Zhou Shengjun, Zhang Junjun, Zhou Chenhui, Gong Fanyong, Zhu Xueli, Pan Xingqiang, Sun Jie, Gao Xiang, Huang Yi
Department of Neurosurgery, Ningbo First Hospital, Ningbo, China.
Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province, Ningbo, China.
Front Aging Neurosci. 2022 Jul 11;14:885680. doi: 10.3389/fnagi.2022.885680. eCollection 2022.
: This study is aimed to investigate the contribution of patatin-like phospholipase domain-containing protein 6 () DNA methylation to the risk of intracranial aneurysm (IA) in the Han Chinese population. : A total of 96 age- and sex-matched participants were recruited to evaluate methylation bisulfite pyrosequencing. The mRNA expression in the plasma was determined using real-time quantitative reverse transcription-polymerase chain reaction. Human primary artery smooth muscle cells (HPCASMC) were used for the in vitro function study. : methylation was significantly higher in patients with IA than in healthy controls ( < 0.01). Sex group analysis showed that this correlation appeared in the male group ( < 0.01) but not in the female group ( > 0.05). methylation was significantly associated with age in all participants ( = 0.306, = 0.003) and in the control group ( = 0.377, = 0.008) but not in the IA group ( = 0.127, = 0.402). Furthermore, the mRNA expression significantly decreased in patients with IA than that in the controls ( = 0.016). expression was significantly inversely correlated with elevated DNA methylation in participants (r = -0.825, < 0.0001). In addition, transcription was significantly enhanced following treatment with 5-aza-2'-deoxycytidine methylation inhibitor in HPCASMC.The receiver operating characteristic analyses of curves showed that the mean methylation [area under the curve (AUC) = 0.74, < 0.001] and mRNA expression (AUC = 0.86, < 0.001) could have a diagnostic value for patients with IA. : Although future functional experiments are required to test our hypothesis, our study demonstrated that methylation and mRNA expression were significantly associated with the risk of IA; thus, they show potential for use in the early diagnosis of IA.
本研究旨在探讨含patatin样磷脂酶结构域蛋白6（）DNA甲基化对汉族人群颅内动脉瘤（IA）发病风险的影响。共招募了96名年龄和性别匹配的参与者，采用亚硫酸氢盐焦磷酸测序法评估甲基化情况。采用实时定量逆转录-聚合酶链反应测定血浆中的mRNA表达。使用人原发性动脉平滑肌细胞（HPCASMC）进行体外功能研究。IA患者的甲基化水平显著高于健康对照组（<0.01）。性别分组分析显示，这种相关性在男性组中存在（<0.01），而在女性组中不存在（>0.05）。在所有参与者中（=0.306，=0.003）以及对照组中（=0.377，=0.008），甲基化与年龄显著相关，但在IA组中不相关（=0.127，=0.402）。此外，IA患者的mRNA表达显著低于对照组（=0.016）。在参与者中，表达与DNA甲基化升高显著负相关（r=-0.825，<0.0001）。此外，在HPCASMC中用5-氮杂-2'-脱氧胞苷甲基化抑制剂处理后，转录显著增强。曲线下面积（AUC）的受试者工作特征分析表明，平均甲基化水平（AUC=0.74，<0.001）和mRNA表达（AUC=0.86，<0.001）对IA患者具有诊断价值。尽管未来需要进行功能实验来验证我们的假设，但我们的研究表明，甲基化和mRNA表达与IA风险显著相关；因此，它们在IA的早期诊断中显示出应用潜力。
