Identification of the CD200R1 promoter and the association of its polymorphisms with the risk of Parkinson's disease
Identification of the CD200R1 promoter and the association of its polymorphisms with the risk of Parkinson's disease
复制标题
CD200R1 启动子的鉴定及其多态性与帕金森病风险的关联
DOI：
10.1111/ene.14224
复制
发表时间：
2020-04-14
影响因子：
5.1
通讯作者：
Ding, J.
中科院分区：
文献类型：
--
作者：
Lin, S.;He, L.;Ding, J.
背景与目的帕金森病（Parkinson 'sdisease，PD）的发病机制中存在神经炎症反应。小胶质细胞的异常激活在这一病理过程中起着关键作用。CD 200 R1是一种膜糖蛋白，主要在包括小胶质细胞在内的骨髓细胞上表达，并参与维持小胶质细胞处于静止状态。我们以前的研究报告，CD 200 R1表达的调节在PD患者中改变。这种改变将导致神经炎症，并与PD的发病机制有关。方法应用UCSC数据库和双荧光素酶分析法对CD 200 R1基因启动子区进行确认。对457例PD患者和520例健康对照者的CD 200 R1基因启动子进行测序。结果CD 200 R1基因启动子位于编码区上游876-146 bp，启动子区的大小与CD 200 R1基因的启动子序列一致。在PD组和对照组中，启动子区rs 144721913（P = 0.001）和rs72952157（P = 0.022）的频率差异有统计学意义。rs 144721913使PD风险增加约14倍，rs72952157增加2.6倍。双荧光素酶检测结果表明，rs 144721913 T等位基因和rs72952157 G等位基因降低了CD 200 R1启动子的转录活性。在中国汉族人群中，已报告了该地区的PD（rs 144721913和rs72952157）。
Background and purpose 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.Method 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.Results 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.Conclusions 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.