中国汉族男性精神分裂症和甲基苯丙胺所致精神障碍患者精神症状与代谢谷氨酸受体 8 基因 CpG 甲基化增加相关的纵向研究。

IF 3 Q2 PSYCHIATRY
Huixi Dong, Tao Luo, Cheng Yang, Mengqi Liu, Yidong Shen, Wei Hao
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引用次数: 0

摘要

吸食甲基苯丙胺会产生与精神分裂症(SCZ)几乎无异的精神症状。DNA 甲基化的变异可能与精神病的病因和纵向发展密切相关。然而,精神病症状、功能障碍和 DNA 甲基化之间的关系仍不清楚。本研究包括三个阶段:发现、验证和随访。在发现阶段,我们在外周血单核细胞中采用了全基因组DNA甲基化分析(Illumina 450K),以测试DNA甲基化是否与具有代表性的SCZ和甲基苯丙胺所致精神障碍(MIP)患者的精神病症状和功能状态有关。然后,我们在 UBA6、APOL3、KIF17、MLLT3、GRM8、CSNK1E 和 SETDB1 中发现了七个不同的甲基化区域/基因(DMRs),这些区域/基因与之前精神病研究中报告的基因变异重叠。在验证阶段,我们采用 MethLight qPCR 方法对中国汉族男性(109 名 SCZ 患者,99 名甲基苯丙胺使用障碍伴 MIP 患者,150 名甲基苯丙胺使用障碍非 MIP 患者,282 名正常对照,年龄范围:18-50 岁)的上述 7 个基因进行了比较:18-50岁)。GRM8显示出强烈的甲基化改变,在随后的验证中通过了严格的过滤,表明其对SCZ和MIP有显著的贡献。此外,在基线和随访期间,GRM8的高甲基化与积极消极综合征量表和世卫组织残疾评估表II的总分有显著关联。我们的研究结果表明,在 SCZ 和 MIP 的跨诊断样本中,GRM8 启动子中 CpG 甲基化的增加是精神病症状的潜在候选表观遗传生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Psychotic symptoms associated increased CpG methylation of metabotropic glutamate receptor 8 gene in Chinese Han males with schizophrenia and methamphetamine induced psychotic disorder: a longitudinal study.

Methamphetamine use can produce psychotic symptoms almost indistinguishable from schizophrenia (SCZ). Variation in DNA methylation may be closely implicated in the etiology and longitudinal development of psychiatric disorders. However, the relationship between psychotic symptoms, functional disability, and DNA methylation is still unclear. This study consists of three periods: discovery, validation, and follow-up. In the discovery stage, we employed genome-wide DNA methylation profiling (Illumina 450K) in peripheral blood mononuclear cells to test whether DNA methylation associates with psychotic symptoms and function state in representative SCZ and methamphetamine-induced psychotic disorder (MIP) patients. Then, we found seven differentially methylated regions/genes (DMRs, in UBA6, APOL3, KIF17, MLLT3, GRM8, CSNK1E, SETDB1) overlapping with genetic variants reported in previous studies of psychosis. In the validation stage, we compared the above-mentioned seven genes by MethLight qPCR method in Chinese Han males (N = 109 SCZ patients, N = 99 methamphetamine use disorder with MIP patients, N = 150 methamphetamine use disorder without MIP patients, N = 282 normal controls, age range: 18-50 years). GRM8 showed robustly altered methylation, which has passed rigorous filtration in subsequent validation, suggesting a remarkable contribution to SCZ and MIP. In addition, hypermethylation of GRM8 showed a significant association with the total scores of the Positive Negative Syndrome Scale and WHO disability assessment schedule II in both baseline and follow-up periods. Our findings suggest that increased CpG methylation in the promoter of GRM8 is a potential candidate epigenetic biomarker of psychotic symptoms in transdiagnostic samples of SCZ and MIP.

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