Song Jiaqi, Chen Yan, Zhao Qing, Li Hongna, Li Wei, Chen Ke, Yu Jianjin, Fu Weihong, Chen Dachun
Huilongguan Clinical Medical School, Beijing Huilongguan Hospital, Peking University, Beijing, China.
Beijing HuiLongGuan Hospital, Beijing, China.
Front Psychiatry. 2022 Feb 7;13:793910. doi: 10.3389/fpsyt.2022.793910. eCollection 2022.
Leptin involved in the regulation of dopaminergic neurons of the central nervous system may confirm the hypothesis of neurodevelopment in schizophrenic patients. However, specific genetic mechanisms are undefined. Therefore, we aimed to explore the regulation of DNA methylation of leptin promoters and mRNA expression in patients with schizophrenia. A cross-sectional study enrolled 40 patients and 40 healthy controls from the Beijing Huilongguan Hospital in China. The leptin methylation levels and mRNA expression were examined by highly sensitive mass spectrometry based on the MassARRAY System and real-time quantitative polymerase chain reaction (qPCR). The Positive and Negative Symptoms Scale (PANSS) was applied to estimate the clinical symptoms of patients. The -CpG7 and CpG15 methylation in patients were significantly higher than in healthy controls ( < 0.05). The -CpG11, CpG33.34.35, CpG36 methylation, and mRNA expression decreased significantly in patients compared with healthy controls ( < 0.05). After controlling gender, age, BMI, dose of antipsychotic and duration of illness, -CpG7 methylation was negatively associated with PANSS positive symptoms subscore ( = -0.485, = 0.005). In addition, -mRNA expression was negatively correlated with PANSS total score ( = -0.385, = 0.03) and positive subscale ( = -0.392, = 0.026). Nevertheless, only the -CpG7 methylation level remained negatively correlated to the PANSS positive subscore following multiple stepwise regression (β = -17.071, = 0.037). These results suggest that leptin methylation and mRNA expression might contribute to the pathogenesis of schizophrenia. -CpG7 methylation may be negatively associated with positive symptoms in patients with schizophrenia.
瘦素参与中枢神经系统多巴胺能神经元的调节，这可能证实了精神分裂症患者神经发育的假说。然而，具体的遗传机制尚不清楚。因此，我们旨在探讨精神分裂症患者中瘦素启动子的DNA甲基化调控及mRNA表达。一项横断面研究纳入了来自中国北京回龙观医院的40例患者和40名健康对照。基于MassARRAY系统的高灵敏度质谱法和实时定量聚合酶链反应（qPCR）检测瘦素甲基化水平和mRNA表达。采用阳性和阴性症状量表（PANSS）评估患者的临床症状。患者中-CpG7和CpG15甲基化显著高于健康对照（<0.05）。与健康对照相比，患者中-CpG11、CpG33.34.35、CpG36甲基化及mRNA表达显著降低（<0.05）。在控制性别、年龄、BMI、抗精神病药物剂量和病程后，-CpG7甲基化与PANSS阳性症状亚评分呈负相关（=-0.485，=0.005）。此外，-mRNA表达与PANSS总分（=-0.385，=0.03）和阳性亚量表（=-0.392，=0.026）呈负相关。然而，经过多重逐步回归后，只有-CpG7甲基化水平与PANSS阳性亚评分仍呈负相关（β=-17.071，=0.037）。这些结果表明，瘦素甲基化和mRNA表达可能参与精神分裂症的发病机制。-CpG7甲基化可能与精神分裂症患者的阳性症状呈负相关。
