Association of Two Polymorphisms in CCL2 With Parkinson's Disease: A Case-Control Study
Association of Two Polymorphisms in CCL2 With Parkinson's Disease: A Case-Control Study
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CCL2 的两个多态性与帕金森病的关联：病例对照研究
DOI：
10.3389/fneur.2019.00035
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发表时间：
2019-01
影响因子：
3.4
通讯作者：
Ding Jianqing
中科院分区：
文献类型：
--
作者：
Shen Ruinan;Lin Suzhen;He Lu;Zhu Xue;Zhou Zhekun;Chen Shengdi;Wang Ying;Ding Jianqing
背景：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。趋化因子通常通过上调表达水平来参与这一过程，这与其基因的多态性密切相关。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，但与中国汉族人群无关。方法：采用PCR-RFLP方法对411例PD患者和422例性别年龄匹配的中国汉族人群的CCL2启动子区进行测序。对他们的基因型频率进行统计分析。在神经母细胞瘤细胞中进行双荧光素酶报告基因测定，以评估 CCL2 中 rs1024611 变体 (T>C) 和 GRCh38.p12chr17:34252593 G>C 等位基因的启动子转录活性。结果：我们发现rs1024611的CCL2基因型频率在PD组和对照组之间存在显着差异（p=0.021），而C等位基因与PD组中的风险显着增加相关（p=0.004）。此外，CCL2 中新发现的 C 等位基因 (GRCh38.p12chr17:34252593 G>C) 也被发现与 PD 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，rs1024611 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。结论：我们首次报告了 CCL2 上的一个风险多态性 (rs1024611) 和一个新基因座 (GRCh38.p12chr17:.34252593 G>C)，这两者都被认为是中国汉族人群中 PD 的危险因素。
Background: 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. Methods: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. Results:We found that the frequency of the CCL2 genotype of rs1024611 was significantly different between the PD and control groups (p = 0.021), while the C allele was associated with a significantly increased risk in the PD group (p = 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. Conclusions: 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.
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DOI：
10.1007/978-3-319-77525-8_100075
发表时间：
2018-12
期刊：
Encyclopedia of Big Data Technologies
影响因子：
--
作者：
通讯作者：
--
影响因子：
3
作者：
通讯作者：
--
DOI：
10.1210/jcem.85.1.6229
发表时间：
2000
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1109/icmas.2000.858517
发表时间：
2000-07
期刊：
Proceedings Fourth International Conference on MultiAgent Systems
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.4
作者：
Jones OD;Schall JD;Shen FX
通讯作者：
Shen FX