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基于加权基因共表达网络分析的别嘌醇诱导的严重皮肤不良反应的DNA甲基化谱分析：一种药物超敏反应易感性的DNA甲基化特征

WGCNA-Based DNA Methylation Profiling Analysis on Allopurinol-Induced Severe Cutaneous Adverse Reactions: A DNA Methylation Signature for Predisposing Drug Hypersensitivity.

作者信息

Cheng Lin, Sun Bao, Xiong Yan, Hu Lei, Gao Lichen, Li Ji, Xie Hongfu, Chen Xiaoping, Zhang Wei, Zhou Hong-Hao

机构信息

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.

School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China.

出版信息

J Pers Med. 2022 Mar 24;12(4):525. doi: 10.3390/jpm12040525.

DOI:10.3390/jpm12040525
PMID:35455641
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9027774/
Abstract

BACKGROUND

The role of aberrant DNA methylation in allopurinol-induced severe cutaneous adverse reactions (SCARs) is incompletely understood. To fill the gap, we analyze the DNA methylation profiling in allopurinol-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) patients and identify the DNA methylation signature for predisposing allopurinol hypersensitivity.

METHODS

Genome-scale methylation analysis was conducted using the Illumina HumanMethylation450 BeadChip. Weighted Gene Co-Expression Network Analysis (WGCNA) was utilized to analyze the data.

RESULTS

A total of 21,497 annotated promoter regions were analyzed. Ten modules were identified between allopurinol hypersensitivity and tolerance, with turquoise and yellow modules being the most significant correlation. ATG13, EPM2AIP1, and SRSF11 were the top three hub genes in the turquoise module. MIR412, MIR369, and MIR409 were the top three hub genes in the yellow module. Gene Ontology (GO) analysis revealed that the turquoise module was related to the metabolic process in intracellular organelles and the binding of various compounds, proteins, or nucleotides. The yellow module, however, was related to stimulus sensory perception in cytoskeletal elements and the activity of the receptor or transducer.

CONCLUSION

DNA methylation plays a vital role in allopurinol-induced SCARs. DNA methylation profiling of SJS/TEN is significantly related to autophagy and microRNAs (miRNAs).

摘要

背景

异常DNA甲基化在别嘌醇诱导的严重皮肤不良反应（SCARs）中的作用尚未完全明确。为填补这一空白，我们分析了别嘌醇诱导的史蒂文斯-约翰逊综合征（SJS）和中毒性表皮坏死松解症（TEN）患者的DNA甲基化谱，并确定了易患别嘌醇超敏反应的DNA甲基化特征。

方法

使用Illumina HumanMethylation450 BeadChip进行全基因组甲基化分析。利用加权基因共表达网络分析（WGCNA）对数据进行分析。

结果

共分析了21,497个注释的启动子区域。在别嘌醇超敏反应和耐受性之间鉴定出10个模块，其中蓝绿色和黄色模块的相关性最为显著。ATG13、EPM2AIP1和SRSF11是蓝绿色模块中的前三个枢纽基因。MIR412、MIR369和MIR409是黄色模块中的前三个枢纽基因。基因本体（GO）分析显示，蓝绿色模块与细胞内细胞器的代谢过程以及各种化合物、蛋白质或核苷酸的结合有关。然而，黄色模块与细胞骨架元件中的刺激感觉感知以及受体或转导器的活性有关。

结论

DNA甲基化在别嘌醇诱导的SCARs中起着至关重要的作用。SJS/TEN的DNA甲基化谱与自噬和微小RNA（miRNA）显著相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cea1/9027774/7afee95b8fd3/jpm-12-00525-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cea1/9027774/30ce6f67ba9f/jpm-12-00525-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cea1/9027774/5c937ac3d806/jpm-12-00525-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cea1/9027774/a625c4fa43cf/jpm-12-00525-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cea1/9027774/7afee95b8fd3/jpm-12-00525-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cea1/9027774/30ce6f67ba9f/jpm-12-00525-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cea1/9027774/5c937ac3d806/jpm-12-00525-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cea1/9027774/a625c4fa43cf/jpm-12-00525-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cea1/9027774/7afee95b8fd3/jpm-12-00525-g004.jpg

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