Zhou Shengjun, Gao Xiang, Sun Jie, Lin Zhiqing, Huang Yi
Department of Neurosurgery, Ningbo First Hospital, Ningbo Hospital of Zhejiang University , Ningbo, China .
DNA Cell Biol. 2017 Jun;36(6):436-442. doi: 10.1089/dna.2016.3499. Epub 2017 Mar 27.
The aim of this study was to determine the role of DNA methylation of the platelet-derived growth factor-D (PDGFD) gene promoter in the development of intracranial aneurysms (IAs) and brain arteriovenous malformations (BAVMs). A total of 70 patients with IAs or BAVMs and 26 control individuals were enrolled for this study. The PDGFD level in the plasma was determined using enzyme-linked immunosorbent assay. DNA methylation levels of seven cytosine-phosphate-guanine (CpG) dinucleotides present in the PDGFD gene promoter were measured using bisulfite pyrosequencing technology. The plasma PDGFD levels in IA and BAVM were significantly lower than those in the control group (p = 0.0008 and 0.002, respectively). CpG1 methylation levels of the PDGFD gene promoter were significantly higher in IA patients (4.63 ± 0.35, p = 0.017) than in the control group (3.36 ± 0.35). CpG1 methylation of the PDGFD gene promoter in BAVM patients (6.00 ± 0.86, p = 0.003) was also significantly higher than that in the control group, although these differences were seen in both male and female patients (p = 2.81E-04 and p = 0.017, respectively). In addition, CpG1 methylation of the PDGFD promoter was associated with apolipoprotein E (APOE) levels in IA patients (p = 0.013). In conclusion, our study has demonstrated significant correlations between DNA methylation of the PDGFD gene promoter and the risk of developing either IA or BAVM. Furthermore, PDGFD gene promoter CpG1 methylation shows a significant correlation with APOE in IAs. Further functional studies on these relationships and correlations are warranted.
本研究的目的是确定血小板衍生生长因子-D（PDGFD）基因启动子的DNA甲基化在颅内动脉瘤（IA）和脑动静脉畸形（BAVM）发生发展中的作用。本研究共纳入70例IA或BAVM患者及26名对照个体。采用酶联免疫吸附测定法测定血浆中PDGFD水平。使用亚硫酸氢盐焦磷酸测序技术测量PDGFD基因启动子中存在的7个胞嘧啶-磷酸-鸟嘌呤（CpG）二核苷酸的DNA甲基化水平。IA和BAVM患者的血浆PDGFD水平显著低于对照组（分别为p = 0.0008和0.002）。IA患者中PDGFD基因启动子的CpG1甲基化水平（4.63±0.35，p = 0.017）显著高于对照组（3.36±0.35）。BAVM患者中PDGFD基因启动子的CpG1甲基化水平（6.00±0.86，p = 0.003）也显著高于对照组，尽管在男性和女性患者中均观察到这些差异（分别为p = 2.81E-04和p = 0.017）。此外，IA患者中PDGFD启动子的CpG1甲基化与载脂蛋白E（APOE）水平相关（p = 0.013）。总之，我们的研究表明PDGFD基因启动子的DNA甲基化与发生IA或BAVM的风险之间存在显著相关性。此外，IA中PDGFD基因启动子CpG1甲基化与APOE显著相关。有必要对这些关系和相关性进行进一步的功能研究。
