非甾体抗炎药诱导的呼吸系统疾病患者外周血淋巴细胞的全基因组DNA甲基化谱

IF 1.7 3区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Jong-Uk Lee, Hun Soo Chang, Min Kyung Kim, Seung-Lee Park, Jung Hyun Kim, Jong-Sook Park, Choon-Sik Park
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引用次数: 1

摘要

背景:CpG甲基化在鼻息肉中有显著变化,鼻息肉是非甾体抗炎药加重呼吸系统疾病(NERD)的主要靶点;然而,这些息肉是由各种细胞成分组成的。本研究分析了外周血淋巴细胞(pbl)全基因组CpG甲基化,以确定淋巴细胞的表观遗传变化,淋巴细胞是参与NERD的主要免疫细胞。材料和方法:对27例NERD和24例阿斯匹林耐受性哮喘(ATA)患者外周血单个核细胞的基因组DNA进行硫酸氢盐转化和甲基化阵列。在调整细胞组成后,计算淋巴细胞中定量CpG甲基化,即作为DNA甲基化定量测量的β值。结果:与ATA相比,NERD患者pbl中56个高甲基化CpGs和3个低甲基化差异甲基化CpGs (DMCs)。前10个CpG位点预测甲基化风险评分,阳性预测值为91.3%,阴性预测值为81.5%,准确率为84.3%。如鼻息肉中所示,预计有30个DMCs与以下10个转录因子结合,按降序排列:ap -2alpha、TFII-1、STAT4、FOXP3、GR、c-Est-1、E2F-1、XBP1、ENKTF-1和NF-1。基因本体论分析确定了13个类别,如调节t -辅助性17细胞分化,包括SMAD7和NFKBIZ。NERD的pbl不含与前列腺素和白三烯通路相关的基因dmc,而这些基因在ATA中发现。结论:NERD的pbl形成独特的DNA CpG甲基化模式,联合分析可为NERD提供预测价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genome-wide DNA methylation profile of peripheral blood lymphocytes from subjects with nonsteroidal anti-inflammatory drug-induced respiratory diseases.

Background: Significant changes in CpG methylation have been identified in nasal polyps, which are the main targets of nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NERD); however, these polyps are composed of various cellular components. In the present study, whole-genome CpG methylation in peripheral blood lymphocytes (PBLs) was analyzed to define the epigenetic changes in lymphocytes, which are the primary immune cells involved in NERD.

Materials and methods: Genomic DNA from peripheral blood mononuclear cells from 27 NERD and 24 aspirin-tolerant asthma (ATA) was subjected to bisulfate conversion and a methylation array. Quantitative CpG methylation, the β-values as a quantitative measure of DNA methylation, in lymphocytes were calculated after adjustments for cellular composition.

Results: Fifty-six hypermethylated and three hypomethylated differentially methylated CpGs (DMCs) in PBLs in the NERD compared with ATA. The top 10 CpG loci predicted the methylation risk score, with a positive predictive value of 91.3%, a negative predictive value of 81.5% and an accuracy of 84.3%. As demonstrated in the nasal polyps, 30 DMCs were predicted to bind to the following 10 transcription factors, ranked in descending order: AP-2alphaA, TFII-1, STAT4, FOXP3, GR, c-Est-1, E2F-1, XBP1, ENKTF-1 and NF-1. Gene ontology analysis identified 13 categories such as regulation of T-helper 17 cell differentiation, including SMAD7 and NFKBIZ. PBLs in NERD contained no DMCs in genes associated with the prostaglandin and leukotriene pathways, which were found in ATA.

Conclusion: PBLs in NERD form a unique pattern of DNA CpG methylation, and the combined analysis may provide predictive values for NERD.

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来源期刊
Pharmacogenetics and genomics
Pharmacogenetics and genomics 医学-生物工程与应用微生物
CiteScore
3.20
自引率
3.80%
发文量
47
审稿时长
3 months
期刊介绍: ​​​​Pharmacogenetics and Genomics is devoted to the rapid publication of research papers, brief review articles and short communications on genetic determinants in response to drugs and other chemicals in humans and animals. The Journal brings together papers from the entire spectrum of biomedical research and science, including biochemistry, bioinformatics, clinical pharmacology, clinical pharmacy, epidemiology, genetics, genomics, molecular biology, pharmacology, pharmaceutical sciences, and toxicology. Under a single cover, the Journal provides a forum for all aspects of the genetics and genomics of host response to exogenous chemicals: from the gene to the clinic.
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