有自杀意念的儿童青少年双相障碍抑郁发作患者SLC6A4 基因甲基化研究
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新疆维吾尔自治区自然科学基金面上项目(2022D01C609);天山雪松计划(2020XS15);天山创新团队 (2022D14011);新疆维吾尔自治区人民医院院内项目 (20190306)


Methylation of SLC6A4 gene in bipolar depression children and adolescents with suicidal ideation
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    摘要:

    目的 探讨儿童青少年双相障碍(PBD)抑郁发作患者自杀意念与SLC6A4基因甲基化 的关系。方法 选取 2020 年 12 月至 2022 年 12 月于新疆维吾尔自治区人民医院临床心理科住院的 43 例 PBD 抑郁发作患者为研究对象。采用自杀意念自评量表(SIOSS)评估患者的自杀意念,将总分≥ 12 分且掩饰因子得分< 4 分的患者纳入有自杀意念组(n=29),将总分< 12 分的患者纳入无自杀意念组 (n=14)。采用 Methprimer 软件对SLC6A4基因启动子区进行甲基化岛预测和甲基化引物设计,将提取好 的DNA经亚硫酸盐转化后进行PCR扩增和焦磷酸盐测序,确定甲基化的CpG位点和甲基化率。比较两组 患者SLC6A4基因不同位点甲基化的差异,采用 Spearman 相关分析基因甲基化与自杀意念的相关性。 结果 基因甲基化检测结果显示,两组患者SLC6A4基因甲基化的位点包括 CpG1、CpG2.3、CpG4、 CpG5.6位点。有自杀意念组与无自杀意念组患者CpG1、CpG2.3、CpG4位点的基因甲基化率比较[48.28% (14/29)比 8/14、96.55%(28/29)比 14/14、20.69%(6/29)比 6/14],差异无统计学意义(χ2 =0.297、0.494、2.306; P> 0.05)。有自杀意念组患者的 CpG5.6 位点基因甲基化率高于无自杀意念组[68.97%(20/29)比 5/14], 差异有统计学意义(χ2 =4.289,P< 0.05)。相关分析结果显示,PBD 抑郁发作患者的 SIOSS 得分与 SLC6A4基因甲基化CpG1位点、CpG2.3位点、CpG4位点不存在相关性(r=-0.244、-0.210、-0.281;P>0.05); 与甲基化 CpG5.6 位点呈正相关(r=0.312,P< 0.05)。结论 PBD 抑郁发作患者的自杀意念与SLC6A4基 因甲基化 CpG5.6 位点有关,为明确其自杀意念的发生原因提供了基础。

    Abstract:

    Objective To explore the relationship between suicidal ideation and SLC6A4 gene methylation in children and adolescents with pediatric bipolar disorder (PBD) and depressive episodes. Methods From December 2020 to December 2022, 43 patients with PBD and depressive episodes in the Department of Clinical Psychology of Xinjiang Uygur Autonomous Region People's Hospital were selected as the research subject. The suicidal ideation of patients was evaluated using the Self-rating Idea of Suicide Scale (SIOSS). Patients with a total score of ≥ 12 and a concealment factor score of < 4 were included in the suicidal ideation group (n=29), and patients with a total score of < 12 were included in the non-suicidal ideation group (n=14). Methprimer software was used to predict methylation islands and design methylation primers in the SLC6A4 gene promoter region. The extracted DNA was transformed by sulfite for PCR amplification and pyrophosphate sequencing to determine the methylation CpG site and methylation rate. This study compared the differences in methylation at different sites of the SLC6A4 gene between two groups of patients, and adopted Spearman correlation to analyze the correlation between gene methylation and suicidal ideation. Results Gene methylation testing showed that the methylation sites of the SLC6A4 gene in both groups of patients included CpG1, CpG2.3, CpG4, and CpG5.6 sites. Comparison of gene methylation rates at CpG1, CpG2.3, and CpG4 sites in patients in the suicidal ideation group and the non-suicidal ideation group [48.28% (14/29) vs 8/14, 96.55% (28/29) vs 14/14, 20.69% (6/29) vs 6/14] , the differences were not statistically significant (χ2 =0.297, 0.494, 2.306; P > 0.05) . The rate of gene methylation at the CpG5.6 site was higher in patients in in the suicidal ideation group than in the non-suicidal ideation group [68.97% (20/29) vs 5/14] , and the difference was statistically significant (χ2 =4.289, P < 0.05). Correlation analysis showed that suicidal ideation in patients with PBD and depressive episodes was not correlated with CpG1, CpG2.3, or CpG4 site methylation in the SLC6A4 gene (r=-0.244, -0.210, -0.281; P > 0.05), but was positively correlated with CpG5.6 site methylation, and the difference was statistically significant (r=0.312, P< 0.05). Conclusions The suicidal ideation of patients with PBD and depressive episodes is related to the SLC6A4 gene methylation at CpG5.6 site, providing a basis for clarifying the causes of suicidal ideation.

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沈小琴,王丞基,阿丽米热·阿里木江,邹韶红.有自杀意念的儿童青少年双相障碍抑郁发作患者SLC6A4 基因甲基化研究[J].神经疾病与精神卫生,2023,23(11):
DOI :10.3969/j. issn.1009-6574.2023.11.003.

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  • 在线发布日期: 2023-12-26