Lin S, He L, Shen R, Fang F, Pan H, Zhu X, Wang M, Zhou Z, Liu Z, Wang X, Fang S, Sun X, Wang Y, Chen S, Ding J
Institute of Neurology and Department of Neurology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Department of Aging, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Eur J Neurol. 2020 Jul;27(7):1224-1230. doi: 10.1111/ene.14224. Epub 2020 Apr 14.
Neuroinflammation is known to be involved in the pathogenesis of Parkinson's disease (PD). Abnormal activation of microglia plays a key role in this pathological process. CD200R1 is a membrane glycoprotein that is expressed primarily on myeloid cells including microglia and is involved in the maintenance of microglia in a stationary state. Our previous study reported that the regulation of CD200R1 expression is altered in PD patients. Such alteration will lead to neuroinflammation and is related to the pathogenesis of PD. The possible role of promoter polymorphisms for abnormal CD200R1 expression in PD was examined in this study.
The UCSC database and dual-luciferase assays were used to confirm the promoter region of CD200R1. The promoter of CD200R1 was sequenced in 457 PD patients and 520 matched healthy controls from the Chinese Han population. Dual-luciferase assays were conducted to examine the promoter activity of CD200R1.
It was confirmed that the promoter of CD200R1 is located in the region 876-146 bp upstream of the coding DNA sequence. The frequencies of rs144721913 (P = 0.001) and rs72952157 (P = 0.022) in the promoter were significantly different between the PD group and control group. rs144721913 increases the risk of PD by approximately 14-fold and rs72952157 by 2.6-fold. The dual-luciferase assay indicated that the rs144721913 T allele and the rs72952157 G allele reduced the transcriptional activity of the CD200R1 promoter.
For the first time the promoter region of CD200R1 has been defined and two potential risk polymorphisms (rs144721913 and rs72952157) in the region for PD in Chinese Han populations have been reported.
已知神经炎症参与帕金森病（PD）的发病机制。小胶质细胞的异常激活在这一病理过程中起关键作用。CD200R1是一种膜糖蛋白，主要表达于包括小胶质细胞在内的髓样细胞上，参与维持小胶质细胞的静止状态。我们之前的研究报道，PD患者中CD200R1表达的调控发生改变。这种改变会导致神经炎症，且与PD的发病机制相关。本研究检测了启动子多态性在PD患者CD200R1异常表达中的可能作用。
使用UCSC数据库和双荧光素酶测定法来确认CD200R1的启动子区域。对457例PD患者和520例来自中国汉族人群的匹配健康对照者的CD200R1启动子进行测序。进行双荧光素酶测定以检测CD200R1的启动子活性。
证实CD200R1的启动子位于编码DNA序列上游876 - 146 bp区域。启动子中rs144721913（P = 0.001）和rs72952157（P = 0.022）在PD组和对照组之间的频率存在显著差异。rs144721913使PD风险增加约14倍，rs72952157使PD风险增加2.6倍。双荧光素酶测定表明，rs144721913的T等位基因和rs72952157的G等位基因降低了CD200R1启动子的转录活性。
首次明确了CD200R1的启动子区域，并报道了中国汉族人群中该区域两个潜在的PD风险多态性（rs144721913和rs72952157）。
