Shen Ruinan, Lin Suzhen, He Lu, Zhu Xue, Zhou Zhekun, Chen Shengdi, Wang Ying, Ding Jianqing
Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Jiaotong University School of Medicine, Shanghai, China.
Front Neurol. 2019 Jan 29;10:35. doi: 10.3389/fneur.2019.00035. eCollection 2019.
Parkinson's disease (PD) is the most common neurodegenerative movement disorder that is known to be related to neuro-inflammation. Chemokines participate in this process usually through upregulation of expression levels, which are closely related to the polymorphisms in their genes. Recent studies have further revealed the association between these polymorphisms and the risk of PD in multiple populations, but not the Chinese Han population. The promoter region of CCL2 was sequenced in 411 PD patients and 422 gender-age matched control from a Chinese Han population using PCR-RFLP method. Their genotype frequencies were analyzed statistically. Dual-luciferase reporter assays were conducted in neuroblastoma cells to assess the promoter transcriptional activity of the rs1024611 variants (T>C) and the GRCh38.p12chr17:34252593 G>C alleles in CCL2. We found that the frequency of the CCL2 genotype of rs1024611 was significantly different between the PD and control groups ( = 0.021), while the C allele was associated with a significantly increased risk in the PD group ( = 0.004). Moreover, C allele of this newly identified alteration in CCL2 (GRCh38.p12chr17:34252593 G>C) was also found to be associated with an increased risk of PD (P genotype = 0.006, P allele = 0.006). Dual-luciferase reporter assay results indicated that rs1024611 C allele and GRCh38.p12chr17:.34252593 C allele increased the transcriptional activity of the CCL2 promoter. We, for the first time, report a risk polymorphism (rs1024611) and a new locus (GRCh38.p12chr17:.34252593 G>C) on CCL2, both of which are suggested as risk factors for PD in a Chinese Han population.
帕金森病（PD）是最常见的神经退行性运动障碍，已知与神经炎症有关。趋化因子通常通过表达水平的上调参与这一过程，而表达水平与它们基因中的多态性密切相关。最近的研究进一步揭示了这些多态性与多个人群中帕金森病风险之间的关联，但未涉及中国汉族人群。采用PCR-RFLP方法对411例中国汉族帕金森病患者和422例性别年龄匹配的对照者的CCL2启动子区域进行测序。对其基因型频率进行统计学分析。在神经母细胞瘤细胞中进行双荧光素酶报告基因检测，以评估CCL2中rs1024611变异（T>C）和GRCh38.p12chr17:34252593 G>C等位基因的启动子转录活性。我们发现，rs1024611的CCL2基因型频率在帕金森病组和对照组之间存在显著差异（P = 0.021），而C等位基因与帕金森病组风险显著增加相关（P = 0.004）。此外，还发现CCL2中这个新鉴定的改变（GRCh38.p12chr17:34252593 G>C）的C等位基因也与帕金森病风险增加相关（P基因型 = 0.006，P等位基因 = 0.006）。双荧光素酶报告基因检测结果表明，rslo24611 C等位基因和GRCh38.p12chr17:.34252593 C等位基因增加了CCL2启动子的转录活性。我们首次报道了CCL2上的一个风险多态性（rs1024611）和一个新位点（GRCh38.p12chr17:.34252593 G>C），两者均被认为是中国汉族人群中帕金森病的风险因素。
