATIONAL JOURNAL OF NEUROSCIENCE, 2011, 121 (09) :497-502

[4] Parkin, a gene implicated in autosomal recessive juvenile parkinsonism, is a candidate tumor suppressor gene on chromosome 6q25-q27 (Publication with Expression of Concern. See vol. 114, 2017) [J].

Cesari, R ;

Martin, ES ;

Calin, GA ;

Pentimalli, F ;

Bichi, R ;

McAdams, H ;

Trapasso, F ;

Drusco, A ;

Shimizu, M ;

Mascillo, V ;

d'Andrilli, G ;

Scambia, G ;

Picchio, MC ;

Alder, H ;

Godwin, AK ;

Croce, CM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (10) :5956-5961

[5] Mitochondrial dynamics-fusion, fission, movement, and mitophagy-in neurodegenerative diseases [J].

Chen, Hsiuchen ;

Chan, David C. .

HUMAN MOLECULAR GENETICS, 2009, 18 :R169-R176

[6] Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin [J].

Clark, Ira E. ;

Dodson, Mark W. ;

Jiang, Changan ;

Cao, Joseph H. ;

Huh, Jun R. ;

Seol, Jae Hong ;

Yoo, Soon Ji ;

Hay, Bruce A. ;

Guo, Ming .

NATURE, 2006, 441 (7097) :1162-1166

[7] Next-Generation Sequencing Reveals Regional Differences of the α-Synuclein Methylation State Independent of Lewy Body Disease [J].

de Boni, L. ;

Tierling, S. ;

Roeber, S. ;

Walter, J. ;

Giese, A. ;

Kretzschmar, Hans A. .

NEUROMOLECULAR MEDICINE, 2011, 13 (04) :310-320

[8] Epidemiology of Parkinson's disease [J].

de Lau, Lonneke M. L. ;

Breteler, Monique M. B. .

LANCET NEUROLOGY, 2006, 5 (06) :525-535

[9] No Differential DNA Methylation of PARK2 in Brain of Parkinson's Disease Patients and Healthy Controls [J].

De Mena, Lorena ;

Cardo, Lucia F. ;

Coto, Eliecer ;

Alvarez, Victoria .

MOVEMENT DISORDERS, 2013, 28 (14) :2032-2033

[10] Alterations in the common fragile site gene Parkin in ovarian and other cancers [J].

Denison, SR ;

Wang, F ;

Becker, NA ;

Schüle, B ;

Kock, N ;

Phillips, LA ;

Klein, C ;

Smith, DI .

ONCOGENE, 2003, 22 (51) :8370-8378

← 1 2 3 4 →