Pihlstrøm Lasse, Berge Victoria, Rengmark Aina, Toft Mathias
Department of Neurology, Oslo University Hospital, Oslo, Norway.
Mov Disord. 2015 Apr;30(4):577-80. doi: 10.1002/mds.26073. Epub 2014 Dec 27.
Genome-wide association studies have demonstrated association between SNCA variability and susceptibility to Parkinson's disease, but causal mechanisms are unclear. We hypothesized that risk variants affect methylation of a putative promoter in SNCA intron 1, previously highlighted in epigenetic studies of Parkinson's disease.
We analyzed sample sets from blood (n = 72) and cerebral cortex (n = 24) in Parkinson's disease patients and healthy controls. We genotyped SNCA single-nucleotide polymorphisms, examined messenger RNA (mRNA) expression and assessed intron 1 methylation levels by methylation-sensitive restriction enzyme digestion and quantitative polymerase chain reaction (PCR).
Patients showed significant hypomethylation as compared with controls in the blood sample set. In addition, rs3756063 was associated with SNCA methylation level in both blood (P = 5.9 × 10(-5)) and brain (P = 0.023).
Our findings support a link between SNCA variability, promoter methylation, and Parkinson's disease risk and indicate that methylation patterns in brain are mirrored in the blood. SNCA methylation warrants further investigation as a potential biomarker.
全基因组关联研究已证明α-突触核蛋白（SNCA）的变异性与帕金森病易感性之间存在关联，但因果机制尚不清楚。我们推测风险变异会影响SNCA内含子1中一个假定启动子的甲基化，该启动子在帕金森病的表观遗传学研究中曾被重点关注。
我们分析了帕金森病患者和健康对照者的血液样本集（n = 72）和大脑皮质样本集（n = 24）。我们对SNCA单核苷酸多态性进行基因分型，检测信使核糖核酸（mRNA）表达，并通过甲基化敏感限制性内切酶消化和定量聚合酶链反应（PCR）评估内含子1的甲基化水平。
与对照组相比，患者血液样本集中出现了显著的低甲基化。此外，rs3756063与血液（P = 5.9 × 10⁻⁵）和大脑（P = 0.023）中的SNCA甲基化水平均相关。
我们的研究结果支持SNCA变异性、启动子甲基化与帕金森病风险之间存在联系，并表明大脑中的甲基化模式在血液中也有体现。SNCA甲基化作为一种潜在的生物标志物值得进一步研究。
