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脑源性神经营养因子外显子 I 区甲基化在舍曲林治疗抑郁症中的作用及其临床诊断价值。

The role of BDNF exon I region methylation in the treatment of depression with sertraline and its clinical diagnostic value.

机构信息

Department of Affective Disorder, Ningbo Kangning Hospital, Ningbo, Zhejiang, China.

School of Medicine, Ningbo University, Ningbo, Zhejiang, China.

出版信息

J Clin Lab Anal. 2021 Nov;35(11):e23993. doi: 10.1002/jcla.23993. Epub 2021 Sep 15.

DOI:10.1002/jcla.23993
PMID:34528295
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8605126/
Abstract

BACKGROUND

Brain-derived neurotrophic factor (BDNF) is considered to be one of the best candidate genes for depression. However, whether sertraline treatment affects the methylation level of this gene remains unknown.

METHODS

Fifty-three patients with depression and 51 healthy controls were included in the study. The methylation level of BDNF exon I was determined in blood samples from these subjects. The Hamilton Depression Scale was used to evaluate the depression status of patients. Single nucleotide polymorphism detection was used for genotyping, and a receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the methylation level of this locus in patients with depression.

RESULTS

There was a significant difference in the methylation level of BDNF exon I between the control and depression groups. No effect of sertraline monotherapy on BDNF methylation was found in subjects with depression. Moreover, no interaction was found between BDNF genotype and the per cent methylation of BDNF exon I. However, methylation at this site was positively correlated with diurnal variation and retardation scores. Blood homocysteine concentrations were significantly reduced by sertraline treatment. No influence of genotype on serum BDNF concentration was found in subjects with depression. The ROC curve showed that methylation of BDNF exon I may be used to distinguish patients from healthy people, to a certain extent.

CONCLUSION

Methylation of BDNF exon I may be used as a biomarker of depression and may be a therapeutic target for previously untreated depression.

摘要

背景

脑源性神经营养因子(BDNF)被认为是抑郁症的最佳候选基因之一。然而,舍曲林治疗是否会影响该基因的甲基化水平尚不清楚。

方法

本研究纳入了 53 名抑郁症患者和 51 名健康对照者。检测了这些受试者血液样本中 BDNF 外显子 I 的甲基化水平。采用汉密尔顿抑郁量表评估患者的抑郁状况。采用单核苷酸多态性检测进行基因分型,并采用受试者工作特征(ROC)曲线评估该基因座甲基化水平对抑郁症患者的预测价值。

结果

对照组和抑郁症组之间 BDNF 外显子 I 的甲基化水平存在显著差异。在抑郁症患者中,舍曲林单药治疗对 BDNF 甲基化没有影响。此外,BDNF 基因型与 BDNF 外显子 I 甲基化的百分比之间没有交互作用。然而,该位点的甲基化与昼间变化和迟滞评分呈正相关。舍曲林治疗可显著降低血液同型半胱氨酸浓度。在抑郁症患者中,基因型对血清 BDNF 浓度没有影响。ROC 曲线表明,BDNF 外显子 I 的甲基化程度可在一定程度上用于区分患者和健康人。

结论

BDNF 外显子 I 的甲基化可作为抑郁症的生物标志物,也可能是未经治疗的抑郁症的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05de/8605126/e4dc8040887e/JCLA-35-e23993-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05de/8605126/d7256ea6d829/JCLA-35-e23993-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05de/8605126/e4dc8040887e/JCLA-35-e23993-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05de/8605126/d7256ea6d829/JCLA-35-e23993-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05de/8605126/972d9418d6b4/JCLA-35-e23993-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05de/8605126/1e9fa8b513dd/JCLA-35-e23993-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05de/8605126/84be34a7e5d9/JCLA-35-e23993-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05de/8605126/e4dc8040887e/JCLA-35-e23993-g006.jpg

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