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儿童和青少年中氟西汀反应的DNA甲基化:初步结果

DNA Methylation of Fluoxetine Response in Child and Adolescence: Preliminary Results.

作者信息

Martinez-Pinteño Albert, Rodriguez Natalia, Blázquez Ana, Plana Maria Teresa, Varela Eva, Gassó Patricia, Lafuente Amalia, Lazaro Luisa, Mas Sergi

机构信息

Department of Basic Clinal Practice, Pharmacology Unit, University of Barcelona, Barcelona, Spain.

Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clinic de Barcelona, Barcelona, Spain.

出版信息

Pharmgenomics Pers Med. 2021 Apr 19;14:459-467. doi: 10.2147/PGPM.S289480. eCollection 2021.

Abstract

PURPOSE

The search for predictors of antidepressant response is gaining increasing attention, with epigenetic markers attracting a great deal of interest. We performed a genome-wide study assessing baseline differences in DNA methylation between Responders and Non-Responders.

PATIENTS AND METHODS

Twenty-two children and adolescents, receiving fluoxetine treatment for the first time, were classified as Responders or Non-Responders according to CGI-I score after 8 weeks of fluoxetine treatment. Genome-wide DNA methylation was profiled using the Illumina Infinium MethylationEPIC BeadChip Kit and analyzed using the Chip Analysis Methylation Pipeline (ChAMP).

RESULTS

We identified 21 CpG sites significantly (FDR<0.05) associated with fluoxetine response that showed meaningful differences (Δβ> ±0.2) in methylation level between Responders and Non-Responders. Two genes, () and , presented more than one significant CpG sites.

CONCLUSION

Our findings provide new insights into the molecular mechanisms underlying the complex phenotype of antidepressant response, indicating that methylation at specific genes could be a promising biomarker that needs further replication in large cohorts.

摘要

目的

寻找抗抑郁反应的预测指标日益受到关注,表观遗传标记引发了大量兴趣。我们进行了一项全基因组研究,评估反应者与无反应者之间DNA甲基化的基线差异。

患者与方法

22名首次接受氟西汀治疗的儿童和青少年,根据氟西汀治疗8周后的CGI-I评分分为反应者或无反应者。使用Illumina Infinium MethylationEPIC BeadChip试剂盒对全基因组DNA甲基化进行分析,并使用芯片分析甲基化管道(ChAMP)进行分析。

结果

我们鉴定出21个与氟西汀反应显著相关(FDR<0.05)的CpG位点,这些位点在反应者与无反应者之间的甲基化水平显示出有意义的差异(Δβ>±0.2)。两个基因,()和,呈现出不止一个显著的CpG位点。

结论

我们的研究结果为抗抑郁反应复杂表型背后的分子机制提供了新的见解,表明特定基因的甲基化可能是一种有前途的生物标志物,需要在大型队列中进一步验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31ad/8064712/2a3426b7250d/PGPM-14-459-g0001.jpg

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