α-Synuclein Gene Hypomethylation in LRRK2 Parkinson's Disease Patients

IF 7.6 1区医学 Q1 CLINICAL NEUROLOGY Movement Disorders Pub Date : 2024-12-23 DOI:10.1002/mds.30094

Lorena de Mena PhD, Guillem Parés PhD, Alicia Garrido MD, Daniel F. Pilco-Janeta MD, PhD, Manel Fernández MLT, Jesica Pérez MSc, Eduardo Tolosa MD, PhD, Ana Cámara MSc, Francesc Valldeoriola MD, PhD, Mario Ezquerra PhD, María-José Martí MD, PhD, Rubén Fernández-Santiago PhD, the Barcelona LRRK2 Study Group

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Abstract

Background

α-Synuclein (SNCA) gene hypomethylation was reported in idiopathic Parkinson's disease (iPD). Based on a high clinical resemblance between iPD and leucine-rich repeat kinase 2 (LRRK2)-driven Parkinson's disease (L2PD), we investigated the epigenetic status of SNCA in an extensive LRRK2 clinical cohort from Spain.

Methods

We assessed the methylation levels of 23 CpG sites in the SNCA promoter region using peripheral blood DNA from L2PD patients (n = 151), LRRK2 nonmanifesting carriers (n = 55), iPD patients (n = 115), and healthy control subjects (n = 154) (total: N = 475).

Results

Compared with control subjects, we found significant SNCA hypomethylation in 11 of 23 CpGs in L2PD (48%), whereas 22 CpGs (96%) were hypomethylated in iPD. In line with a healthy status, asymptomatic mutation carriers had similar SNCA methylation profiles to control subjects.

Conclusions

This study shows for the first time that SNCA hypomethylation occurs in patients with L2PD. Further studies addressing SNCA methylation status in additional worldwide LRRK2 cohorts are warranted. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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LRRK2帕金森病患者α-突触核蛋白基因低甲基化

背景：α-突触核蛋白（SNCA）基因低甲基化在特发性帕金森病（iPD）中有报道。基于iPD和富含亮氨酸重复激酶2 （LRRK2）驱动的帕金森病（L2PD）之间的高度临床相似性，我们研究了来自西班牙的LRRK2临床队列中SNCA的表观遗传状况。方法：我们使用L2PD患者（n = 151）、LRRK2非显性携带者（n = 55）、iPD患者（n = 115）和健康对照者（n = 154）（总n = 475）的外周血DNA评估SNCA启动子区域23个CpG位点的甲基化水平。结果：与对照组相比，我们发现L2PD患者的23个CpGs中有11个（48%）存在显著的SNCA低甲基化，而iPD患者的22个CpGs（96%）存在低甲基化。与健康状态一致，无症状突变携带者具有与对照受试者相似的SNCA甲基化谱。结论：本研究首次表明，SNCA低甲基化发生在L2PD患者中。需要在全球其他LRRK2队列中进一步研究SNCA甲基化状态。©2024作者。Wiley期刊有限责任公司代表国际帕金森和运动障碍学会出版的《运动障碍》。

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来源期刊

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.